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Sample records for characterize diet-induced obese

  1. Leptin resistance: a prediposing factor for diet-induced obesity

    OpenAIRE

    Scarpace, Philip J.; Zhang, Yi

    2008-01-01

    Obesity is a resilient and complex chronic disease. One potential causative factor in the obesity syndrome is leptin resistance. Leptin behaves as a potent anorexic and energy-enhancing hormone in most young or lean animals, but its effects are diminished or lacking in the obese state associated with a normal genetic background. Emerging evidence suggests that leptin resistance predisposes the animal to exacerbated diet-induced obesity (DIO). Elevation of central leptin in young, lean rats in...

  2. PTPRT Regulates High-Fat Diet-Induced Obesity and Insulin Resistance

    OpenAIRE

    Feng, Xiujing; Scott, Anthony; Wang, Yong; Wang, Lan; Zhao, Yiqing; Doerner, Stephanie; Satake, Masanobu; Croniger, Colleen M.; Wang, Zhenghe

    2014-01-01

    Obesity is a risk factor for many human diseases. However, the underlying molecular causes of obesity are not well understood. Here, we report that protein tyrosine phosphatase receptor T (PTPRT) knockout mice are resistant to high-fat diet-induced obesity. Those mice avoid many deleterious side effects of high-fat diet-induced obesity, displaying improved peripheral insulin sensitivity, lower blood glucose and insulin levels. Compared to wild type littermates, PTPRT knockout mice show reduce...

  3. Scavenger Receptor CD36 Expression Contributes to Adipose Tissue Inflammation and Cell Death in Diet-Induced Obesity

    OpenAIRE

    Lei CAI; Wang, Zhen; Ji, Ailing; Meyer, Jason M.; van der Westhuyzen, Deneys R.

    2012-01-01

    Objective The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. Experimental Approach Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for ...

  4. Scavenger Receptor CD36 Expression Contributes to Adipose Tissue Inflammation and Cell Death in Diet-Induced Obesity

    OpenAIRE

    Lei Cai; Zhen Wang; Ailing Ji; Meyer, Jason M.; Deneys R. van der Westhuyzen

    2012-01-01

    OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) fo...

  5. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats

    OpenAIRE

    Deblon, Nicolas; Veyrat-Durebex, Christelle; Bourgoin, Lucie; Caillon, Aurélie; Bussier, Anne-Lise; Petrosino, Stefania; Piscitelli, Fabiana; Legros, Jean-Jacques; Geenen, Vincent; Foti, Michelangelo; Wahli, Walter; Di Marzo, Vincenzo; Rohner-Jeanrenaud, Françoise

    2011-01-01

    Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such benefic...

  6. Reduced Capacity for Fatty Acid Oxidation in Rats with Inherited Susceptibility to Diet-Induced Obesity

    OpenAIRE

    Ji, Hong; Friedman, Mark I.

    2007-01-01

    High-fat, energy-dense diets promote weight gain and obesity in humans and other animals, but the mechanisms underlying such diet-induced obesity remain elusive. To determine whether a reduced capacity to oxidize fat is involved in the etiology of diet-induced obesity, we examined different measures of fatty acid oxidation in rats selectively bred for susceptibility (DIO) or resistance (DR) to dietary obesity before and after they were fed a high-fat diet and became obese. DIO rats eating a l...

  7. Effects of Diet-Induced Obesity on Motivation and Pain Behavior in an Operant Assay

    OpenAIRE

    Rossi, Heather L.; Luu, Anthony K.S.; Kothari, Sunny D.; Kuburas, Adisa; Neubert, John K.; Caudle, Robert M.; Recober, Ana

    2013-01-01

    Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in th...

  8. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats.

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    Nicolas Deblon

    Full Text Available Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.

  9. Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

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    Supaporn Wannasiri

    2016-01-01

    Conclusions: To the best of our knowledge, the present study is the first report on the impact of R. nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

  10. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity

    Science.gov (United States)

    The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid tran...

  11. Altered Microbiota Contributes to Reduced Diet-Induced Obesity upon Cold Exposure.

    Science.gov (United States)

    Ziętak, Marika; Kovatcheva-Datchary, Petia; Markiewicz, Lidia H; Ståhlman, Marcus; Kozak, Leslie P; Bäckhed, Fredrik

    2016-06-14

    Maintenance of body temperature in cold-exposed animals requires induction of thermogenesis and management of fuel. Here, we demonstrated that reducing ambient temperature attenuated diet-induced obesity (DIO), which was associated with increased iBAT thermogenesis and a plasma bile acid profile similar to that of germ-free mice. We observed a marked shift in the microbiome composition at the phylum and family levels within 1 day of acute cold exposure and after 4 weeks at 12°C. Gut microbiota was characterized by increased levels of Adlercreutzia, Mogibacteriaceae, Ruminococcaceae, and Desulfovibrio and reduced levels of Bacilli, Erysipelotrichaceae, and the genus rc4-4. These genera have been associated with leanness and obesity, respectively. Germ-free mice fed a high-fat diet at room temperature gained less adiposity and improved glucose tolerance when transplanted with caecal microbiota of mice housed at 12°C compared to mice transplanted with microbiota from 29°C. Thus, a microbiota-liver-BAT axis may mediate protection against obesity at reduced temperature. PMID:27304513

  12. Targeting the Microbiota to Address Diet-Induced Obesity: A Time Dependent Challenge

    OpenAIRE

    Clarke, Siobhan F.; Murphy, Eileen F.; O’Sullivan, Orla; Ross, R Paul; O’Toole, Paul W; Shanahan, Fergus; Cotter, Paul D.

    2013-01-01

    Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO) mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac+), with metabolic improvement ac...

  13. Hypoglycemic effects of brassinosteroid in diet-induced obese mice

    OpenAIRE

    Esposito, Debora; Kizelsztein, Pablo; Komarnytsky, Slavko; Raskin, Ilya

    2012-01-01

    The prevalence of obesity is increasing globally, and obesity is a major risk factor for metabolic diseases such as type 2 diabetes. Previously, we reported that oral administration of homobrassinolide (HB) to healthy rats triggered a selective anabolic response that was associated with lower blood glucose. Therefore, the aim of this study was to evaluate the effects of HB administration on glucose metabolism, insulin sensitivity, body composition, and gluconeogenic gene expression profiles i...

  14. Effects of diet-induced obesity on motivation and pain behavior in an operant assay.

    Science.gov (United States)

    Rossi, H L; Luu, A K S; Kothari, S D; Kuburas, A; Neubert, J K; Caudle, R M; Recober, A

    2013-04-01

    Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet (RD) and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in this assay were strain and reward dependent. Obesity-prone C57BL/6J mice fed a high-fat diet (HFD) display lower number of licks of a caloric, palatable reward (33% sweetened condensed milk or 30% sucrose) than control mice. This occurred at all temperatures, in both sexes, and was evident even before the onset of obesity. This diminished reward-seeking behavior was not observed in obesity-resistant SKH1-E (SK) mice. These findings suggest that diet and strain interact to modulate reward-seeking behavior. Furthermore, we observed a difference between diet groups in operant behavior with caloric, palatable rewards, but not with a non-caloric neutral reward (water). Importantly, we found no effect of diet-induced obesity on acute thermal nociception in the absence of inflammation or injury. This indicates that thermal sensation in the face is not affected by obesity-associated peripheral neuropathy as it occurs when studying pain behaviors in the rodent hindpaw. Future studies using this model may reveal whether obesity facilitates the development of chronic pain after injury or inflammation. PMID:23333672

  15. Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice

    OpenAIRE

    Pini, Maria; Rhodes, Davina H.; Fantuzzi, Giamila

    2011-01-01

    Obesity is associated with chronic inflammation and elevated levels of IL-6. The role of IL-6 in induction of acute-phase proteins and modulation of haematological responses has been demonstrated in models of inflammation and aging, but not in obesity. We hypothesized that IL-6 is necessary to regulate the acute-phase response and hematological changes associated with diet-induced obesity (DIO) in mice. Feeding a 60% kcal/fat diet for 13 weeks to C57BL6 WT male mice induced a significant incr...

  16. Serotonin Improves High Fat Diet Induced Obesity in Mice.

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    Hitoshi Watanabe

    Full Text Available There are two independent serotonin (5-HT systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

  17. Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Lei Cai

    Full Text Available OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO mice and wild type (WT mice fed a high fat diet (60% kcal fat for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice. RESULTS: Compared to WT mice, CD36 KO mice fed a high fat diet exhibited reduced adiposity and adipose tissue inflammation, with decreased adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T-cell accumulation. In primary cell culture, the absence of CD36 expression in macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene expression in response to lipopolysaccharide (LPS. Likewise, CD36 deficiency in primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in response to LPS. Primary macrophage and adipocyte co-culture experiments showed that these cell types act synergistically in their inflammatory response to LPS and that CD36 modulates such synergistic effects. CONCLUSIONS: CD36 enhances adipose tissue inflammation and cell death in diet-induced obesity through its expression in both macrophages and adipocytes.

  18. Sexually dimorphic myeloid inflammatory and metabolic responses to diet-induced obesity.

    Science.gov (United States)

    Griffin, C; Lanzetta, N; Eter, L; Singer, K

    2016-08-01

    It is well known in clinical and animal studies that women and men have different disease risk as well as different disease physiology. Women of reproductive age are protected from metabolic and cardiovascular disease compared with postmenopausal women and men. Most murine studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of similar protection in female mice. We have investigated dietary obesity in a mouse model and have directly compared inflammatory responses in males and females. In this review we will summarize what is known about sex differences in diet-induced inflammation and will summarize our data on this topic. It is clear that sex differences in high-fat diet-induced inflammatory activation are due to cell intrinsic differences in hematopoietic responses to obesogenic cues, but further research is needed to understand what leads to sexually dimorphic responses. PMID:27252473

  19. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    Science.gov (United States)

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-01-01

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese. PMID:27271106

  20. MyD88 signaling in the CNS is required for development of fatty acid induced leptin resistance and diet-induced obesity

    OpenAIRE

    Kleinridders, Andre; Schenten, Dominik; Mauer, Jan; Wunderlich, F. Thomas; Okamura, Tomoo; Koenner, A. Christine; Belgardt, Bengt F.; Bruening, Jens C.; Medzhitov, Ruslan

    2009-01-01

    Obesity-associated activation of inflammatory pathways represents a key step in the development of insulin resistance in peripheral organs, partially via activation of TLR-4 signaling by fatty acids. Here we demonstrate that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat-3 activation. To determine the functional significance of TLR signaling in the CNS in the development of leptin resistance and diet-induced obesity in vivo, we have characterize...

  1. Effect of Coleus forskohliiextract on cafeteria diet-induced obesity in rats

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    Hebbani Nagarajappa Shivaprasad

    2014-01-01

    Full Text Available Background: Obesity is a metabolic disorder that can lead to adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance and also increases the risk of coronary heart disease, ischemic stroke and type 2 diabetes mellitus. This study was designed to determine the effect of Coleus forskohlii on obesity and associated metabolic changes in rats fed with cafeteria diet. Objective: The aim of this study was to evaluate antiobesogenic and metabolic benefits of C. forskohlii in cafeteria diet induced obesity rat model. Materials and Methods: Rats were randomly divided into five groups of six animals in each group and as follows: Normal pellet diet group; cafeteria diet group; cafeteria diet followed by 50 mg/kg/d Coleus forskohlii extract (CFE, 100 mg/kg/d CFE and 45 mg/kg/d orlistat groups, respectively. Indicators of obesity such as food intake, body weight and alteration in serum lipid profiles were studied. Results: Feeding of cafeteria diet induced obesity in rats. Administration of CFE significantly halted increase in food intake and weight gain associated with cafeteria diet. Development of dyslipidemia was also significantly inhibited. Conclusion: The observed effects validate that supplementation of CFE with cafeteria diet could curb the appetite and mitigate the development of dyslipidemia.

  2. Cinnamomum camphora Seed Kernel Oil Ameliorates Oxidative Stress and Inflammation in Diet-Induced Obese Rats.

    Science.gov (United States)

    Fu, Jing; Zeng, Cheng; Zeng, Zheling; Wang, Baogui; Gong, Deming

    2016-05-01

    Cinnamomum camphora seed kernel oil (CCSKO) was found to reduce body fat deposition and improve blood lipid in both healthy and obese rats. The study was aimed to investigate the antioxidative stress and anti-inflammatory effects of CCSKO in high-fat-diet-induced obese rats. The obese rats were treated with CCSKO, lard, and soybean oil, respectively, for 12 wk. The level of total antioxidant capacity (T-AOC), activities of superoxide dismutase (SOD), glutathione peroxidase, and catalase, and levels of malondialdehyde (MDA), tumor necrosis factor (TNF)-α, peroxisome proliferator-activated receptor (PPAR)-γ, interleukin (IL)-6, and P65 were compared among CCSKO, lard, and soybean oil groups. Our results showed that the level of T-AOC and activities of SOD and catalase were significantly increased and the level of MDA was significantly decreased in CCSKO group. In addition, CCSKO treatment reduced the activities of serum glutamic oxaloacetic transaminase and glutamate-pyruvate transaminase, and levels of serum TNF-α, IL-6, and P65 through raising the level of PPAR-γ. In conclusion, CCSKO has, for the first time, been found to ameliorate oxidative stress and inflammation in high-fat-diet-induced obese rats. PMID:27003858

  3. Changes in gene expression foreshadow diet-induced obesity in genetically identical mice.

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    Robert A Koza

    2006-05-01

    Full Text Available High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity.

  4. Cafeteria diet-induced obesity causes oxidative damage in white adipose.

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    Johnson, Amy R; Wilkerson, Matthew D; Sampey, Brante P; Troester, Melissa A; Hayes, D Neil; Makowski, Liza

    2016-04-29

    Obesity continues to be one of the most prominent public health dilemmas in the world. The complex interaction among the varied causes of obesity makes it a particularly challenging problem to address. While typical high-fat purified diets successfully induce weight gain in rodents, we have described a more robust model of diet-induced obesity based on feeding rats a diet consisting of highly palatable, energy-dense human junk foods - the "cafeteria" diet (CAF, 45-53% kcal from fat). We previously reported that CAF-fed rats became hyperphagic, gained more weight, and developed more severe hyperinsulinemia, hyperglycemia, and glucose intolerance compared to the lard-based 45% kcal from fat high fat diet-fed group. In addition, the CAF diet-fed group displayed a higher degree of inflammation in adipose and liver, mitochondrial dysfunction, and an increased concentration of lipid-derived, pro-inflammatory mediators. Building upon our previous findings, we aimed to determine mechanisms that underlie physiologic findings in the CAF diet. We investigated the effect of CAF diet-induced obesity on adipose tissue specifically using expression arrays and immunohistochemistry. Genomic evidence indicated the CAF diet induced alterations in the white adipose gene transcriptome, with notable suppression of glutathione-related genes and pathways involved in mitigating oxidative stress. Immunohistochemical analysis indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared to rats that remained lean on control standard chow diet. Our data indicates that the CAF diet drives an increase in oxidative damage in white adipose tissue that may affect tissue homeostasis. Oxidative stress drives activation of inflammatory kinases that can perturb insulin signaling leading to glucose intolerance and diabetes. PMID:27033600

  5. Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity.

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    Souza, Gabriela F P; Solon, Carina; Nascimento, Lucas F; De-Lima-Junior, Jose C; Nogueira, Guilherme; Moura, Rodrigo; Rocha, Guilherme Z; Fioravante, Milena; Bobbo, Vanessa; Morari, Joseane; Razolli, Daniela; Araujo, Eliana P; Velloso, Licio A

    2016-01-01

    Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obesity-linked hypothalamic defect is and how it orchestrates the energy imbalance present in obesity. Using an outbred model of diet-induced obesity we show that defective regulation of hypothalamic POMC is the earliest marker distinguishing obesity-prone from obesity-resistant mice. The early inhibition of hypothalamic POMC was sufficient to transform obesity-resistant in obesity-prone mice. In addition, the post-prandial change in the blood level of β-endorphin, a POMC-derived peptide, correlates with body mass gain in rodents and humans. Taken together, these results suggest that defective regulation of POMC expression, which leads to a change of β-endorphin levels, is the earliest hypothalamic defect leading to obesity. PMID:27373214

  6. Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice.

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    Cao, Jay J; Sun, Li; Gao, Hongwei

    2010-03-01

    Obesity-derived body mass may be detrimental to bone health through not well-defined mechanisms. In this study we determined changes in bone structure and serum cytokines related to bone metabolism in diet-induced obese mice. Mice fed a high-fat diet (HFD) had higher serum tartrate-resistant acid phosphatase (TRAP) and leptin but lower osteocalcin concentrations than those fed the normal-fat diet. The HFD increased multinucleated TRAP-positive osteoclasts in bone marrow compared to the control diet. Despite being much heavier, mice fed the HFD had lower femoral bone volume, trabecular number, and connectivity density and higher trabecular separation than mice on the control diet. These findings suggest that obesity induced by a HFD increases bone resorption that may blunt any positive effects of increased body weight on bone. PMID:20392249

  7. Beneficial Effects of Oolong Tea Consumption on Diet-induced Overweight and Obese Subjects

    Institute of Scientific and Technical Information of China (English)

    HE Rong-rong; CHEN Ling; LIN Bing-hui; MATSUI Yokichi; YAO Xin-sheng; KURIHARA Hiroshi

    2009-01-01

    Objective: To determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity. Methods: A total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects. The body fat level of the subjects was determined at the same time by taking body weight, height and waist measurements. The thickness of the subcutaneous fat layer was also determined on the abdomen 3 cm to the right of the navel by the ultrasonic echo method. On the other hand, effects of oolong tea ingestion on plasma triglyceride (TG) and total cholesterol (TC) were determined. Inhibitions of pancreatic lipase by oolong tea extract and catechins in vitro were also determined. Results: A total of 70% of the severely obese subjects did show a decrease of more than 1 kg in body weight, including 22% who lost more than 3 kg. Similarly, 64% of the obese subjects and 66% of the overweight subjects lost more than 1 kg during the experiment, and the subcutaneous fat content decreased in 12% of the subjects. The correlation between weight loss and subcutaneous fat decrease in men (r=0.055) was obviously lower than that in women (r=0.440, P0.05). Moreover, the plasma levels of TG and TC of the subjects with hyperlipidemia were remarkably decreased after ingesting oolong tea for 6 weeks. In vitro assays for the inhibition of pancreatic lipase by oolong tea extract and catechins suggest that the mechanism for oolong tea to prevent hyperlipidemia may be related to the regulative action of oolong tea catechins in lipoprotein activity. Conclusions: Oolong tea could decrease body fat content and reduce body weight through improving lipid metabolism. Chronic consumption of oolong tea may prevent against obesity.

  8. High-fat-diet-induced obesity causes an inflammatory and tumor-promoting microenvironment in the rat kidney

    OpenAIRE

    Kerstin Stemmer; Diego Perez-Tilve; Gayathri Ananthakrishnan; Anja Bort; Seeley, Randy J.; Tschöp, Matthias H.; Dietrich, Daniel R.; Pfluger, Paul T.

    2012-01-01

    SUMMARY Obesity and concomitant comorbidities have emerged as public health problems of the first order. For instance, obese individuals have an increased risk for kidney cancer. However, direct mechanisms linking obesity with kidney cancer remain elusive. We hypothesized that diet-induced obesity (DIO) promotes renal carcinogenesis by inducing an inflammatory and tumor-promoting microenvironment. We compared chow-fed lean Wistar rats with those that were sensitive (DIOsens) or partially r...

  9. Thrombospondin 1 mediates renal dysfunction in a mouse model of high-fat diet-induced obesity

    OpenAIRE

    Cui, Wenpeng; Maimaitiyiming, Hasiyeti; Qi, Xinyu; Norman, Heather; Wang, Shuxia

    2013-01-01

    Obesity is prevalent worldwide and is a major risk factor for many diseases including renal complications. Thrombospondin 1 (TSP1), a multifunctional extracellular matrix protein, plays an important role in diabetic kidney diseases. However, whether TSP1 plays a role in obesity-related kidney disease is unknown. In the present studies, the role of TSP1 in obesity-induced renal dysfunction was determined by using a diet-induced obese mouse model. The results demonstrated that TSP1 was signific...

  10. A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats

    DEFF Research Database (Denmark)

    Feigh, M; Henriksen, K; Andreassen, K V;

    2011-01-01

    To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes....

  11. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer.

    Science.gov (United States)

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  12. Combined Treatment of Mulberry Leaf and Fruit Extract Ameliorates Obesity-Related Inflammation and Oxidative Stress in High Fat Diet-Induced Obese Mice

    OpenAIRE

    Lim, Hyun Hwa; Yang, Soo Jin; Kim, Yuri; Lee, Myoungsook; LIM, YUNSOOK

    2013-01-01

    The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1...

  13. Spatial disturbances in altered mucosal and luminal gut viromes of diet-induced obese mice.

    Science.gov (United States)

    Kim, Min-Soo; Bae, Jin-Woo

    2016-05-01

    Gut microbial biogeography is a key feature of host-microbe relationships. In gut viral ecology, biogeography and responses to dietary intervention remain poorly understood. Here, we conducted a metagenomic study to determine the composition of the mucosal and luminal viromes of the gut and to evaluate the impact of a Western diet on gut viral ecology. We found that mucosal and luminal viral assemblages comprised predominantly temperate phages. The mucosal virome significantly differed from the luminal virome in low-fat diet-fed lean mice, where spatial variation correlated with bacterial microbiota from the mucosa and lumen. The mucosal and luminal viromes of high-fat, high-sucrose 'Western' diet-fed obese mice were significantly enriched with temperate phages of the Caudovirales order. Interestingly, this community alteration occurred to a greater extent in the mucosa than lumen, leading to loss of spatial differences; however, these changes recovered after switching to a low-fat diet. Temperate phages enriched in the Western diet-induced obese mice were associated with the Bacilli, Negativicutes and Bacteroidia classes and temperate phages from the Bacteroidia class particularly encoded stress and niche-specific functions advantageous to bacterial host adaptation. This study illustrates a biogeographic view of the gut virome and phage-bacterial host connections under the diet-induced microbial dysbiosis. PMID:26690305

  14. Hydrolyzed casein reduces diet-induced obesity in male C57BL/6J mice

    DEFF Research Database (Denmark)

    Lillefosse, Haldis Haukås; Tastesen, Hanne Sørup; Du, Zhen-Yu;

    2013-01-01

    The digestion rate of dietary protein is a regulating factor for postprandial metabolism both in humans and animal models. However, few data exist about the habitual consumption of proteins with different digestion rates with regard to the development of body mass and diet-induced obesity. Here, we...... used a factorial ANOVA design to investigate the effects of protein form (intact vs. hydrolyzed casein) and protein level (16 vs. 32 energy percent protein) on body mass gain and adiposity in obesity-prone male C57BL/6J mice fed Western diets with 35 energy percent fat. Mice fed the hydrolyzed casein...... diets had higher spontaneous locomotor activity than mice fed intact casein. During the light phase, mice fed hydrolyzed casein tended (P = 0.08) to have a lower respiratory exchange ratio, indicating lower utilization of carbohydrates as energy substrate relative to those fed intact casein. In further...

  15. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C., E-mail: susan.tilton@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Lee, K. Monica [Battelle Toxicology Northwest, Richland, WA 99352 (United States); Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung

  16. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    International Nuclear Information System (INIS)

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung

  17. Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

    OpenAIRE

    Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, urs...

  18. Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats

    OpenAIRE

    Betik, Andrew C.; Aguila, Jay; McConell, Glenn K.; McAinch, Andrew J.; Michael L. Mathai

    2016-01-01

    Background and Aims Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9)...

  19. Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, Monika K.; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  20. Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

    Directory of Open Access Journals (Sweden)

    Siobhan F Clarke

    Full Text Available Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac(+, with metabolic improvement achieved in DIO mice in receipt of vancomycin. However, two phases of weight gain were observed with effects most marked early in the intervention phase. Here, we compare the gut microbial populations at the early relative to the late stages of intervention using a high throughput sequencing-based analysis to understand the temporal relationship between the gut microbiota and obesity. This reveals several differences in microbiota composition over the intervening period. Vancomycin dramatically altered the gut microbiota composition, relative to controls, at the early stages of intervention after which time some recovery was evident. It was also revealed that Bac(+ treatment initially resulted in the presence of significantly higher proportions of Peptococcaceae and significantly lower proportions of Rikenellaceae and Porphyromonadaceae relative to the gut microbiota of L. salivarius UCC118 bacteriocin negative (Bac(- administered controls. These differences were no longer evident at the later time. The results highlight the resilience of the gut microbiota and suggest that interventions may need to be monitored and continually adjusted to ensure sustained modification of the gut microbiota.

  1. Popular edible seaweed, Gelidium amansii prevents against diet-induced obesity.

    Science.gov (United States)

    Kang, Min-Cheol; Kang, Nalae; Kim, Seo-Young; Lima, Inês S; Ko, Seok-Chun; Kim, Young-Tae; Kim, Young-Bum; Jeung, Hee-Do; Choi, Kwang-Sik; Jeon, You-Jin

    2016-04-01

    The popular edible seaweed, Gelidium amansii is broadly used as food worldwide. To determine whether G. amansii extract (GAE) has protective effects on obesity, mice fed a high-fat diet (HFD) treated with GAE (1 and 3 %) were studied. After 12 weeks of GAE treatment, body weight was greatly decreased in mice fed a high-fat diet. This effect could be due to decreased adipogenesis, as evidenced by the fact that GAE suppressed adipogenic gene expression in adipocytes. In addition, blood glucose and serum insulin levels were reduced by GAE treatment in mice fed a high-fat diet, suggesting improvement in glucose metabolism. GAE supplementation also led to a significant decrease in total cholesterol and triglyceride levels. These data are further confirmed by H&E staining. Our findings indicate that Gelidium amansii prevents against the development of diet-induced obesity, and further implicate that GAE supplementation could be the therapeutical option for treatment of metabolic disorder such as obesity. PMID:26911551

  2. Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents.

    Science.gov (United States)

    Igarashi, Miki; DiPatrizio, Nicholas V; Narayanaswami, Vidya; Piomelli, Daniele

    2015-09-01

    The gastrointestinal tract plays a critical role in the regulation of energy homeostasis by initiating neural and hormonal responses to the ingestion of nutrients. In addition to peptide hormones, such as cholecystokinin (CKK) and peptide YY (PYY), the lipid-derived mediator oleoylethanolamide (OEA) has been implicated in the control of satiety. Previous studies in humans and rodent models have shown that obesity is associated with changes in CCK, PYY and other gut-derived peptide hormones, which may contribute to decreased satiety and increased energy intake. In the present study, we show that small-intestinal OEA production is disrupted in the gut of diet-induced obese (DIO) rats and mice. In lean rodents, feeding or duodenal infusion of Intralipid® or pure oleic acid stimulates jejunal OEA mobilization. This response is strikingly absent in DIO rats and mice. Confirming previous reports, we found that feeding rats or mice a high-fat diet for 7 days is sufficient to suppress jejunal OEA mobilization. Surprisingly, a similar effect is elicited by feeding rats and mice a high-sucrose low-fat diet for 7 days. Collectively, our findings suggest that high fat-induced obesity is accompanied by alterations in the post-digestive machinery responsible for OEA biosynthesis, which may contribute to reduced satiety and hyperphagia. PMID:26024927

  3. Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    Supaporn Wannasiri; Pritsana Piyabhan; Jarinyaporn Naowaboot

    2016-01-01

    Objective: To investigate the effect of Rhinacanthus nasutus (R. nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice. Methods: Obesity was induced in the male ICR mice by feeding them a high-fat diet (60 kcal% fat) for 12 weeks. After the first six weeks of the diet, the obese mice were administered with the water extract of R. nasutus leaves at 250 and 500 mg/kg per day for the next six weeks. Subsequently, the blood glucose, lipid profiles, insulin, leptin, and adiponectin levels were measured. The liver and adipose tissues were excised for his-topathological examination and protein expression study. Results: After six weeks of the treatment, R. nasutus extract (at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level, improve the insulin sensitivity, decrease the serum leptin, and increase the serum adiponectin levels. The obese mice treated with R. nasutus were found to have a reduction in the increased lipid concen-trations in their serum and liver tissues. Moreover, treatment with R. nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues. Interestingly, the administration with R. nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha, fat cell adiponectin, and glucose transporter 4 proteins. Conclusions: To the best of our knowledge, the present study is the first report on the impact of R. nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

  4. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles.

    Science.gov (United States)

    Xue, Yuan; Xu, Xiaoyang; Zhang, Xue-Qing; Farokhzad, Omid C; Langer, Robert

    2016-05-17

    The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. PMID:27140638

  5. Subcutaneous adipose tissue transplantation in diet-induced obese mice attenuates metabolic dysregulation while removal exacerbates it

    OpenAIRE

    Foster, Michelle T.; Softic, Samir; Caldwell, Jody; Kohli, Rohit; deKloet, Annette D; Seeley, Randy J.

    2013-01-01

    Adipose tissue distribution is an important determinant of obesity-related comorbidities. It is well established that central obesity (visceral adipose tissue accumulation) is a risk factor for many adverse health consequences such as dyslipidemia, insulin resistance, and type-2-diabetes. We hypothesize that the metabolic dysregulation that occurs following high fat diet-induced increases in adiposity are due to alterations in visceral adipose tissue function which influence lipid flux to the...

  6. Pro-opiomelanocortin Gene Transfer to the NTS but not ARC Ameliorates Chronic Diet-Induced Obesity

    OpenAIRE

    Zhang, Y.; Rodrigues, E.; Gao, Y.X.; King, M.; Cheng, K. Y.; Erdös, B.; Tümer, N.; Carter, C; Scarpace, P. J.

    2010-01-01

    Short-term pharmacological melanocortin activation deters diet-induced obesity (DIO) effectively in rodents. However, whether central pro-opiomelanocortin (POMC) gene transfer targeted to the hypothalamus or hindbrain nucleus of the solitary track (NTS) can combat chronic dietary obesity has not been investigated. Four-week-old Sprague Dawley rats were fed a high fat diet for five months, and then injected with either the POMC or control vector into the hypothalamus or NTS, and body weight an...

  7. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats

    OpenAIRE

    Lee Si; Cha Min; Kim Jung; Lee Do; Park Shin; An Hyang; Lim Hyung; Kim Kyung; Ha Nam

    2011-01-01

    Abstract Background Recent studies have reported the preventive effects of probiotics on obesity. Among commensal bacteria, bifidobacteria is one of the most numerous probiotics in the mammalian gut and are a type of lactic acid bacteria. The aim of this study was to assess the antiobesity and lipid-lowering effects of Bifidobacterium spp. isolated from healthy Korean on high fat diet-induced obese rats. Methods Thirty-six male Sprague-Dawley rats were divided into three groups as follows: (1...

  8. Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice.

    Science.gov (United States)

    Zhang, Yanqiao; Ge, Xuemei; Heemstra, Lydia A; Chen, Wei-Dong; Xu, Jiesi; Smith, Joseph L; Ma, Huiyan; Kasim, Neda; Edwards, Peter A; Novak, Colleen M

    2012-02-01

    Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr(-/-) mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr(-/-)) mice, the Ldlr(-/-)Fxr(-/-) double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr(-/-) background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr(-/-) mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr(-/-) mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob(-/-)Fxr(-/-) mice that were deficient in both Leptin and Fxr. On a chow diet, ob(-/-)Fxr(-/-) mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob(-/-)Fxr(-/-) mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions. PMID:22261820

  9. Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

    OpenAIRE

    Palmnäs, Marie S. A.; Cowan, Theresa E.; Bomhof, Marc R.; Su, Juliet; Reimer, Raylene A.; Vogel, Hans J.; Hittel, Dustin S.; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, ...

  10. Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats.

    Science.gov (United States)

    Novak, Colleen M; Kotz, Catherine M; Levine, James A

    2006-02-01

    Nonexercise activity thermogenesis (NEAT), the most variable component of energy expenditure, can account for differential capacities for human weight gain. Also highly variable, spontaneous physical activity (SPA) may similarly affect weight balance in animals. In the following study, we utilized the rat model of obesity, the diet-induced obese (DIO) rat, as well as the diet-resistant (DR) rat strain, to investigate how access to a high-fat diet alters SPA and the associated energy expenditure (i.e., NEAT). DIO and DR rats showed no differences in the amount of SPA before access to the high-fat diet. After 29 days on a high-fat diet, the DIO rats showed significant decreases in SPA, whereas the DR rats did not. Next, we wanted to determine whether the DIO and DR rats showed differential sensitivity to microinjections of orexin into the paraventricular nucleus of the hypothalamus (PVN). Unilateral guide cannulae were implanted, aimed at the PVN. Orexin A (0, 0.125, 0.25, and 1.0 nmol in 500 nl) was microinjected through the guide cannula into the PVN, then SPA and energy expenditure were measured for 2 h. Using the response to vehicle as a baseline, the DR rats showed significantly greater increase in NEAT compared with the DIO rats. These data indicate that diet-induced obesity is associated with decreases in SPA and a lack of increase in NEAT. A putative mechanism for changes in NEAT that accompany obesity is a decreased sensitivity to the NEAT-activating effects of neuropeptides such as orexin. PMID:16188908

  11. Phlorizin Supplementation Attenuates Obesity, Inflammation, and Hyperglycemia in Diet-Induced Obese Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Su-Kyung Shin

    2016-02-01

    Full Text Available Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w, high-fat diet (HFD, 20% fat, w/w, or HFD supplemented with phlorizin (PH, 0.02%, w/w. The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon-γ, and interleukin-6, and prevented HFD-induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance.

  12. Elevated IgG levels against specific bacterial antigens in obese patients with diabetes and in mice with diet-induced obesity and glucose intolerance.

    Science.gov (United States)

    Mohammed, Nadeem; Tang, Lihua; Jahangiri, Anisa; de Villiers, Willem; Eckhardt, Erik

    2012-09-01

    High fat diets increase the risk for insulin resistance by promoting inflammation. The cause of inflammation is unclear, but germfree mouse studies have implicated commensal gut bacteria. We tested whether diet-induced obesity, diabetes, and inflammation are associated with anti-bacterial IgG. Blood from lean and obese healthy volunteers or obese patients with diabetes were analyzed by ELISA for IgG against extracts of potentially pathogenic and pro-biotic strains of Escherichia coli (LF-82 and Nissle), Bacteroides thetaiotaomicron, and Lactobacillus acidophilus, and for circulating tumor necrosis factor α (TNFα). C57Bl/6 mice were fed low- or high-fat diets (10% or 60% kcal from fat) for 10 weeks and tested for anti-bacterial IgG, bodyweight, fasting glucose, and inflammation. Obese diabetic patients had significantly more IgG against extracts of E. coli LF-82 compared with lean controls, whereas IgG against extracts of the other bacteria was unchanged. Circulating TNFα was elevated and correlated with IgG against the LF-82 extract. Mice fed high-fat diets had increased fasting glucose levels, elevated TNFα and neutrophils, and significantly more IgG against the LF-82 extracts. Diabetes in obesity is characterized by increased IgG against specific bacterial antigens. Specific commensal bacteria may mediate inflammatory effects of high-fat diets. PMID:22424821

  13. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity.

    Science.gov (United States)

    Kraus, Daniel; Yang, Qin; Kong, Dong; Banks, Alexander S; Zhang, Lin; Rodgers, Joseph T; Pirinen, Eija; Pulinilkunnil, Thomas C; Gong, Fengying; Wang, Ya-chin; Cen, Yana; Sauve, Anthony A; Asara, John M; Peroni, Odile D; Monia, Brett P; Bhanot, Sanjay; Alhonen, Leena; Puigserver, Pere; Kahn, Barbara B

    2014-04-10

    In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes. Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity. Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue (WAT) from adipose-specific Glut4-knockout or adipose-specific Glut4-overexpressing mice with their respective controls. NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor. Nicotinamide is a precursor of NAD(+), an important cofactor linking cellular redox states with energy metabolism. SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation. Polyamine flux including synthesis, catabolism and excretion, is controlled by the rate-limiting enzymes ornithine decarboxylase (ODC) and spermidine-spermine N(1)-acetyltransferase (SSAT; encoded by Sat1) and by polyamine oxidase (PAO), and has a major role in energy metabolism. We report that NNMT expression is increased in WAT and liver of obese and diabetic mice. Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure. NNMT inhibition increases adipose SAM and NAD(+) levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue. Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism. NNMT inhibition in adipocytes increases oxygen consumption in an ODC-, SSAT- and PAO-dependent manner. Thus, NNMT is a novel regulator of histone methylation, polyamine flux and NAD(+)-dependent SIRT1 signalling, and is a unique and attractive target for treating obesity and type 2 diabetes. PMID

  14. Ghrelin does not modulate angiogenesis in matrigel plug in normal and diet-induced obese mice

    Directory of Open Access Journals (Sweden)

    Zoya Tahergorabi

    2013-01-01

    Full Text Available Background: The reciprocal interaction between adipocytes and angiogenesis is considered as an essential component in the development and expansion of adipose tissue. The aim of this study was to evaluate the effect of ghrelin on angiogenic response using in vivo angiogenesis assay of matrigel plug and its correlation with serum leptin levels in normal and diet-induced obese mice. Materials and Methods: This experimental study has been done on 24 male C57BL/6 mice which were randomly divided into four groups: Normal diet (ND or control, ND + ghrelin, high-fat-diet (HFD or obese and HFD + ghrelin (n = 6/group. Obese and control groups received HFD or standard diet for 14 weeks. Then, growth factor reduced matrigel plug (500 ΅l containing bFGF (basic fibroblast growth factor; 100 ng with or without ghrelin (100 ΅g/kg was injected subcutaneously in the mid-ventral abdominal region of each mice. After 10 days, blood samples were taken and matrigel plugs were removed under anesthesia and angiogenic response was assessed by immunohisochemical staining. Results: HFD significantly increased angiogenesis in matrigel plug as expressed as the number of CD31-positive cells than standard diet (43 ΁ 5 vs. 13 ΁ 2.5 CD31 + cells/field. Ghrelin did not alter angiogenesis in matrigel plug in both obese and control groups. There was a strong positive correlation between the number of CD31-positive cells and serum leptin concentration (r = 0.91. Conclusion: Leptin as an angiogenic factor has a positive correlation with angiogenesis in matrigel plug model of angiogenesis and ghrelin could not alter angiogenesis.

  15. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice.

    Science.gov (United States)

    Keung, Wendy; Ussher, John R; Jaswal, Jagdip S; Raubenheimer, Monique; Lam, Victoria H M; Wagg, Cory S; Lopaschuk, Gary D

    2013-03-01

    Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated what effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice were fed a high-fat diet (60% calories from fat) for 12 weeks to develop insulin resistance. Subsequent treatment of mice for 4 weeks with the carnitine palmitoyltransferase-1 inhibitor, oxfenicine (150 mg/kg i.p. daily), resulted in improved whole-body glucose tolerance and insulin sensitivity. Exercise capacity was increased in oxfenicine-treated mice, which was accompanied by an increased respiratory exchange ratio. In the gastrocnemius muscle, oxfenicine increased pyruvate dehydrogenase activity, membrane GLUT4 content, and insulin-stimulated Akt phosphorylation. Intramyocellular levels of lipid intermediates, including ceramide, long-chain acyl CoA, and diacylglycerol, were also decreased. Our results demonstrate that inhibition of mitochondrial fatty acid uptake improves insulin sensitivity in diet-induced obese mice. This is associated with increased carbohydrate utilization and improved insulin signaling in the skeletal muscle, suggestive of an operating Randle Cycle in muscle. PMID:23139350

  16. Effect of Argyreia speciosa root extract on cafeteria diet-induced obesity in rats

    Directory of Open Access Journals (Sweden)

    Shiv Kumar

    2011-01-01

    Full Text Available Objectives : To evaluate the antiobesity effects of the ethanolic extract of Argyreia speciosa roots in rats fed with a cafeteria diet (CD. Materials and Methods : Obesity was induced in albino rats by feeding them a CD daily for 42 days, in addition to a normal diet. Body weight and food intake was measured initially and then every week thereafter. On day 42, the serum biochemical parameters were estimated and the animals were sacrificed with an overdose of ether. The, liver and parametrial adipose tissues were removed and weighed immediately. The liver triglyceride content was estimated. The influence of the extract on the pancreatic lipase activity was also determined by measuring the rate of release of oleic acid from triolein. Results : The body weight at two-to-six weeks and the final parametrial adipose tissue weights were significantly lowered (P < 0.01 and P < 0.05, respectively in rats fed with the CD with Argyreia speciosa extract 500 mg/kg/day as compared to the CD alone. The extract also significantly reduced (P < 0.01 the serum contents of leptin, total cholesterol, low density lipoprotein (LDL, and triglycerides, which were elevated in rats fed with CD alone. In addition, the extract inhibited the induction of fatty liver with the accumulation of hepatic triglycerides. The extract also showed inhibition of pancreatic lipase activity by using triolein as a substrate. Conclusions : The ethanolic extract of Argyreia speciosa roots produces inhibitory effects on cafeteria diet-induced obesity in rats.

  17. Yellow pea fiber improves glycemia and reduces Clostridium leptum in diet-induced obese rats.

    Science.gov (United States)

    Eslinger, Amanda J; Eller, Lindsay K; Reimer, Raylene A

    2014-08-01

    Numerous studies have demonstrated the impact of functional fibers on gut microbiota and metabolic health, but some less well-studied fibers and/or fractions of foods known to be high in fiber still warrant examination. The aim of this study was to assess the effect of yellow pea-derived fractions varying in fiber and protein content on metabolic parameters and gut microbiota in diet-induced obese rats. We hypothesized that the yellow pea fiber (PF) fraction would improve glycemia and alter gut microbiota. Rats were randomized to 1 of 5 isoenergetic dietary treatments for 6 weeks: (1) control; (2) oligofructose (OFS); (3) yellow PF; (4) yellow pea flour (PFL); or (5) yellow pea starch (PS). Glycemia, plasma gut hormones, body composition, hepatic triglyceride content, gut microbiota, and messenger RNA expression of genes related to hepatic fat metabolism were examined. Pea flour attenuated weight gain compared with control, PF, and PS (P Pea flour, PS, and OFS had significantly lower final percent body fat compared with control. Oligofructose but not the pea fraction diets reduced food intake compared with control (P Pea fiber resulted in lower fasting glucose and glucose area under the curve compared with control. Changes in gut microbiota were fraction specific and included a decrease in Firmicutes (percent) for OFS, PF, and PFL compared with control (P yellow pea-derived fractions are able to distinctly modulate metabolic parameters and gut microbiota in obese rats. PMID:25156790

  18. Interaction of Dietary Composition and PYY Gene Expression in Diet-induced Obesity in Rats

    Institute of Scientific and Technical Information of China (English)

    YANG Nianhong; WANG Chongjian; XU Mingjia; MAO Limei; LIU Liegang; SUN Xiufa

    2005-01-01

    Summary: The interaction of high-fat diet and the peptide YY (PYY) gene expression in diet-induced obesity and the mechanisms which predisposed some individuals to become obese on high-fat diet were explored. Thirty-six male SD rats were randomly divided into high-fat diet group (n=27) and chow fed control group (n=9). After 15 weeks of either a high-fat diet or chew fed diet, the high-fat diet group was subdivided into dietary induced obesity (DIO) and dietary induced obesity resistant (DIR) group according to the final body weight. Then the DIO rats were subdivided into two groups for a 8-week secondary dietary intervention. One of the group was switched to chew fed diet, whereas the other DIO and DIR rats continued on the initial high-fat diet. Weight gain and food intake were measured, food efficiency was calculated, and the concentrations of plasma neuropeptide Y (NPY) and PYY were assayed. Hypothalamic NPY mRNA expression and PYY mRNA expression in ileum and colon was detected by RT-PCR. The results showed that at the end of 15th week, the levels of body weight and caloric intake were significantly higher in DIO group than in DIR or control group (P0.05). The concentration of plasma PYY was significantly higher in DIR group than in DIO and CF group, while no significant difference was found between DIO and CF group (P<0.01). After switching the DIO rats to chow fed diet, their body weight gains were significantly lower than that of the DIO-HF group. The expression of PYY mRNA was increased in DIO-HF/CF rats than in DIO-HF rats, and the expression of hypothalamic NPY mRNA was decreased in DIO-HF/CF rats than in DIO-HF group. It was concluded that both dietary composition and PYY gene expression could potently alter the hypothalamic NPY expression and result in different susceptibility to obese and overeating. The decreased PYY was associated with the increased NPY expression and their predisposal to obese and overeating in rats.

  19. Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity.

    Science.gov (United States)

    Robinson, Mike J F; Burghardt, Paul R; Patterson, Christa M; Nobile, Cameron W; Akil, Huda; Watson, Stanley J; Berridge, Kent C; Ferrario, Carrie R

    2015-08-01

    Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty foods), like the smell of brownies, can elicit craving to eat and increase the amount of food consumed. People who are more susceptible to these motivational effects of food cues may have a higher risk for becoming obese. Further, overconsumption of junk-foods leading to the development of obesity may itself heighten attraction to food cues. Here, we used a model of individual susceptibility to junk-foods diet-induced obesity to determine whether there are pre-existing and/or diet-induced increases in attraction to and motivation for sucrose-paired cues (ie, incentive salience or 'wanting'). We also assessed diet- vs obesity-associated alterations in mesolimbic function and receptor expression. We found that rats susceptible to diet-induced obesity displayed heightened conditioned approach prior to the development of obesity. In addition, after junk-food diet exposure, those rats that developed obesity also showed increased willingness to gain access to a sucrose cue. Heightened 'wanting' was not due to individual differences in the hedonic impact ('liking') of sucrose. Neurobiologically, Mu opioid receptor mRNA expression was lower in striatal 'hot-spots' that generate eating or hedonic impact only in those rats that became obese. In contrast, prolonged exposure to junk-food resulted in cross-sensitization to amphetamine-induced locomotion and downregulation of striatal D2R mRNA regardless of the development of obesity. Together these data shed light on individual differences in behavioral and neurobiological consequences of exposure to junk-food diets and the potential contribution of incentive sensitization in susceptible individuals to greater food cue-triggered motivation. PMID:25761571

  20. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda-Yamahara, Mako [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Kume, Shinji, E-mail: skume@belle.shiga-med.ac.jp [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Koya, Daisuke [Department of Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan); Haneda, Masakzu [Division of Metabolism and Biosystemic Science, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan)

    2015-09-18

    Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

  1. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

    International Nuclear Information System (INIS)

    Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding

  2. Leptin resistance in vagal afferent neurons inhibits cholecystokinin signaling and satiation in diet induced obese rats.

    Directory of Open Access Journals (Sweden)

    Guillaume de Lartigue

    Full Text Available BACKGROUND AND AIMS: The gastrointestinal hormone cholecystokinin (CCK plays an important role in regulating meal size and duration by activating CCK1 receptors on vagal afferent neurons (VAN. Leptin enhances CCK signaling in VAN via an early growth response 1 (EGR1 dependent pathway thereby increasing their sensitivity to CCK. In response to a chronic ingestion of a high fat diet, VAN develop leptin resistance and the satiating effects of CCK are reduced. We tested the hypothesis that leptin resistance in VAN is responsible for reducing CCK signaling and satiation. RESULTS: Lean Zucker rats sensitive to leptin signaling, significantly reduced their food intake following administration of CCK8S (0.22 nmol/kg, i.p., while obese Zucker rats, insensitive to leptin, did not. CCK signaling in VAN of obese Zucker rats was reduced, preventing CCK-induced up-regulation of Y2 receptor and down-regulation of melanin concentrating hormone 1 receptor (MCH1R and cannabinoid receptor (CB1. In VAN from diet-induced obese (DIO Sprague Dawley rats, previously shown to become leptin resistant, we demonstrated that the reduction in EGR1 expression resulted in decreased sensitivity of VAN to CCK and reduced CCK-induced inhibition of food intake. The lowered sensitivity of VAN to CCK in DIO rats resulted in a decrease in Y2 expression and increased CB1 and MCH1R expression. These effects coincided with the onset of hyperphagia in DIO rats. CONCLUSIONS: Leptin signaling in VAN is required for appropriate CCK signaling and satiation. In response to high fat feeding, the onset of leptin resistance reduces the sensitivity of VAN to CCK thus reducing the satiating effects of CCK.

  3. Crosstalk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

    NARCIS (Netherlands)

    Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J.P.; Druart, C.; Bindels, L.B.; Guiot, Y.; Derrien, M.M.N.; Muccioli, G.G.; Delzenne, N.M.; Vos, de W.M.; Cani, P.D.

    2013-01-01

    Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated

  4. Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis

    OpenAIRE

    Preitner, Frederic; Mody, Nimesh; Graham, Timothy E; Peroni, Odile D.; Kahn, Barbara B.

    2009-01-01

    The synthetic retinoid Fenretinide (FEN) increases insulin sensitivity in obese rodents and is in early clinical trials for treatment of insulin resistance in obese humans with hepatic steatosis (46). We aimed to determine the physiological mechanisms for the insulin-sensitizing effects of FEN. Wild-type mice were fed a high-fat diet (HFD) with or without FEN from 4–5 wk to 36–37 wk of age (preventive study) or following 22 wk of HF diet-induced obesity (12 wk intervention study). Retinol-bin...

  5. Effects of liquid konjac on parameters related to obesity in diet-induced obese mice.

    Science.gov (United States)

    Aoe, Seiichiro; Kudo, Haruka; Sakurai, Seiya

    2015-01-01

    Konjac-mannan has been suggested to exert a protective effect against visceral obesity. However, there is little knowledge about the effects of liquid konjac (LK) that is partially alkali gelled. The purpose of the present work was to evaluate the potential beneficial effects of a LK powder on obesity in mice. Male C57BL/6J mice were fed a high-fat diet supplemented with either 2.5 or 5% LK powder for 80 days. Growth parameters, abdominal fat content, serum biochemical markers, and hepatic lipid accumulations were measured. Dietary supplementation with LK resulted in decreased body weight gain and abdominal fat accumulation. Dose-dependent decreases were observed in accumulation of hepatic lipids and serum total cholesterol, leptin, insulin concentrations. The study findings indicated that LK had preventing effect against obesity, including the reduction of abdominal and hepatic lipid accumulation and serum parameters related to obesity. PMID:25832784

  6. Dietary Protein Source and Cyclooxygenase-Inhibition Influence Development of Diet-Induced Obesity, Glucose Homeostasis and Brown Adipose Tissue

    DEFF Research Database (Denmark)

    Aune, Ulrike Liisberg

    -grade inflammation accompanying the increasing adipose mass. In order to investigate the relationship between obesity, inflammation and insulin resistance, we ran an experiment feeding mice a high fat/high sucrose diet supplemented with the antiinflammatory cyclooxygenase-inhibitor, indomethacin. We saw that...... indomethacin prevented diet-induced obesity and glucose intolerance, but not insulin resistance. The development of obesity is largely dependent on an imbalance in energy intake relative to expenditure. Thus, strategies that influence energy utilization is of relevance in anti-obesity treatment. High protein...... striking differences between various protein sources in relation to the development of obesity, insulin resistance and hepatic lipid accumulation. Casein protein, despite being the regular protein source used in experimental diets for rodents, seems to provide strong protection against obesity. This was...

  7. Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity.

    Science.gov (United States)

    Lim, Kyungjoon; Barzel, Benjamin; Burke, Sandra L; Armitage, James A; Head, Geoffrey A

    2016-08-01

    High fat diet (HFD)-induced hypertension in rabbits is neurogenic and caused by the central action of leptin, which is thought to be dependent on activation of α-melanocortin-stimulating hormone (α-MSH) and neuropeptide Y-positive neurons projecting to the dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). However, leptin may act directly in these nuclei. Here, we assessed the contribution of leptin, α-MSH, and neuropeptide Y signaling in the DMH and VMH to diet-induced hypertension. Male New Zealand white rabbits were instrumented with a cannula for drug injections into the DMH or VMH and a renal sympathetic nerve activity (RSNA) electrode. After 3 weeks of an HFD (13.3% fat; n=19), rabbits exhibited higher RSNA, mean arterial pressure (MAP), and heart rate compared with control diet-fed animals (4.2% fat; n=15). Intra-VMH injections of a leptin receptor antagonist or SHU9119, a melanocortin 3/4 receptor antagonist, decreased MAP, heart rate, and RSNA compared with vehicle in HFD rabbits (Pheart rate, and RSNA. We conclude that the VMH is the likely origin of leptin-mediated sympathoexcitation and α-MSH hypersensitivity that contribute to obesity-related hypertension. PMID:27296999

  8. High-oleic peanuts increase diet-induced thermogenesis in overweight and obese men

    Directory of Open Access Journals (Sweden)

    Raquel Duarte Moreira Alves

    2014-05-01

    Full Text Available Background: Evidences suggest that nuts consumption can improve energy metabolism. Purpose: This study aimed to compare the effects of acute ingestion of high-oleic and conventional peanuts on appetite, food intake, and energy metabolism in overweight and obese men. Methods: Seventy one subjects (29.8 ± 2.4 kg/m² were assigned to the groups: control (CT, n = 24; conventional peanuts (CVP, n = 23; high-oleic peanuts (HOP, n = 24. Subjects consumed 56 g of peanuts (CVP and HOP or control biscuits (CT after overnight fasting. Thereafter, energy metabolism was evaluated over 200 minutes, during which diet-induced thermogenesis (DIT and substrate oxidation were analyzed. Appetite sensation was recorded for 3 hours. Statistical analyses were performed using the SAS software considering 5% as the significance level. Results: Postprandial energy expenditure and DIT were significantly higher in HOP than in CVP. Substrate oxidation did not differ between groups. Only HOP presented score below 100 indicating incomplete compensation. CT and CVP showed a complete caloric compensation (scores > 100. Regarding appetite sensation, CVP group felt less "full" than HOP and CT. After 3 hours, satiety score of CVP returned to baseline, whereas HOP and CT remained significantly higher. Hunger scores returned to baseline in CVP and CT and they were maintained significantly lowered in HOP. Conclusion: High-oleic peanuts contributed to higher DIT, higher sensation of fullness and incomplete compensation for energy intake compared to conventional peanuts and may be useful to dietary intervention to reduce body weight.

  9. Flavonoid derivative exerts an antidiabetic effect via AMPK activation in diet-induced obesity mice.

    Science.gov (United States)

    Chen, Ying; Zhang, Chang; Jin, Mei-Na; Qin, Nan; Qiao, Wei; Yue, Xiao-Long; Duan, Hong-Quan; Niu, Wen-Yan

    2016-09-01

    In our previous study, a derivative of tiliroside, 3-O-[(E)-4-(4-ethoxyphenyl)-2-oxobut-3-en-1-yl]kaempferol (Fla-OEt) significantly enhanced glucose consumption in insulin resistant HepG2 cells. This article deals with the antihyperglycemic and antihyperlipidemic effects of Fla-OEt in diet-induced obesity (DIO) mice. Daily administration of Fla-OEt significantly decreased oral glucose tolerance test, intraperitoneal insulin tolerance test and serum lipids. Hyperinsulinemic-euglycemic clamp and the ratio of high-density-lipoprotein/low-density-lipoprotein with Fla-OEt treatment were increased comparing with high-fat diet (HFD) group, so lipid metabolism was improved. Histopathology examination showed that the Fla-OEt restored the damage of adipose tissues and liver in DIO mice. Moreover, compared with HFD group, Fla-OEt treatment significantly increased the phosphorylation of AMPK and ACC in adiposity tissues, liver, and muscles. The mechanism of its action might be the activation of AMPK pathway. It appears that Fla-OEt is worth further study for development as a lead compound for a potential antidiabetic agent. PMID:26511291

  10. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity.

    Directory of Open Access Journals (Sweden)

    Do-Young Park

    Full Text Available OBJECTIVE: To investigate the functional effects of probiotic treatment on the gut microbiota, as well as liver and adipose gene expression in diet-induced obese mice. DESIGN: Male C57BL/6J mice were fed a high-fat diet (HFD for 8 weeks to induce obesity, and then randomized to receive HFD+probiotic (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, n = 9 or HFD+placebo (n = 9 for another 10 weeks. Normal diet (ND fed mice (n = 9 served as non-obese controls. RESULTS: Diet-induced obese mice treated with probiotics showed reduced body weight gain and fat accumulation as well as lowered plasma insulin, leptin, total-cholesterol and liver toxicity biomarkers. A total of 151,061 pyrosequencing reads for fecal microbiota were analyzed with a mean of 6,564, 5,274 and 4,464 reads for the ND, HFD+placebo and HFD+probiotic groups, respectively. Gut microbiota species were shared among the experimental groups despite the different diets and treatments. The diversity of the gut microbiota and its composition were significantly altered in the diet-induced obese mice and after probiotic treatment. We observed concurrent transcriptional changes in adipose tissue and the liver. In adipose tissue, pro-inflammatory genes (TNFα, IL6, IL1β and MCP1 were down-regulated in mice receiving probiotic treatment. In the liver, fatty acid oxidation-related genes (PGC1α, CPT1, CPT2 and ACOX1 were up-regulated in mice receiving probiotic treatment. CONCLUSIONS: The gut microbiota of diet-induced obese mice appears to be modulated in mice receiving probiotic treatment. Probiotic treatment might reduce diet-induced obesity and modulate genes associated with metabolism and inflammation in the liver and adipose tissue.

  11. Positive correlation between serum taurine and adiponectin levels in high-fat diet-induced obesity rats.

    Science.gov (United States)

    You, Jeong Soon; Zhao, Xu; Kim, Sung Hoon; Chang, Kyung Ja

    2013-01-01

    The purpose of this study was to investigate the relationship between serum taurine level and serum adiponectin or leptin levels in high-fat diet-induced obesity rats. Five-week-old male Sprague-Dawley rats were randomly divided into three groups for a period of 8 weeks (normal diet, N group; high-fat diet, HF group; high-fat diet + taurine, HFT group). Taurine was supplemented by dissolving in feed water (3% w/v), and the same amount of distilled water was orally administrated to N and HF groups. In serum, adiponectin level was higher in HFT group compared to HF group. The serum taurine level was negatively correlated with serum total cholesterol (TC) level and positively correlated with serum adiponectin level. These results suggest that dietary taurine supplementation has beneficial effects on total cholesterol and adiponectin levels in high-fat diet-induced obesity rats. PMID:23392875

  12. LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.

    Science.gov (United States)

    Tajan, Mylène; Batut, Aurélie; Cadoudal, Thomas; Deleruyelle, Simon; Le Gonidec, Sophie; Saint Laurent, Céline; Vomscheid, Maëlle; Wanecq, Estelle; Tréguer, Karine; De Rocca Serra-Nédélec, Audrey; Vinel, Claire; Marques, Marie-Adeline; Pozzo, Joffrey; Kunduzova, Oksana; Salles, Jean-Pierre; Tauber, Maithé; Raynal, Patrick; Cavé, Hélène; Edouard, Thomas; Valet, Philippe; Yart, Armelle

    2014-10-21

    LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders

  13. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance

    OpenAIRE

    Su Gao; McMillan, Ryan P.; Qingzhang Zhu; Lopaschuk, Gary D.; Hulver, Matthew W.; Butler, Andrew A

    2015-01-01

    Objective: The peptide hormone adropin regulates fuel selection preferences in skeletal muscle under fed and fasted conditions. Here, we investigated whether adropin treatment can ameliorate the dysregulation of fuel substrate metabolism, and improve aspects of glucose homeostasis in diet-induced obesity (DIO) with insulin resistance. Methods: DIO C57BL/6 mice maintained on a 60% kcal fat diet received five intraperitoneal (i.p.) injections of the bioactive peptide adropin34-76 (450 nmol/k...

  14. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity

    OpenAIRE

    Chao, Pei-Ting; Liang YANG; Aja, Susan; Moran, Timothy H.; Bi, Sheng

    2011-01-01

    Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympa...

  15. Cognitive differences between Sprague-Dawley rats selectively bred for sensitivity or resistance to diet induced obesity.

    Science.gov (United States)

    Gurung, Sunam; Agbaga, Martin-Paul; Myers, Dean A

    2016-09-15

    Epidemiological studies have shown strong correlations between high fat diets, diet-induced obesity and cognitive impairment, primarily focusing on cognitive defects after the onset of obesity. A remaining question is whether cognitive impairment precedes obesity in individuals metabolically prone to diet-induced obesity. The inbred diet-induced obesity sensitive (DIO) and resistant (DR) strains of Sprague-Dawley rats serve as models for human polygenic obesity. DIO rats become overweight on a standard rat chow and have metabolic symptoms similar to overweight humans. We hypothesized that cognitive impairment pre-exists in adult male DIO rats prior to exposure to high fat diet. Male DIO and DR rats were fed a standard rat chow diet from 4 through 20 weeks of age and subjected to the Morris water maze at 12 weeks of age. At 5 and 20 weeks of age, brains of DIO and DR males were examined for indices of inflammation, lipid peroxidation and neuroproliferation. DIO rats showed significant memory impairment on water maze and increased indices of hippocampal inflammation at 20 weeks of age compared to DR rats. At 5 weeks of age, DIO rats exhibited significantly less neural progenitor cell (NPCs) proliferation in the dentate gyrus and increased hippocampal lipid peroxidation compared to DR rats. Therefore, we conclude that DIO rats exhibit early post-weaning indices of hippocampal inflammation, lipid peroxidation and decreased NPC proliferation, as well as impaired hippocampal dependent memory by early adulthood suggesting that inherent metabolic differences predispose the DIO strain to cognitive deficit prior to exposure to high fat diet and/or obesity. PMID:27173431

  16. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality

    Science.gov (United States)

    Boon, Mariëtte R.; van den Berg, Sjoerd A. A.; Wang, Yanan; van den Bossche, Jan; Karkampouna, Sofia; Bauwens, Matthias; De Saint-Hubert, Marijke; van der Horst, Geertje; Vukicevic, Slobodan; de Winther, Menno P. J.; Havekes, Louis M.; Jukema, J. Wouter; Tamsma, Jouke T.; van der Pluijm, Gabri; van Dijk, Ko Willems; Rensen, Patrick C. N.

    2013-01-01

    Background/Aims Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity. Methods and Results High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21°C or 28°C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21°C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28°C. Additionally, BMP7 resulted in extensive ‘browning’ of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia. Conclusion Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to

  17. Fenofibrate (PPARalpha agonist) induces beige cell formation in subcutaneous white adipose tissue from diet-induced male obese mice.

    Science.gov (United States)

    Rachid, Tamiris Lima; Penna-de-Carvalho, Aline; Bringhenti, Isabele; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A; Souza-Mello, Vanessa

    2015-02-15

    Browning is characterized by the formation of beige/brite fat depots in subcutaneous white adipose tissue (sWAT). This study aimed to examine whether the chronic activation of PPARalpha by fenofibrate could induce beige cell depots in the sWAT of diet-induced obese mice. High-fat fed animals presented overweight, insulin resistance and displayed adverse sWAT remodeling. Fenofibrate significantly attenuated these parameters. Treated groups demonstrated active UCP-1 beige cell clusters within sWAT, confirmed through higher gene expression of PPARalpha, PPARbeta, PGC1alpha, BMP8B, UCP-1, PRDM16 and irisin in treated groups. PPARalpha activation seems to be pivotal to trigger browning through irisin induction and UCP-1 transcription, indicating that fenofibrate increased the expression of genes typical of brown adipose tissue (BAT) in the sWAT, characterizing the formation of beige cells. These findings put forward a possible role of PPARalpha as a promising therapeutic for metabolic diseases via beige cell induction. PMID:25576856

  18. Anti-Obese Effect of Glucosamine and Chitosan Oligosaccharide in High-Fat Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Lanlan Huang

    2015-04-01

    Full Text Available Objective: This study is to evaluate the anti-obese effects of glucosamine (GLC and chitosan oligosaccharide (COS on high-fat diet-induced obese rats. Methods: The rats were randomly divided into twelve groups: a normal diet group (NF, a high-fat diet group (HF, Orlistat group, GLC high-, middle-, and low-dose groups (GLC-H, GLC-M, GLC-L, COS1 (COS, number-average molecular weight ≤1000 high-, middle-, and low-dose groups (COS1-H, COS1-M, COS1-L, and COS2 (COS, number-average molecular weight ≤3000 high-, middle-, and low-dose groups (COS2-H, COS2-M, COS2-L. All groups received oral treatment by gavage once daily for a period of six weeks. Results: Rats fed with COS1 gained the least weight among all the groups (P < 0.01, and these rats lost more weight than those treated with Orlistat. In addition to the COS2-H and Orlistat groups, the serum total cholesterol (CHO and low-density lipoprotein cholesterol (LDL-C levels were significantly reduced in all treatment groups compared to the HF group (P < 0.01. The various doses of GLC, COS1 and COS2 reduced the expression levels of PPARγ and LXRα mRNA in the white adipose tissue. Conclusions: The results above demonstrated that GLC, COS1, and COS2 improved dyslipidemia and prevented body weight gains by inhibiting the adipocyte differentiation in obese rats induced by a high-fat diet. Thus, these agents may potentially be used to treat obesity.

  19. Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice

    OpenAIRE

    Zhang, Yanqiao; Ge, Xuemei; Heemstra, Lydia A.; Chen, Wei-Dong; Xu, Jiesi; Smith, Joseph L.; Ma, Huiyan; Kasim, Neda; Edwards, Peter A.; Novak, Colleen M.

    2012-01-01

    Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr−/−) mice, the Ldlr−/−Fxr−/− double-knockout mice were highly resistant to diet-induced obesity, which was associated with increase...

  20. Anti-obesity and cardioprotective effects of cinnamic acid in high fat diet- induced obese rats.

    Science.gov (United States)

    Mnafgui, Kais; Derbali, Amal; Sayadi, Sami; Gharsallah, Neji; Elfeki, Abdelfattah; Allouche, Noureddine

    2015-07-01

    Obesity is a chronic metabolic disorder that is associated with numerous diseases including hyperlipidemia, diabetes mellitus, hypertension, atherosclerosis, cardiovascular disease, and cancer. Cinnamic acid is a phytochemical compound having many biological effects and could be considered for the management of obesity. This study is aimed to assess the possible anti-obesity and cardioprotective properties of cinnamic acid (CA) in high fat diet-fed rats (HFD). Male Wistar rats were divided into 4 groups. They received normal diet, HFD diet, HFD supplemented with fluvastatin (2 mg/kg/day) or cinnamic acid (30 mg/kg/day) for 7 weeks. The results showed an increase in body weight of HFD rats by ~27 % as compared to control group. Moreover, serum lipase activity underwent a significant rise by 103 % which led to an increase in the levels of total cholesterol (T-Ch), triglycerides (TG), LDL-cholesterol in serum of untreated HFD-fed rats. Furthermore, the concentration of leptin and angiotensin-converting enzyme (ACE) activity exhibited remarkable increases in serum of HFD-fed rats as compared to controls. Whereas, the administration of CA to HFD-fed rats improved the body weight gain and serum lipid profile and reverted back near to normal the activities of lipase and ACE. In addition, the echocardiography evidenced that CA is able to protect the aorta and aortic arch and avoided vasoconstriction by increasing their diameters and improved liver steatosis and kidney indices of toxicity. Overall, these results suggest that cinnamic acid exerts anti-obesity and antihypertensive effects through inhibition of lipid digestive enzymes and ACE. PMID:26139902

  1. Female Nur77-deficient mice show increased susceptibility to diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Sonia Perez-Sieira

    Full Text Available Adipose tissue is essential in the regulation of body weight. The key process in fat catabolism and the provision of energy substrate during times of nutrient deprivation or enhanced energy demand is the hydrolysis of triglycerides and the release of fatty acids and glycerol. Nur77 is a member of the NR4A subfamily of nuclear receptors that plays an important metabolic role, modulating hepatic glucose metabolism and lipolysis in muscle. However, its endogenous role on white adipose tissue, as well as the gender dependency of these mechanisms, remains largely unknown. Male and female wild type and Nur77 deficient mice were fed with a high fat diet (45% calories from fat for 4 months. Mice were analyzed in vivo with the indirect calorimetry system, and tissues were analyzed by real-time PCR and Western blot analysis. Female, but not male Nur77 deficient mice, gained more weight and fat mass when compared to wild type mice fed with high fat diet, which can be explained by decreased energy expenditure. The lack of Nur77 also led to a decreased pHSL/HSL ratio in white adipose tissue and increased expression of CIDEA in brown adipose tissue of female Nur77 deficient mice. Overall, these findings suggest that Nur77 is an important physiological modulator of lipid metabolism in adipose tissue and that there are gender differences in the sensitivity to deletion of the Nur77 signaling. The decreased energy expenditure and the actions of Nur77 on liver, muscle, brown and white adipose tissue contribute to the increased susceptibility to diet-induced obesity in females lacking Nur77.

  2. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity.

    Science.gov (United States)

    Gil-Ortega, Marta; Stucchi, Paula; Guzmán-Ruiz, Rocío; Cano, Victoria; Arribas, Silvia; González, M Carmen; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S; Somoza, Beatriz

    2010-07-01

    Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) m) and sodium nitroprusside (10(-12)-10(-5) m) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function. PMID:20410199

  3. Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats

    Institute of Scientific and Technical Information of China (English)

    Shi-ying DING; Zhu-fang SHEN; Yue-teng CHEN; Su-juan SUN; Quan Liu; Ming-zhi XIE

    2005-01-01

    Aim: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR)-γ agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Methods: Normal female Wistar rats were injected intraperitoneally with low-dose streptozotocin (STZ, 30 mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20 mg/kg) was administered orally to the obese and insulin-resistant rats for 28 d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and gluconeogenesis tests were carried out over the last 14 d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression in the liver and skeletal muscle were detected using Western blotting. Results: Significant insulin resistance and obesity were observed in low-dose STZ and high sucrose-fat diet induced obese rats. Pioglitazone (20 mg/kg) treatment significantly decreased serum insulin,triglyceride and free fatty acid levels, and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liver and muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liver and skeletal muscles and the GLUT4 contents in skeletal muscle were elevated significantly. Conclusion: The data suggest that treatment with pioglitazone improves insulin sensitivity in low-dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing effect may be associated with ameliorating lipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.

  4. Nootkatone, a characteristic constituent of grapefruit, stimulates energy metabolism and prevents diet-induced obesity by activating AMPK.

    Science.gov (United States)

    Murase, Takatoshi; Misawa, Koichi; Haramizu, Satoshi; Minegishi, Yoshihiko; Hase, Tadashi

    2010-08-01

    AMP-activated protein kinase (AMPK) is a serine/threonine kinase that is implicated in the control of energy metabolism and is considered to be a molecular target for the suppression of obesity and the treatment of metabolic syndrome. Here, we identified and characterized nootkatone, a constituent of grapefruit, as a naturally occurring AMPK activator. Nootkatone induced an increase in AMPKalpha1 and -alpha2 activity along with an increase in the AMP/ATP ratio and an increase the phosphorylation of AMPKalpha and the downstream target acetyl-CoA carboxylase (ACC), in C(2)C(12) cells. Nootkatone-induced activation of AMPK was possibly mediated both by LKB1 and Ca(2+)/calmodulin-dependent protein kinase kinase. Nootkatone also upregulated PPARgamma coactivator-1alpha in C(2)C(12) cells and C57BL/6J mouse muscle. In addition, administration of nootkatone (200 mg/kg body wt) significantly enhanced AMPK activity, accompanied by LKB1, AMPK, and ACC phosphorylation in the liver and muscle of mice. Whole body energy expenditure evaluated by indirect calorimetry was also increased by nootkatone administration. Long-term intake of diets containing 0.1% to 0.3% (wt/wt) nootkatone significantly reduced high-fat and high-sucrose diet-induced body weight gain, abdominal fat accumulation, and the development of hyperglycemia, hyperinsulinemia, and hyperleptinemia in C57BL/6J mice. Furthermore, endurance capacity, evaluated as swimming time to exhaustion in BALB/c mice, was 21% longer in mice fed 0.2% nootkatone than in control mice. These findings indicate that long-term intake of nootkatone is beneficial toward preventing obesity and improving physical performance and that these effects are due, at least in part, to enhanced energy metabolism through AMPK activation in skeletal muscle and liver. PMID:20501876

  5. Effects of macronutrient composition and cyclooxygenase-inhibition on diet-induced obesity, low grade inflammation and glucose homeostasis

    DEFF Research Database (Denmark)

    Fjære, Even

    Background: Obesity and its related metabolic complications are an increasing problem worldwide. A high fat diet in combination with sucrose has been shown to induce obesity and development of glucose intolerance and insulin resistance in rodents. C57BL/6J mice were fed high fat diets with sucrose......- or protein based background, and supplemented with either corn- or fish oil. These experiments were conducted to determine whether macronutrient composition and type of dietary fat can modulate diet-induced obesity, and associated metabolic consequences. The use of non-steroidal anti....../high diet in combination with indomethacin, a nonselective cyclooxygenase cyclooxygenase-inhibitor, reduces energy efficiency and fat mass in C57BL/6J mice. Despite prevention of obesity development, indomethacin treatment was associated with hyperglycemia and reduced glucose tolerance. Body weight was not...

  6. 饮食诱导肥胖与肥胖抵抗大鼠ATP生成量的比较%The comparison of ATP contents between diet-induced obesity group and diet-induced obesity resistance group

    Institute of Scientific and Technical Information of China (English)

    王双; 胡丽贞; 于海涛; 梁冰; 薛宏凤; 李雅杰; 王舒然

    2013-01-01

    目的 比较饮食诱导肥胖大鼠与肥胖抵抗大鼠三磷酸腺苷(adenosine triphosphate,ATP)生成量的差异.方法 将健康雄性远交群(sprague dawley,SD)大鼠,随机分为基础饲料(control,CON)组和高脂饲料组,喂养2周后,将高脂饲料组按照体重增加量分为饮食诱导肥胖(diet-induced obesity,DIO)组和饮食诱导抵抗(diet-induced obesity resistance,DR)组.于喂养第10周末,麻醉处死动物,观察体重、摄食量、能量利用率以及肝脏、心脏、肌肉组织中ATP生成量的情况.结果 DIO组的体重一直高于DR组(均有P<0.05).DIO组总能量摄入高于DR组和CON组(均有P<0.001),但DIO组与DR组能量利用率差异无统计学意义.DR组大鼠肝脏、心脏和肌肉组织中ATP生成量比DIO组分别高出12.8%,30.6%和11.6%.结论 饮食诱导肥胖和肥胖抵抗大鼠的能量代谢存在差异,这种差异可能与主要能量器官中ATP的生成量有关.%Objective To compare the ATP contents in tissues between diet-induced obesity(DIO) group and diet-induced obesity resistance (DR) group. Methods Forty-eight male sprague dawley (SD) rats were randomly divided into control group and high-fat group which were given different diets. After 2-week feeding, the high-fat group were divided into diet-induced obesity group and diet-induced obesity resistance group. The rats were sacrificed for tissues and blood sample at the end of week 10. Results The body weight of DIO group was higher than that of DR group during the feeding (all P < 0. 05 ) . The total energy intake of DIO group was higher than that of DR group and CON group ( all P < 0. 001). No significance were observed of energy utilization between DIO group and DR group. The ATP contents of DIO group were 12. 8% , 30. 6% , and 11. 6% lower than that of DR group in liver, cardiac and muscle separately. Conclusions The differences of energy utilization between DIO group and DR group may be related with the ATP contents in

  7. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    International Nuclear Information System (INIS)

    Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C15 and Ob15) and 30 (C30 and Ob30) consecutive weeks. Obesity was determined by adiposity index. The Ob15 group was similar to the C15 group regarding the expression of myocardial collagen type I; however, expression in the Ob30 group was less than C30 group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob30 when compared with Ob15. Obesity did not affect collagen type III expression. This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression

  8. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Danielle Cristina Tomaz da [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Lima-Leopoldo, Ana Paula; Leopoldo, André Soares [Departamento de Esportes, Centro de Educação Física e Desportos da Universidade Federal do Espírito Santo (UFES), Vitória, ES (Brazil); Campos, Dijon Henrique Salomé de; Nascimento, André Ferreira do [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Oliveira, Sílvio Assis Junior de [Escola de Fisioterapia da Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil); Padovani, Carlos Roberto [Departamento de Bioestatística do Instituto de Ciências Biológicas da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Cicogna, Antonio Carlos, E-mail: dany.tomaz@gmail.com [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil)

    2014-02-15

    Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C{sub 15} and Ob{sub 15}) and 30 (C{sub 30} and Ob{sub 30}) consecutive weeks. Obesity was determined by adiposity index. The Ob{sub 15} group was similar to the C{sub 15} group regarding the expression of myocardial collagen type I; however, expression in the Ob{sub 30} group was less than C{sub 30} group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob{sub 30} when compared with Ob{sub 15}. Obesity did not affect collagen type III expression. This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression.

  9. A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents.

    Directory of Open Access Journals (Sweden)

    Louise S Dalbøge

    Full Text Available Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO and hypercholesterolemia Golden Syrian hamster model.Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days, normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4 inhibitor, linagliptin (3.0 mg/kg, PO, QD also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day or neuromedin U (NMU, 1.5 mg/kg/day, continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents.

  10. Myostatin expression, lymphocyte population, and potential cytokine production correlate with predisposition to high-fat diet induced obesity in mice.

    Directory of Open Access Journals (Sweden)

    Jeri-Anne Lyons

    Full Text Available A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO resistant (SWR/J and susceptible (C57BL/6 mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4(+/CD44(hi and CD8(+/CD44(hi cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism.

  11. Effect of Ethanolic Extract of Fragaria Vesca on serum glucose levels and body weight in diet induced obese rats

    OpenAIRE

    Venkat ramana Yella; Asha P Dass

    2015-01-01

    Objective: to evaluate the effect of ethanolic extract Fragaria Vesca on serum glucose levels in diet induced obese rats.Material and methods: Male Wister albino rats weighing 200- 250 gm, were divided into 3 groups of 6 animals each. The animals of all the groups except normal group were given a lipid diet consisting of cholesterol (1%), cholic acid (0.5%), casein (20%), choline (0.25%), d-l-methionin1(0.4%), coconut oil (25%), multi vitamin mix (3.5%) and sucrose (48.4%) with standard pelle...

  12. Antiobesity and Hypolipidemic Activity of Moringa oleifera Leaves against High Fat Diet-Induced Obesity in Rats

    OpenAIRE

    Souravh Bais; Guru Sewak Singh; Ramica Sharma

    2014-01-01

    In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/d...

  13. Post-transcriptional Stabilization of Ucp1 mRNA Protects Mice from Diet-Induced Obesity

    OpenAIRE

    Akinori Takahashi; Shungo Adachi; Masahiro Morita; Miho Tokumasu; Tohru Natsume; Toru Suzuki; Tadashi Yamamoto

    2015-01-01

    Uncoupling protein 1 (Ucp1) contributes to thermogenesis, and its expression is regulated at the transcriptional level. Here, we show that Ucp1 expression is also regulated post-transcriptionally. In inguinal white adipose tissue (iWAT) of mice fed a high-fat diet (HFD), Ucp1 level decreases concomitantly with increases in Cnot7 and its interacting partner Tob. HFD-fed mice lacking Cnot7 and Tob express elevated levels of Ucp1 mRNA in iWAT and are resistant to diet-induced obesity. Ucp1 mRNA ...

  14. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Steven D Kunkel

    Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  15. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice

    NARCIS (Netherlands)

    van der Heijden, Roel A.; Sheedfar, Fareeba; Morrison, Martine C.; Hommelberg, Pascal P. H.; Kor, Danny; Kloosterhuis, Niels J.; Gruben, Nanda; Youssef, Sameh A.; de Bruin, Alain; Hofker, Marten H.; Kleemann, Robert; Koonen, Debby P. Y.; Heeringa, Peter

    2015-01-01

    Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the developm

  16. Anti-obesity effect of extract from fermented Curcuma longa L. through regulation of adipogenesis and lipolysis pathway in high-fat diet-induced obese rats

    OpenAIRE

    Kim, Ji Hye; Kim, Ok-Kyung; Yoon, Ho-Geun; Park, Jeongjin; You, Yanghee; Kim, Kyungmi; Lee, Yoo-Hyun; Choi, Kyung-Chul; Lee, Jeongmin; Jun, Woojin

    2016-01-01

    Background: Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food.Objective: The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis.Design: Rats were divided into four groups (n=6 per group) after 1 week of acclimatizati...

  17. Antiobesity Effects of the Ethanol Extract of Laminaria japonica Areshoung in High-Fat-Diet-Induced Obese Rat

    Directory of Open Access Journals (Sweden)

    Woong Sun Jang

    2013-01-01

    Full Text Available Laminaria japonica Areshoung, a widely consumed marine vegetable, has traditionally been used in Korean maternal health. The present study investigated the antiobesity effects of Laminaria japonica Areshoung ethanol extract (LE and its molecular mechanism in high-fat-diet-induced obese rats. Six-week-old Sprague-Dawley male rats were separately fed a normal diet or a high-calorie high-fat diet for 6 weeks; then they were treated with LE or tea catechin for another 6 weeks. LE administration significantly decreased the body weight gain, fat-pad weights, and serum and hepatic lipid levels in HD-induced obese rats. The histological analysis revealed that LE-treated group showed a significantly decreased number of lipid droplets and size of adipocytes compared to the HD group. To elucidate the mechanism of action of LE, the levels of genes and proteins involved in obesity were measured in the liver and skeletal muscle. LE treatment resulted in an increased expression of fatty acid oxidation and thermogenesis-related genes in obese rats. Conversely, the expression of the fat intake-related gene (ACC2 and lipogenesis-related genes was reduced by LE treatment. Additionally, LE treatment increased the phosphorylation of AMP-activated protein kinase and its direct downstream protein, acetyl coenzyme A carboxylase, which is one of the rate-limiting enzymes in fatty acid synthesis pathway. These findings demonstrate that LE treatment has a protective effect against a high-fat-diet-induced obesity in rats through regulation of expression of genes and proteins involved in lipolysis and lipogenesis.

  18. Circadian Disruption and Diet-Induced Obesity Synergize to Promote Development of β-Cell Failure and Diabetes in Male Rats.

    Science.gov (United States)

    Qian, Jingyi; Yeh, Bonnie; Rakshit, Kuntol; Colwell, Christopher S; Matveyenko, Aleksey V

    2015-12-01

    There are clear epidemiological associations between circadian disruption, obesity, and pathogenesis of type 2 diabetes. The mechanisms driving these associations are unclear. In the current study, we hypothesized that continuous exposure to constant light (LL) compromises pancreatic β-cell functional and morphological adaption to diet-induced obesity leading to development of type 2 diabetes. To address this hypothesis, we studied wild type Sprague Dawley as well as Period-1 luciferase reporter transgenic rats (Per1-Luc) for 10 weeks under standard light-dark cycle (LD) or LL with concomitant ad libitum access to either standard chow or 60% high-fat diet (HFD). Exposure to HFD led to a comparable increase in food intake, body weight, and adiposity in both LD- and LL-treated rats. However, LL rats displayed profound loss of behavioral circadian rhythms as well as disrupted pancreatic islet clock function characterized by the impairment in the amplitude and the phase islet clock oscillations. Under LD cycle, HFD did not adversely alter diurnal glycemia, diurnal insulinemia, β-cell secretory function as well as β-cell survival, indicating successful adaptation to increased metabolic demand. In contrast, concomitant exposure to LL and HFD resulted in development of hyperglycemia characterized by loss of diurnal changes in insulin secretion, compromised β-cell function, and induction of β-cell apoptosis. This study suggests that circadian disruption and diet-induced obesity synergize to promote development of β-cell failure, likely mediated as a consequence of impaired islet clock function. PMID:26348474

  19. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice.

    Science.gov (United States)

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-06-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment. PMID:27419109

  20. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    Science.gov (United States)

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism. PMID:26914024

  1. White Pitaya (Hylocereus undatus Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    Haizhao Song

    Full Text Available Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2 but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos. In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism.

  2. Beyond the Role of Dietary Protein and Amino Acids in the Prevention of Diet-Induced Obesity

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    Klaus J. Petzke

    2014-01-01

    Full Text Available High-protein diets have been shown to prevent the development of diet-induced obesity and can improve associated metabolic disorders in mice. Dietary leucine supplementation can partially mimic this effect. However, the molecular mechanisms triggering these preventive effects remain to be satisfactorily explained. Here we review studies showing a connection between high protein or total amino nitrogen intake and obligatory water intake. High amino nitrogen intake may possibly lower lipid storage, and prevent insulin resistance. Suggestions are made for further systematical studies to explore the relationship between water consumption, satiety, and energy expenditure. Moreover, these examinations should better distinguish between leucine-specific and unspecific effects. Research in this field can provide important information to justify dietary recommendations and strategies in promoting long-term weight loss and may help to reduce health problems associated with the comorbidities of obesity.

  3. A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats

    DEFF Research Database (Denmark)

    Henriksen, Kim; Byrjalsen, Inger; Nielsen, Rasmus H;

    2009-01-01

    Agonists of Perioxisome Proliferator-Activator Receptor gamma (PPARgamma), which work as insulin sensitizers, are approved for type 2 diabetes. However, adverse effects, such as oedemas, infarctions, and increased fracture rates, limit their applicability. We performed a head-to-head comparison of...... equipotent glucose lowering concentrations of the partial PPARgamma agonist balaglitazone and the full agonist pioglitazone in male diet-induced obese rats, to investigate effects on bone formation, fluid retention and fat accumulation. Sixty male dio induced obese rats were divided into five categories...... oral glucose tolerance test was performed to evaluate glucose homeostasis in the rats. During oral glucose tolerance test both pioglitazone and balaglitazone lowered baseline glucose and maintained the suppression during the oral glucose tolerance test. Both lowered basal insulin, peak insulin...

  4. Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats

    Science.gov (United States)

    Aguila, Jay; McConell, Glenn K.; McAinch, Andrew J.; Mathai, Michael L.

    2016-01-01

    Background and Aims Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks. Animals received 50mg/kg body weight and 8% of total energy intake per day of TCTs and/or WPIs respectively. Food intake, body composition, glucose tolerance, insulin sensitivity, exercise capacity, skeletal muscle glycogen content and oxidative enzyme activity were determined. Results Both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (P<0.05), TCT + WPI did not further improve exercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (P<0.05 vs. Control) but not in the plantaris. Citrate synthase activity was not different between groups. Neither supplement had any effect on weight gain, adiposity, glucose tolerance or insulin sensitivity. Conclusion Ten weeks of both TCTs and WPIs increased exercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance. PMID:27058737

  5. High-fat-diet-induced obesity causes an inflammatory and tumor-promoting microenvironment in the rat kidney

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    Kerstin Stemmer

    2012-09-01

    Obesity and concomitant comorbidities have emerged as public health problems of the first order. For instance, obese individuals have an increased risk for kidney cancer. However, direct mechanisms linking obesity with kidney cancer remain elusive. We hypothesized that diet-induced obesity (DIO promotes renal carcinogenesis by inducing an inflammatory and tumor-promoting microenvironment. We compared chow-fed lean Wistar rats with those that were sensitive (DIOsens or partially resistant (DIOres to DIO to investigate the impact of body adiposity versus dietary nutrient overload in the development of renal preneoplasia and activation of tumor-promoting signaling pathways. Our data clearly show a correlation between body adiposity, the severity of nephropathy, and the total number and incidence of preneoplastic renal lesions. However, similar plasma triglyceride, plasma free fatty acid and renal triglyceride levels were found in chow-fed, DIOres and DIOsens rats, suggesting that lipotoxicity is not a critical contributor to the renal pathology. Obesity-related nephropathy was further associated with regenerative cell proliferation, monocyte infiltration and higher renal expression of monocyte chemotactic protein-1 (MCP-1, interleukin (IL-6, IL-6 receptor and leptin receptor. Accordingly, we observed increased signal transducer and activator of transcription 3 (STAT3 and mammalian target of rapamycin (mTOR phosphorylation in tubules with preneoplastic phenotypes. In summary, our results demonstrate that high body adiposity induces an inflammatory and proliferative microenvironment in rat kidneys that promotes the development of preneoplastic lesions, potentially via activation of the STAT3 and mTOR signaling pathways.

  6. Protective effect of gymnema sylvestre ethanol extract on high fat diet-induced obese diabetic wistar rats

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    V Kumar

    2014-01-01

    Full Text Available Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate, serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose, cardiomyocyte apoptosis (cardiac caspase-3, Na + /K + ATPase activity and DNA fragmentation organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o. for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na + /K + ATPase activity and DNA laddering, visceral fat pad and organ′s weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus.

  7. Effect of Lactobacillus plantarum FH185 on the Reduction of Adipocyte Size and Gut Microbial Changes in Mice with Diet-induced Obesity

    OpenAIRE

    Park, Sun-Young; Cho, Seong-A; Lee, Myung-Ki; Lim, Sang-Dong

    2015-01-01

    This study aimed to investigate the effects of Lactobacillus plantarum FH185 on the reduction of adipocyte size and gut microbial changes in mice with diet-induced obesity. The strain was found to have a lipase inhibitory activity of 70.09±2.04% and inhibited adipocyte differentiation of 3T3-L1 cells (18.63±0.98%) at a concentration of 100 µg/mL. To examine the effect of the strain supplementation on gut microbial changes in mice with diet-induced obesity, male C57BL/6J mice were fed on four ...

  8. Subcutaneous Adipose Tissue Transplantation in Diet-Induced Obese Mice Attenuates Metabolic Dysregulation While Removal Exacerbates It.

    Science.gov (United States)

    Foster, M T; Softic, S; Caldwell, J; Kohli, R; de Kloet, A D; Seeley, R J

    2013-08-01

    Adipose tissue distribution is an important determinant of obesity-related comorbidities. It is well established that central obesity (visceral adipose tissue accumulation) is a risk factor for many adverse health consequences such as dyslipidemia, insulin resistance and type-2-diabetes. We hypothesize that the metabolic dysregulation that occurs following high fat diet-induced increases in adiposity are due to alterations in visceral adipose tissue function which influence lipid flux to the liver via the portal vein. This metabolic pathology is not exclusively due to increases in visceral adipose tissue mass but also driven by intrinsic characteristics of this particular depot. In Experiment 1, high fat diet (HFD)-induced obese control (abdominal incision, but no fat manipulation) or autologous (excision and subsequent relocation of adipose tissue) subcutaneous tissue transplantation to the visceral cavity. In Experiment 2 mice received control surgery, subcutaneous fat removal or hetero-transplantation (tissue from obese donor) to the visceral cavity. Body composition analysis and glucose tolerance tests were performed 4 weeks post-surgery. Adipose mass and portal adipokines, cytokines, lipids and insulin were measured from samples collected at 5 weeks post-surgery. Auto- and hetero- transplantation in obese mice improved glucose tolerance, decreased systemic insulin concentration and reduced portal lipids and hepatic triglycerides compared with HFD controls. Hetero-transplantation of subcutaneous adipose tissue to the visceral cavity in obese mice restored hepatic insulin sensitivity and reduced insulin and leptin concentrations to chow control levels. Fat removal, however, as an independent procedure exacerbated obesity-induced increases in leptin and insulin concentrations. Overall subcutaneous adipose tissue protects against aspects of metabolic dysregulation in obese mice. Transplantation-induced improvements do not occur via enhanced storage of lipid in

  9. The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a mouse model of diet induced obesity.

    Science.gov (United States)

    Rodríguez-Rodríguez, César; Torres, Nimbe; Gutiérrez-Uribe, Janet A; Noriega, Lilia G; Torre-Villalvazo, Iván; Leal-Díaz, Ana M; Antunes-Ricardo, Marilena; Márquez-Mota, Claudia; Ordaz, Guillermo; Chavez-Santoscoy, Rocío A; Serna-Saldivar, Sergio O; Tovar, Armando R

    2015-03-01

    A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity. PMID:25588195

  10. Calorie restriction and endurance exercise share potent anti-inflammatory function in adipose tissues in ameliorating diet-induced obesity and insulin resistance in mice

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    Yan Zhen

    2010-07-01

    Full Text Available Abstract Background Calorie restriction (CR and endurance exercise are known to attenuate obesity and improve the metabolic syndrome. The aim of this study was to directly compare the effects of CR and endurance exercise in a mouse model of diet-induced obesity and insulin resistance. Methods Adult male C57BL/6N mice were randomly assigned and subjected to one of the six interventions for 8 weeks: low-fat diet (LC, 10% fat, low-fat diet with 30% calorie restriction (LR, high-fat diet (HC, 60% fat, high-fat diet with 30% calorie restriction (HR, high-fat diet with voluntary running exercise (HE, and high-fat diet with a combination of 30% calorie restriction and exercise (HRE. The impacts of the interventions were assessed by comprehensive metabolic analyses and pro-inflammatory cytokine gene expression. Results Endurance exercise significantly attenuated high-fat diet-induced obesity. CR dramatically prevented high-fat diet-induced metabolic abnormalities. A combination of CR and endurance exercise further reduced obesity and insulin resistance under the condition of high-fat diet. CR and endurance exercise each potently suppressed the expression of inflammatory cytokines in white adipose tissues with additive effects when combined, but the effects of diet and exercise interventions in the liver were moderate to minimal. Conclusions CR and endurance exercise share a potent anti-inflammatory function in adipose tissues in ameliorating diet-induced obesity and insulin resistance.

  11. Apple-Derived Pectin Modulates Gut Microbiota, Improves Gut Barrier Function, and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity.

    Science.gov (United States)

    Jiang, Tingting; Gao, Xuejin; Wu, Chao; Tian, Feng; Lei, Qiucheng; Bi, Jingcheng; Xie, Bingxian; Wang, Hong Yu; Chen, Shuai; Wang, Xinying

    2016-01-01

    This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8) or a high-fat diet (HFD; n = 32) for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8) or pectin-supplemented HFD (HF-P group; n = 8) for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats. PMID:26938554

  12. Peripheral reduction of FGFR4 with antisense oligonucleotides increases metabolic rate and lowers adiposity in diet-induced obese mice.

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    Xing Xian Yu

    Full Text Available Obesity is a primary risk factor for multiple metabolic disorders. Many drugs for the treatment of obesity, which mainly act through CNS as appetite suppressants, have failed during development or been removed from the market due to unacceptable adverse effects. Thus, there are very few efficacious drugs available and remains a great unmet medical need for anti-obesity drugs that increase energy expenditure by acting on peripheral tissues without severe side effects. Here, we report a novel approach involving antisense inhibition of fibroblast growth factor receptor 4 (FGFR4 in peripheral tissues. Treatment of diet-induce obese (DIO mice with FGFR4 antisense oligonucleotides (ASO specifically reduced liver FGFR4 expression that not only resulted in decrease in body weight (BW and adiposity in free-feeding conditions, but also lowered BW and adiposity under caloric restriction. In addition, combination treatment with FGFR4 ASO and rimonabant showed additive reduction in BW and adiposity. FGFR4 ASO treatment increased basal metabolic rate during free-feeding conditions and, more importantly, prevented adaptive decreases of metabolic rate induced by caloric restriction. The treatment increased fatty acid oxidation while decreased lipogenesis in both liver and fat. Mechanistic studies indicated that anti-obesity effect of FGFR4 ASO was mediated at least in part through an induction of plasma FGF15 level resulted from reduction of hepatic FGFR4 expression. The anti-obesity effect was accompanied by improvement in plasma glycemia, whole body insulin sensitivity, plasma lipid levels and liver steatosis. Therefore, FGFR4 could be a potential novel target and antisense reduction of hepatic FGFR4 expression could be an efficacious therapy as an adjunct to diet restriction or to an appetite suppressant for the treatment of obesity and related metabolic disorders.

  13. MsrA Overexpression Targeted to the Mitochondria, but Not Cytosol, Preserves Insulin Sensitivity in Diet-Induced Obese Mice.

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    JennaLynn Hunnicut

    Full Text Available There is growing evidence that oxidative stress plays an integral role in the processes by which obesity causes type 2 diabetes. We previously identified that mice lacking the protein oxidation repair enzyme methionine sulfoxide reductase A (MsrA are particularly prone to obesity-induced insulin resistance suggesting an unrecognized role for this protein in metabolic regulation. The goals of this study were to test whether increasing the expression of MsrA in mice can protect against obesity-induced metabolic dysfunction and to elucidate the potential underlying mechanisms. Mice with increased levels of MsrA in the mitochondria (TgMito MsrA or in the cytosol (TgCyto MsrA were fed a high fat/high sugar diet and parameters of glucose homeostasis were monitored. Mitochondrial content, markers of mitochondrial proteostasis and mitochondrial energy utilization were assessed. TgMito MsrA, but not TgCyto MsrA, mice remain insulin sensitive after high fat feeding, though these mice are not protected from obesity. This metabolically healthy obese phenotype of TgMito MsrA mice is not associated with changes in mitochondrial number or biogenesis or with a reduction of proteostatic stress in the mitochondria. However, our data suggest that increased mitochondrial MsrA can alter metabolic homeostasis under diet-induced obesity by activating AMPK signaling, thereby defining a potential mechanism by which this genetic alteration can prevent insulin resistance without affecting obesity. Our data suggest that identification of targets that maintain and regulate the integrity of the mitochondrial proteome, particular against oxidative damage, may play essential roles in the protection against metabolic disease.

  14. Anti-obesity effect of extract from fermented Curcuma longa L. through regulation of adipogenesis and lipolysis pathway in high-fat diet-induced obese rats

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    Ji Hye Kim

    2016-01-01

    Full Text Available Background: Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food. Objective: The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis. Design: Rats were divided into four groups (n=6 per group after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w./day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50 with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks. Results: We found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG, and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and β-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase. Conclusions: These results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis.

  15. Prognostic markers for diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Astrup, A; Buemann, B; Gluud, C;

    1995-01-01

    To identify prognostic metabolic and hormonal markers for long-term weight loss outcome in obese women.......To identify prognostic metabolic and hormonal markers for long-term weight loss outcome in obese women....

  16. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V;

    2014-01-01

    study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ......We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present...... food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action was...

  17. Emodin improves lipid and glucose metabolism in high fat diet-induced obese mice through regulating SREBP pathway.

    Science.gov (United States)

    Li, Jinmei; Ding, Lili; Song, Baoliang; Xiao, Xu; Qi, Meng; Yang, Qiaoling; Yang, Qiming; Tang, Xiaowen; Wang, Zhengtao; Yang, Li

    2016-01-01

    Currently, obesity has become a worldwide epidemic associated with Type 2 diabetes, dyslipidemia, cardiovascular disease and chronic metabolic diseases. Emodin is one of the active anthraquinone derivatives from Rheum palmatum and some other Chinese herbs with anti-inflammatory, anticancer and hepatoprotective properties. In the present study, we investigated the anti-obesity effects of emodin in obese mice and explore its potential pharmacological mechanisms. Male C57BL/6 mice were fed with high-fat diet for 12 weeks to induce obesity. Then the obese mice were divided into four groups randomly, HFD or emodin (40mg/kg/day and 80mg/kg/day) or lovastatin (30mg/kg/ day) for another 6 weeks. Body weight and food intake were recorded every week. At the end of the treatment, the fasting blood glucose, glucose and insulin tolerance test, serum and hepatic lipid levels were assayed. The gene expressions of liver and adipose tissues were analyzed with a quantitative PCR assay. Here, we found that emodin inhibited sterol regulatory element-binding proteins (SREBPs) transactivity in huh7 cell line. Furthermore, emodin (80mg/kg/day) treatment blocked body weight gain, decreased blood lipids, hepatic cholesterol and triglyceride content, ameliorated insulin sensitivity, and reduced the size of white and brown adipocytes. Consistently, SREBP-1 and SREBP-2 mRNA levels were significantly reduced in the liver and adipose tissue after emodin treatment. These data demonstrated that emodin could improve high-fat diet-induced obesity and associated metabolic disturbances. The underlying mechanism is probably associated with regulating SREBP pathway. PMID:26626587

  18. Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse.

    Science.gov (United States)

    Daly, Donna M; Park, Sung Jin; Valinsky, William C; Beyak, Michael J

    2011-06-01

    Gastrointestinal vagal afferents transmit satiety signals to the brain via both chemical and mechanical mechanisms. There is indirect evidence that these signals may be attenuated in obesity. We hypothesized that responses to satiety mediators and distension of the gut would be attenuated after induction of diet induced obesity. Obesity was induced by feeding a high fat diet (60% kcal from fat). Low fat fed mice (10% kcal from fat) served as a control. High fat fed mice were obese, with increased visceral fat, but were not hyperglycaemic. Recordings from jejunal afferents demonstrated attenuated responses to the satiety mediators cholecystokinin (CCK, 100 nm) and 5-hydroxytryptamine (5-HT, 10 μm), as was the response to low intensity jejunal distension, while responses to higher distension pressures were preserved. We performed whole cell patch clamp recordings on nodose ganglion neurons, both unlabelled, and those labelled by fast blue injection into the wall of the jejunum. The cell membrane of both labelled and unlabelled nodose ganglion neurons was less excitable in HFF mice, with an elevated rheobase and decreased number of action potentials at twice rheobase. Input resistance of HFF neurons was also significantly decreased. Calcium imaging experiments revealed reduced proportion of nodose ganglion neurons responding to CCK and 5-HT in obese mice. These results demonstrate a marked reduction in afferent sensitivity to satiety related stimuli after a chronic high fat diet. A major mechanism underlying this change is reduced excitability of the neuronal cell membrane. This may explain the development of hyperphagia when a high fat diet is consumed. Improving sensitivity of gastrointestinal afferent nerves may prove useful to limit food intake in obesity. PMID:21486762

  19. Adipocyte-Specific Deletion of Manganese Superoxide Dismutase Protects From Diet-Induced Obesity Through Increased Mitochondrial Uncoupling and Biogenesis.

    Science.gov (United States)

    Han, Yong Hwan; Buffolo, Márcio; Pires, Karla Maria; Pei, Shaobo; Scherer, Philipp E; Boudina, Sihem

    2016-09-01

    Obesity and insulin resistance are associated with oxidative stress (OS). The causal role of adipose OS in the pathogenesis of these conditions is unknown. To address this issue, we generated mice with an adipocyte-selective deletion of manganese superoxide dismutase (MnSOD). When fed a high-fat diet (HFD), the AdSod2 knockout (KO) mice exhibited less adiposity, reduced adipocyte hypertrophy, and decreased circulating leptin. The resistance to diet-induced adiposity was the result of an increased metabolic rate and energy expenditure. Furthermore, palmitate oxidation was elevated in the white adipose tissue (WAT) and brown adipose tissue of AdSod2 KO mice fed an HFD, and the expression of key fatty acid oxidation genes was increased. To gain mechanistic insight into the increased fat oxidation in HFD-fed AdSod2 KO mice, we quantified the mitochondrial function and mitochondrial content in WAT and found that MnSOD deletion increased mitochondrial oxygen consumption and induced mitochondrial biogenesis. This effect was preserved in cultured adipocytes from AdSod2 KO mice in vitro. As expected from the enhanced fat oxidation, circulating levels of free fatty acids were reduced in the HFD-fed AdSod2 KO mice. Finally, HFD-fed AdSod2 KO mice were protected from hepatic steatosis, adipose tissue inflammation, and glucose and insulin intolerance. Taken together, these results demonstrate that MnSOD deletion in adipocytes triggered an adaptive stress response that activated mitochondrial biogenesis and enhanced mitochondrial fatty acid oxidation, thereby preventing diet-induced obesity and insulin resistance. PMID:27284109

  20. PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

    DEFF Research Database (Denmark)

    Vrang, Niels; Madsen, Andreas Nygaard; Tang-Christensen, Mads;

    2006-01-01

    The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single intraperit...... conditioned taste aversion in male rats....

  1. Adrenalectomy stimulates hypothalamic proopiomelanocortin expression but does not correct diet-induced obesity

    OpenAIRE

    Beasley Joe; Mizuno Tooru M; Makimura Hideo; Silverstein Jeffrey H; Mobbs Charles V

    2003-01-01

    Abstract Background Elevated glucocorticoid production and reduced hypothalamic POMC mRNA can cause obese phenotypes. Conversely, adrenalectomy can reverse obese phenotypes caused by the absence of leptin, a model in which glucocorticoid production is elevated. Adrenalectomy also increases hypothalamic POMC mRNA in leptin-deficient mice. However most forms of human obesity do not appear to entail elevated plasma glucocorticoids. It is therefore not clear if reducing glucocorticoid production ...

  2. CORRELATIONS BETWEEN BLOOD PRESSURE AND BODY WEIGHT, SERUM LEPTIN IN HIGH CALORIE DIET-INDUCED OBESE RATS

    Institute of Scientific and Technical Information of China (English)

    Hu Zhi; Ma Aiqun; Yang Chun; Tian Hongyan

    2006-01-01

    Objective To examine the change of body weight (BW) and blood pressure (BP) in obese rats, clarify relationships between BP and BW and other factors. Methods Male Spraque-Dawley rats were fed either with normal diet (ND) or high calorie diet (HC) for 20 weeks. BW and BP of tail artery were observed biweekly and tetraweekly respectively; serum leptin and fasting insulin (FINS) were detected by enzyme-linked immunoadsordent assay (ELISA) and radioimmunoassay (RIA) respectively. Fasting plasma glucose (FPG) and free fatty acid(FFA) were measured by conventional means. Results BW, abdominal fat weight (AFW), ratio of abdominal fat weight to body weight (RF/W), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum levels of leptin and FINS, FPG, FFA increased in the HD group after 20 weeks diet intervention (P<0.05 or P<0.01). SBP was strongly correlated with BW, leptin, FINS and FFA (P<0.05), DBP was correlated with FFA (r=0.47, P<0.05). In addition, leptin was positively correlated with BW, AFW, RF/W, FINS and FFA (P<0.05 or P<0.01). Conclusion In this study of high calorie-diet induced rats, the gain of BW is accompanied by increased BP. The obese rats have hyperleptinemia, hyperinsulinemia, hyperglycemia and dyslipidemia which may have important effects on the development of obesity-related hypertension. RF/W is the key factor in which affect serum leptin level.

  3. AT1 receptor blockade attenuates insulin resistance and myocardial remodeling in rats with diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Silvio A Oliveira-Junior

    Full Text Available BACKGROUND: Although obesity has been associated with metabolic and cardiac disturbances, the carrier mechanisms for these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet-induced obesity. MATERIAL AND METHODS: Wistar-Kyoto (n = 40 rats were subjected to control (C; 3.2 kcal/g and hypercaloric diets (OB; 4.6 kcal/g for 30 weeks. Subsequently, rats were distributed to four groups: C, CL, OB, and OBL. L groups received Losartan (30 mg/kg/day for five weeks. After this period we performed in vivo glucose tolerance and insulin tolerance tests, and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE, and leptin levels. Cardiovascular analyzes included systolic blood pressure (SBP, echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2, c-Jun amino-terminal kinases (JNK, insulin receptor subunit β (βIR, and phosphatidylinositol 3-kinase (PI3K by Western Blot. RESULTS: Glucose metabolism, insulin, lipid, and ACE activity disorders observed with obesity were minimized by Losartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level, OB exhibited higher ERK, Tyr-phosphorylated βIR, and PI3K expression, and reduced myocardial angiotensin and JNK expression. ERK and JNK expression were regulated in the presence of Losartan, while angiotensin, Tyr-βRI, total and Tyr-phosphorylated PI3K expression were elevated in the OBL group. CONCLUSION: Angiotensin II blockade with Losartan attenuates obesity-induced metabolic and cardiovascular changes.

  4. Antiobesity effects of yerba maté extract (Ilex paraguariensis) in high-fat diet-induced obese mice.

    Science.gov (United States)

    Arçari, Demétrius P; Bartchewsky, Waldemar; dos Santos, Tanila W; Oliveira, Karim A; Funck, Alexandre; Pedrazzoli, José; de Souza, Marina F F; Saad, Mario J; Bastos, Deborah H M; Gambero, Alessandra; Carvalho, Patricia de O; Ribeiro, Marcelo L

    2009-12-01

    Because the potential of yerba maté (Ilex paraguariensis) has been suggested in the management of obesity, the aim of the present study was to evaluate the effects of yerba maté extract on weight loss, obesity-related biochemical parameters, and the regulation of adipose tissue gene expression in high-fat diet-induced obesity in mice. Thirty animals were randomly assigned to three groups. The mice were introduced to standard or high-fat diets. After 12 weeks on a high-fat diet, mice were randomly assigned according to the treatment (water or yerba maté extract 1.0 g/kg). After treatment intervention, plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and glucose were evaluated. Adipose tissue was examined to determine the mRNA levels of several genes such as tumor necrosis factor-alpha (TNF-alpha), leptin, interleukin-6 (IL-6), C-C motif chemokine ligand-2 (CCL2), CCL receptor-2 (CCR2), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin, peroxisome proliferator-activated receptor-gamma(2) (PPAR-gamma(2)), uncoupling protein-1 (UCP1), and PPAR-gamma coactivator-1 alpha (PGC-1 alpha). The F4/80 levels were determined by immunoblotting. We found that obese mice treated with yerba maté exhibited marked attenuation of weight gain, adiposity, a decrease in epididymal fat-pad weight, and restoration of the serum levels of cholesterol, triglycerides, LDL cholesterol, and glucose. The gene and protein expression levels were directly regulated by the high-fat diet. After treatment with yerba maté extract, we observed a recovery of the expression levels. In conclusion, our data show that yerba maté extract has potent antiobesity activity in vivo. Additionally, we observed that the treatment had a modulatory effect on the expression of several genes related to obesity. PMID:19444227

  5. Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

    Energy Technology Data Exchange (ETDEWEB)

    Banin, R.M.; Hirata, B.K.S. [Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP (Brazil); Andrade, I.S.; Zemdegs, J.C.S. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Clemente, A.P.G. [Faculdade de Nutrição, Universidade Federal de Alagoas, Maceió, AL (Brazil); Dornellas, A.P.S.; Boldarine, V.T. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Estadella, D. [Departamento de Biociências, Universidade Federal de São Paulo, Baixada Santista, SP (Brazil); Albuquerque, K.T. [Curso de Nutrição, Universidade Federal do Rio de Janeiro, Macaé, RJ (Brazil); Oyama, L.M.; Ribeiro, E.B. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Telles, M.M. [Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP (Brazil)

    2014-07-25

    Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

  6. Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

    Directory of Open Access Journals (Sweden)

    R.M. Banin

    2014-09-01

    Full Text Available Ginkgo biloba extract (GbE has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1, protein tyrosine phosphatase 1B (PTP-1B, and protein kinase B (Akt, as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD or a normal fat diet (NFD for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V, and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb. NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

  7. Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

    International Nuclear Information System (INIS)

    Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment

  8. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice

    OpenAIRE

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-01-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippo...

  9. Diet-induced and mono-genetic obesity alter volatile organic compound signature in mice.

    Science.gov (United States)

    Kistler, Martin; Muntean, Andreea; Szymczak, Wilfried; Rink, Nadine; Fuchs, Helmut; Gailus-Durner, Valerie; Wurst, Wolfgang; Hoeschen, Christoph; Klingenspor, Martin; Hrabě de Angelis, Martin; Rozman, Jan

    2016-03-01

    The prevalence of obesity is still rising in many countries, resulting in an increased risk of associated metabolic diseases. In this study we aimed to describe the volatile organic compound (VOC) patterns symptomatic for obesity. We analyzed high fat diet (HFD) induced obese and mono-genetic obese mice (global knock-in mutation in melanocortin-4 receptor MC4R-ki). The source strengths of 208 VOCs were analyzed in ad libitum fed mice and after overnight food restriction. Volatiles relevant for a random forest-based separation of obese mice were detected (26 in MC4R-ki, 22 in HFD mice). Eight volatiles were found to be important in both obesity models. Interestingly, by creating a partial correlation network of the volatile metabolites, the chemical and metabolic origins of several volatiles were identified. HFD-induced obese mice showed an elevation in the ketone body acetone and acrolein, a marker of lipid peroxidation, and several unidentified volatiles. In MC4R-ki mice, several yet-unidentified VOCs were found to be altered. Remarkably, the pheromone (methylthio)methanethiol was found to be reduced, linking metabolic dysfunction and reproduction. The signature of volatile metabolites can be instrumental in identifying and monitoring metabolic disease states, as shown in the screening of the two obese mouse models in this study. Our findings show the potential of breath gas analysis to non-invasively assess metabolic alterations for personalized diagnosis. PMID:26860833

  10. Analysis of gene expression in pancreatic islets from diet-induced obese mice

    OpenAIRE

    Imai, Yumi; Patel, Hiral R.; Nicolai M. Doliba; Matschinsky, Franz M.; Tobias, John W.; Ahima, Rexford S.

    2008-01-01

    In insulin-resistant status such as obesity, failure of pancreatic islets to increase insulin secretion leads to diabetes. We sought to screen for the islet genes that facilitate islet adaptation to obesity by comparing gene expression profiles between two strains of obesity-prone inbred mice with different propensities for hyperglycemia. C57BL/6J and AKR/J were fed regular rodent chow or high-fat diet, after which islet morphology, secretory function, and gene expression were assessed. AKR/J...

  11. Dietary Protein in the Prevention of Diet-Induced Obesity and Co-Morbidities

    DEFF Research Database (Denmark)

    Tastesen, Hanne Sørup

    Background: Obesity and related co‐morbidities are increasing problems worldwide and nutritional approaches to prevent and alleviate these diseases are thus of great interest. High‐protein diets have been shown to prevent and alleviate obesity and co‐morbidities in rodents and humans through...... increased energy expenditure and satiety. Similarly, protein from different sources and in different forms has been shown to modulate obesity and co‐morbidities. However, the impact of protein from different sources consumed at normal dietary levels remains to be further elucidated. Obesity‐prone C57BL/6J...... protein, was found to be negligible in development of obesity and co‐morbidities in mice. Seafood protein with high endogenous taurine and glycine contents was found to prevent diet‐induced adiposity and dyslipidemia, both in ad libitum and pair‐fed settings. The ability of seafood proteins to prevent...

  12. Diet Induced Obesity Causes Cerebral Vessel Remodeling and Increases the Damage Caused by Ischemic Stroke

    OpenAIRE

    Deutsch, Christian; Portik-Dobos, Vera; Smith, Anita D; Ergul, Adviye; Dorrance, Anne M.

    2009-01-01

    Hypertension, elevated fasting blood glucose and plasma insulin develop in rats fed a high fat (HF) diet. Our goal was to assess the effects of obesity, beginning in childhood, on the adult cardiovascular system. We hypothesized that rats fed a HF diet would have larger ischemic cerebral infarcts and middle cerebral artery (MCA) remodeling. Three-week-old male Sprague Dawley rats were fed a HF (Obese) or control diet for 10 weeks. Cerebral ischemia was induced by MCA occlusion (MCAO). MCA str...

  13. Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity

    OpenAIRE

    Zhu, Lin; Martinez, Melissa N.; Emfinger, Christopher H.; Palmisano, Brian T.; John M Stafford

    2014-01-01

    The development of insulin resistance in the liver is a key event that drives dyslipidemia and predicts diabetes and cardiovascular risk with obesity. Clinical data show that estrogen signaling in males helps prevent adiposity and insulin resistance, which may be mediated through estrogen receptor-α (ERα). The tissues and pathways that mediate the benefits of estrogen signaling in males with obesity are not well defined. In female mice, ERα signaling in the liver helps to correct pathway-sele...

  14. Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats

    OpenAIRE

    Mao Li; Ting Ye; Xiao-Xia Wang; Xian Li; Ou Qiang; Tao Yu; Cheng-Wei Tang; Rui Liu

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) caused by liver lipid dysregulation is linked to obesity. Somatostatin (SST) and its analogs have been used to treat pediatric hypothalamic obesity. However, the application of such drugs for the treatment of NAFLD has not been evaluated. Objective This study aimed to investigate the expression levels of important regulators of hepatic lipid metabolism and the possible effect of the SST analog octreotide on these regulators. Methods SD rats...

  15. Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model

    OpenAIRE

    Baek, Hye Kyung; Shim, Hyeji; Lim, Hyunmook; Shim, Minju; Kim, Chul-Kyu; Park, Sang-Kyu; Lee, Yong Seok; Song, Ki-Duk; Kim, Sung-Jo; Yi, Sun Shin

    2015-01-01

    Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipo...

  16. Prevention of diet-induced obesity and glucose intolerance in mice by chemical derivatives of DHA

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Jílková, Zuzana; Jeleník, Tomáš; Hensler, Michal; Mohamed-Ali, V.; Bryhn, M.

    2007-01-01

    Roč. 15, Suppl. (2007), A 185-A186. ISSN 1930-7381. [The Obesity Society 2007 Annual Scientific Meeting. 20.10.2007-24.10.2007, New Orleans] R&D Projects: GA ČR GA303/07/0708 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * obesity * high-fat diet * decosahexaenoic acid Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  17. Effects of chronic exercise on the endocannabinoid system in Wistar rats with high-fat diet-induced obesity.

    Science.gov (United States)

    Gamelin, François-Xavier; Aucouturier, Julien; Iannotti, Fabio Arturo; Piscitelli, Fabiana; Mazzarella, Enrico; Aveta, Teresa; Leriche, Melissa; Dupont, Erwan; Cieniewski-Bernard, Caroline; Montel, Valérie; Bastide, Bruno; Di Marzo, Vincenzo; Heyman, Elsa

    2016-06-01

    The endocannabinoid system is dysregulated during obesity in tissues involved in the control of food intake and energy metabolism. We examined the effect of chronic exercise on the tissue levels of endocannabinoids (eCBs) and on the expression of genes coding for cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) (Cnr1 and Cnr2, respectively) in the subcutaneous (SAT) and visceral adipose tissues and in the soleus and extensor digitorim longus (EDL) muscles, in rats fed with standard or high-fat diet. Twenty-eight male Wistar rats were placed on high-fat diet or standard diet (HFD and Ctl groups, respectively) during 12 weeks whereafter half of each group was submitted to an exercise training period of 12 weeks (HFD + training and Ctl + training). Tissue levels of eCBs were measured by LC-MS while expressions of genes coding for CB1 and CB2 receptors were investigated by qPCR. High-fat diet induced an increase in anandamide (AEA) levels in soleus and EDL (p < 0.02). In soleus of the HFD group, these changes were accompanied by elevated Cnr1 messenger RNA (mRNA) levels (p < 0.05). In EDL, exercise training allowed to reduce significantly this diet-induced AEA increase (p < 0.005). 2-Arachidonoylglycerol (2-AG) levels were decreased and increased by high-fat diet in SAT and EDL, respectively (p < 0.04), but not affected by exercise training. Unlike the HFD + training group, 2-AG levels in soleus were also decreased in the HFD group compared to Ctl (p < 0.04). The levels of eCBs and Cnr1 expression are altered in a tissue-specific manner following a high-fat diet, and chronic exercise reverses some of these alterations. PMID:26880264

  18. Female mice target deleted for the neuromedin B receptor have partial resistance to diet-induced obesity.

    Science.gov (United States)

    Paula, Gabriela Silva Monteiro; Souza, Luana Lopes; Cabanelas, Adriana; Bloise, Flavia Fonseca; Mello-Coelho, Valéria; Wada, Etsuko; Ortiga-Carvalho, Tania Maria; Oliveira, Karen Jesus; Pazos-Moura, Carmen Cabanelas

    2010-05-01

    Previous studies have proposed a role for neuromedin B (NB), a bombesin-like peptide, in the control of body weight homeostasis. However, the nature of this role is unclear. The actions of NB are mediated preferentially by NB-preferring receptors (NBRs). Here we examined the consequences of targeted deletion of NBRs in female mice on body weight homeostasis in mice fed a normolipid diet (ND) or a high-fat diet (HFD) for 13 weeks. Body weight and food ingestion of neuromedin B receptor knockout (NBR-KO) mice fed a normolipid diet showed no difference in relation to wild-type (WT). However, the high-fat diet induced an 8.9- and 4.8-fold increase in body weight of WT and NBR-KO, respectively, compared to their controls maintained with a normolipid diet, even though the mice ingested the same amount of calories, regardless of genotype. Comparing mice fed the high-fat diet, NBR-KO mice accumulated approximately 45% less fat depot mass than WT, exhibited a lower percentage of fat in their carcasses (19.2 vs. 31.3%), and their adipocytes were less hypertrophied. Serum leptin and leptin mRNA in inguinal and perigonadal fat were lower in HFD NBR-KO than HFD WT, and serum adiponectin was similar among HFD groups and unaltered in comparison to ND-fed mice. HFD-fed WT mice developed glucose intolerance but not the HFD-fed NBR-KO mice, although they had similar glycaemia and insulinaemia. NBR-KO and WT mice on the normolipid diet showed no differences in any parameters, except for a trend to lower insulin levels. Therefore, disruption of the neuromedin B receptor pathway did not change body weight homeostasis in female mice fed a normolipid diet; however, it did result in partial resistance to diet-induced obesity. PMID:20211980

  19. White adipose tissue re-growth after partial lipectomy in high fat diet induced obese wistar rats.

    Science.gov (United States)

    Bueno, Allain Amador; Habitante, Carlos Alexandre; Oyama, Lila Missae; Estadella, Débora; Ribeiro, Eliane Beraldi; Oller do Nascimento, Cláudia Maria

    2011-01-01

    The effects of partial removal of epididymal (EPI) and retroperitoneal (RET) adipose tissues (partial lipectomy) on the triacylglycerol deposition of high fat diet induced obese rats were analyzed, aiming to challenge the hypothesized body fat regulatory system. Male 28-day-old wistar rats received a diet enriched with peanuts, milk chocolate and sweet biscuits during the experimental period. At the 90th day of life, rats were submitted to either lipectomy (L) or sham surgery. After 7 or 30 days, RET, EPI, liver, brown adipose tissue (BAT), blood and carcass were obtained and analyzed. Seven days following surgery, liver lipogenesis rate and EPI relative weight were increased in L. After 30 days, L, RET and EPI presented increased lipogenesis, lipolysis and percentage of small area adipocytes. L rats also presented increased liver malic enzyme activity, BAT lipogenesis, and triacylglycerol and corticosterone serum levels. The partial removal of visceral fat pads affected the metabolism of high fat diet obese rats, which leads to excised tissue re-growth and possibly compensatory growth of non-excised depots at a later time. PMID:21140253

  20. Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tsunao Kishida

    2015-10-01

    Full Text Available Brown adipocytes (BAs play important roles in body temperature regulation, energy balance, and carbohydrate and lipid metabolism. Activities of BAs are remarkably diminished in obese and diabetic patients, providing possibilities of transplanting functional BAs resulting in therapeutic benefit. Here, we show generation of functional BAs by cellular reprogramming procedures. Transduction of the PRDM16 gene into iPSC-derived embryoid bodies induced BA phenotypes (iBAs. Moreover, normal human fibroblasts were directly converted into BAs (dBAs by C/EBP-β and C-MYC gene transduction. Approximately 90% of the fibroblasts were successfully converted within 12 days. The dBAs were highly active in mitochondrial biogenesis and oxidative metabolism. Mouse dBAs were induced by Prdm16, C/ebp-β, and L-myc genes, and after transplantation, they significantly reduced diet-induced obesity and insulin resistance in an UCP1-dependent manner. Thus, highly functional BAs can be generated by cellular reprogramming, suggesting a promising tailor-made cell therapy against metabolic disorders including type 2 diabetes mellitus.

  1. High Hydrostatic Pressure Extract of Red Ginseng Attenuates Inflammation in Rats with High-fat Diet Induced Obesity.

    Science.gov (United States)

    Jung, Sunyoon; Lee, Mak-Soon; Shin, Yoonjin; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

    2015-12-01

    Chronic low-grade inflammation is associated with obesity. This study investigated effect of high hydrostatic pressure extract of red ginseng (HRG) on inflammation in rats with high-fat (HF) diet induced obesity. Male, Sprague-Dawley rats (80~110 g) were randomly divided into two groups, and fed a 45% HF diet (HF) and a 45% HF diet containing 1.5% HRG (HF+HRG) for 14 weeks. At the end of the experiment, the serum leptin level was reduced by the HRG supplementation. The mRNA expression of genes related to adipogenesis including peroxisome proliferator-activated receptor-gamma and adipocyte protein 2 was down-regulated in the white adipose tissue (WAT). The mRNA levels of major inflammatory cytokines such as tumor necrosis factor-α, monocyte chemoattractant protein 1, and interleukin-6 were remarkably down-regulated by the HRG in WAT. These results suggest that HRG might be beneficial in ameliorating the inflammation-associated health complications by suppressing adipogenic and pro-inflammatory gene expression. PMID:26770912

  2. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats

    Directory of Open Access Journals (Sweden)

    Lee Si

    2011-07-01

    Full Text Available Abstract Background Recent studies have reported the preventive effects of probiotics on obesity. Among commensal bacteria, bifidobacteria is one of the most numerous probiotics in the mammalian gut and are a type of lactic acid bacteria. The aim of this study was to assess the antiobesity and lipid-lowering effects of Bifidobacterium spp. isolated from healthy Korean on high fat diet-induced obese rats. Methods Thirty-six male Sprague-Dawley rats were divided into three groups as follows: (1 SD group, fed standard diet; (2 HFD group, fed high fat diet; and (3 HFD-LAB group, fed high fat diet supplemented with LAB supplement (B. pseudocatenulatum SPM 1204, B. longum SPM 1205, and B. longum SPM 1207; 108 ~ 109 CFU. After 7 weeks, the body, organ, and fat weights, food intake, blood serum levels, fecal LAB counts, and harmful enzyme activities were measured. Results Administration of LAB reduced body and fat weights, blood serum levels (TC, HDL-C, LDL-C, triglyceride, glucose, leptin, AST, ALT, and lipase levels, and harmful enzyme activities (β-glucosidase, β-glucuronidase, and tryptophanase, and significantly increased fecal LAB counts. Conclusion These data suggest that Bifidobacterium spp. used in this study may have beneficial antiobesity effects.

  3. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.

    Science.gov (United States)

    Verdeguer, Francisco; Soustek, Meghan S; Hatting, Maximilian; Blättler, Sharon M; McDonald, Devin; Barrow, Joeva J; Puigserver, Pere

    2016-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  4. The Anti-Inflammatory Effect of Prunus yedoensis Bark Extract on Adipose Tissue in Diet-Induced Obese Mice

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    Hee Kang

    2015-01-01

    Full Text Available Chronic, low-grade inflammatory responses occur in obese adipose tissue and play a crucial role in the development of insulin resistance. Macrophages exposed to high glucose upregulate the expression of SRA, a macrophage-specific scavenger receptor. The present study investigated whether Prunus yedoensis (PY bark extract affects the inflammatory response and scavenger receptor gene expression observed in a diet-induced obesity model in vivo. Oral administration of PY extract significantly reduced fasting blood glucose levels without a change in body weight in mice fed a high fat diet for 17 weeks. PY extract significantly suppressed expression of inflammatory and macrophage genes such as tumor necrosis factor-α, interleukin-6, and F4/80 in epididymal adipose tissue. Among scavenger receptor genes, SRA expression was significantly reduced. The inhibitory responses of PY extract and its fractions were determined through evaluation of scavenger receptor expression in THP-1 cells. PY extract and its ethyl acetate fraction decreased the levels of SRA mRNA and phospho-ERK1/2 during monocyte differentiation. Our data indicate that the anti-inflammatory effects of PY extract and its downregulation of SRA seem to account for its hypoglycemic effects.

  5. Leptin activates oxytocin neurons of the hypothalamic paraventricular nucleus in both control and diet-induced obese rodents.

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    Mario Perello

    Full Text Available The adipocyte-derived hormone leptin acts in the brain to reduce body weight and fat mass. Recent studies suggest that parvocellular oxytocin (OXT neurons of the hypothalamic paraventricular nucleus (PVN can mediate body weight reduction through inhibition of food intake and increased energy expenditure. However, the role of OXT neurons of the PVN as a primary target of leptin has not been investigated. Here, we studied the potential role of OXT neurons of the PVN in leptin-mediated effects on body weight regulation in fasted rats. We demonstrated that intracerebroventricular (ICV leptin activates STAT3 phosphorylation in OXT neurons of the PVN, showed that this occurs in a subpopulation of OXT neurons that innervate the nucleus of the solitary tract (NTS, and provided further evidence suggesting a role of OXT to mediate leptin's actions on body weight. In addition, our results indicated that OXT neurons are responsive to ICV leptin and mediate leptin effects on body weight in diet induced obese (DIO rats, which are resistant to the anorectic effects of the hormone. Thus, we conclude that leptin targets a specific subpopulation of parvocellular OXT neurons of the PVN, and that this action may be important for leptin's ability to reduce body weight in both control and obese rats.

  6. Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats

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    Kathleen Kauter

    2013-02-01

    Full Text Available Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats.

  7. Lagenaria siceraria fruit extract ameliorate fat amassment and serum TNF-αin high-fat diet-induced obese rats

    Institute of Scientific and Technical Information of China (English)

    Sayyed Nadeem; Pradeep Dhore; Mohsin Quazi; Sunil Pawar; Navin Raj

    2012-01-01

    Objective:To investigate the effects of ethanolic extract ofLagenaria siceraria fruit(ELSF) on fat amassment and serumTNF-α in high-fat diet-induced obese rats.Methods:The high fat diet induced obese rats were orally treated with orlistat(50 mg/kg) andELSF(100,200,300 mg/kg/day) to the respective treatment groups.The body weight, fasting blood glucose level, lipid profile, serum levels of tumor necrosis factor-α(TNF-α) in rats were measured after30 days of treatment and compared to the obese control animals.Results:ELSF significantly(P <0.001) reduced the body weight gain, fasting blood glucose, total cholesterol, triglyceride, total protein andTNF-α.Conclusions:These encouraging findings suggest thatLagenaria siceraria has excellent pharmacological potential to prevent fat amassment.

  8. Lipidomic Analysis of Serum from High Fat Diet Induced Obese Mice

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    Kristina Eisinger

    2014-02-01

    Full Text Available Lipid metabolites regulate fatty acid and glucose homeostasis. The intention of the current study is to identify circulating lipid species, which are altered in rodent obesity and strongly correlate with the classically measured metabolites glucose, triglycerides, and cholesterol. Mice fed a high fat diet (HFD for 14 weeks have increased body weight and fasting glucose. Serum triglycerides are not altered, while cholesterol tends to be increased. Accordingly, major cholesteryl ester (CE species and free cholesterol are not significantly raised in obesity while minor metabolites, including CE 20:3 and CE 18:3, are increased or reduced, respectively. Distinct sphingomyelin (SM species are elevated while ceramides are not raised. Phosphatidylinositol (PI species, including PI 34:1, are raised while others are decreased. PI 34:1 strongly correlates with fasting glucose and proinsulin levels. Phosphatidylcholine (PC 26:0, 40:2, and 40:5, which are induced in obesity, correlate with cholesterol. PC 38:4 and PC 40:6 are also raised in fat fed mice and positively correlate with fasting glucose. Lysophosphatidylcholine (LPC species are also changed in obesity and the already shown reduction of LPC 16:1 has been confirmed. LPC 22:4, which is increased, correlates with serum cholesterol. The data indicate that circulating levels of various lipid species are changed in the obesity model studied and some of them are strongly associated with classically measured metabolites.

  9. Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats

    Science.gov (United States)

    Li, Mao; Ye, Ting; Wang, Xiao-Xia; Li, Xian; Qiang, Ou; Yu, Tao; Tang, Cheng-Wei; Liu, Rui

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) caused by liver lipid dysregulation is linked to obesity. Somatostatin (SST) and its analogs have been used to treat pediatric hypothalamic obesity. However, the application of such drugs for the treatment of NAFLD has not been evaluated. Objective This study aimed to investigate the expression levels of important regulators of hepatic lipid metabolism and the possible effect of the SST analog octreotide on these regulators. Methods SD rats were assigned to a control group and a high-fat diet group. Obese rats from the high-fat diet group were further divided into the obese and octreotide-treated groups. The body weight, plasma SST, fasting plasma glucose (FPG), insulin, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acid (FFA) levels were measured. Hepatic steatosis was evaluated based on the liver TG content, HE staining and oil red O staining. The SREBP-1c, ACC1, FAS, MTP, apoB and ADRP expression levels in the liver were also determined by RT-PCR, qRT-PCR, western blot or ELISA. Results The obese rats induced by high-fat diet expressed more SREBP-1c, FAS and ADRP but less MTP protein in the liver than those of control rats, whereas octreotide intervention reversed these changes and increased the level of apoB protein. Compared to the control group, obese rats showed increased liver ACC1, SREBP-1c and apoB mRNA levels, whereas octreotide-treated rats showed decreased mRNA levels of apoB and SREBP-1c. This was accompanied by increased body weight, liver TG contents, FPG, TG, TC, LDL-C, FFA, insulin and derived homeostatic model assessment (HOMA) values. Octreotide intervention significantly decreased these parameters. Compared to the control group, the obese group showed a decreasing trend on plasma SST levels, which were significantly increased by the octreotide intervention. Conclusion Octreotide can

  10. Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats.

    Directory of Open Access Journals (Sweden)

    Mao Li

    Full Text Available Non-alcoholic fatty liver disease (NAFLD caused by liver lipid dysregulation is linked to obesity. Somatostatin (SST and its analogs have been used to treat pediatric hypothalamic obesity. However, the application of such drugs for the treatment of NAFLD has not been evaluated.This study aimed to investigate the expression levels of important regulators of hepatic lipid metabolism and the possible effect of the SST analog octreotide on these regulators.SD rats were assigned to a control group and a high-fat diet group. Obese rats from the high-fat diet group were further divided into the obese and octreotide-treated groups. The body weight, plasma SST, fasting plasma glucose (FPG, insulin, triglyceride (TG, total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C and free fatty acid (FFA levels were measured. Hepatic steatosis was evaluated based on the liver TG content, HE staining and oil red O staining. The SREBP-1c, ACC1, FAS, MTP, apoB and ADRP expression levels in the liver were also determined by RT-PCR, qRT-PCR, western blot or ELISA.The obese rats induced by high-fat diet expressed more SREBP-1c, FAS and ADRP but less MTP protein in the liver than those of control rats, whereas octreotide intervention reversed these changes and increased the level of apoB protein. Compared to the control group, obese rats showed increased liver ACC1, SREBP-1c and apoB mRNA levels, whereas octreotide-treated rats showed decreased mRNA levels of apoB and SREBP-1c. This was accompanied by increased body weight, liver TG contents, FPG, TG, TC, LDL-C, FFA, insulin and derived homeostatic model assessment (HOMA values. Octreotide intervention significantly decreased these parameters. Compared to the control group, the obese group showed a decreasing trend on plasma SST levels, which were significantly increased by the octreotide intervention.Octreotide can ameliorate hepatic steatosis in obese rats

  11. High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity.

    Science.gov (United States)

    Denou, Emmanuel; Marcinko, Katarina; Surette, Michael G; Steinberg, Gregory R; Schertzer, Jonathan D

    2016-06-01

    Diet and exercise underpin the risk of obesity-related metabolic disease. Diet alters the gut microbiota, which contributes to aspects of metabolic disease during obesity. Repeated exercise provides metabolic benefits during obesity. We assessed whether exercise could oppose changes in the taxonomic and predicted metagenomic characteristics of the gut microbiota during diet-induced obesity. We hypothesized that high-intensity interval training (HIIT) would counteract high-fat diet (HFD)-induced changes in the microbiota without altering obesity in mice. Compared with chow-fed mice, an obesity-causing HFD decreased the Bacteroidetes-to-Firmicutes ratio and decreased the genetic capacity in the fecal microbiota for metabolic pathways such as the tricarboxylic acid (TCA) cycle. After HFD-induced obesity was established, a subset of mice were HIIT for 6 wk, which increased host aerobic capacity but did not alter body or adipose tissue mass. The effects of exercise training on the microbiota were gut segment dependent and more extensive in the distal gut. HIIT increased the alpha diversity and Bacteroidetes/Firmicutes ratio of the distal gut and fecal microbiota during diet-induced obesity. Exercise training increased the predicted genetic capacity related to the TCA cycle among other aspects of metabolism. Strikingly, the same microbial metabolism indexes that were increased by exercise were all decreased in HFD-fed vs. chow diet-fed mice. Therefore, exercise training directly opposed some of the obesity-related changes in gut microbiota, including lower metagenomic indexes of metabolism. Some host and microbial pathways appeared similarly affected by exercise. These exercise- and diet-induced microbiota interactions can be captured in feces. PMID:27117007

  12. Leptin resistance in diet-induced obesity : The role of hypothalamic inflammation

    NARCIS (Netherlands)

    de Git, K. C G; Adan, R. A H

    2015-01-01

    The consumption of Western diets, high in sugar and saturated fat, is a crucial contributor to the alarming incidence of obesity and its associated morbidities. These diets have been reported to induce an inflammatory response in the hypothalamus, which promotes the development of central leptin res

  13. Reversal of diet-induced obesity and insulin resistance by inducible genetic ablation of GRK2

    NARCIS (Netherlands)

    Vila-Bedmar, Rocio; Cruces-Sande, Marta; Lucas, Elisa; Willemen, Hanneke L D M; Heijnen, Cobi J; Kavelaars, Annemieke; Mayor, Federico; Murga, Cristina

    2015-01-01

    Insulin resistance is a common feature of obesity and predisposes individuals to various prevalent pathological conditions. G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor kinase 2 (GRK2) integrates several signal transduction pathways and is emerging as a physiologica

  14. Effects of four Bifidobacteria on obesity in high-fat diet induced rats

    OpenAIRE

    Yin, Ya-Ni; Yu, Qiong-Fen; Fu, Nian; LIU, XIAO-WEI; Lu, Fang-Gen

    2010-01-01

    AIM: To compare the effects of four Bifidobacteria strains (Bifidobacteria L66-5, L75-4, M13-4 and FS31-12, originated from normal human intestines) on weight gain, lipid metabolism, glucose metabolism in an obese murine model induced by high-fat diet.

  15. Increased susceptibility to diet-induced obesity in histamine-deficient mice

    DEFF Research Database (Denmark)

    Jørgensen, Emilie A; Vogelsang, Thomas W; Knigge, Ulrich;

    2006-01-01

    in the development of high-fat diet (HFD)-induced obesity. METHODS: Histamine-deficient histidine decarboxylase knock-out (HDC-KO) mice and C57BL/6J wild-type (WT) mice were given either a standard diet (STD) or HFD for 8 weeks. Body weight, 24-hour caloric intake, epididymal adipose tissue size...

  16. An obligatory role for neurotensin in high-fat-diet-induced obesity.

    Science.gov (United States)

    Li, Jing; Song, Jun; Zaytseva, Yekaterina Y; Liu, Yajuan; Rychahou, Piotr; Jiang, Kai; Starr, Marlene E; Kim, Ji Tae; Harris, Jennifer W; Yiannikouris, Frederique B; Katz, Wendy S; Nilsson, Peter M; Orho-Melander, Marju; Chen, Jing; Zhu, Haining; Fahrenholz, Timothy; Higashi, Richard M; Gao, Tianyan; Morris, Andrew J; Cassis, Lisa A; Fan, Teresa W-M; Weiss, Heidi L; Dobner, Paul R; Melander, Olle; Jia, Jianhang; Evers, B Mark

    2016-05-19

    Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually and are among the most prevalent and challenging conditions confronting the medical profession. Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine and released by fat ingestion, facilitates fatty acid translocation in rat intestine, and stimulates the growth of various cancers. The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively). Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality; however, a role for NT as a causative factor in these diseases is unknown. Here we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin). Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and

  17. Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice.

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    Bin Feng

    Full Text Available BACKGROUND: Obesity-related adipose inflammation has been thought to be a causal factor for the development of insulin resistance and type 2 diabetes. Infiltrated macrophages in adipose tissue of obese animals and humans are an important source for inflammatory cytokines. Clodronate liposomes can ablate macrophages by inducing apoptosis. In this study, we aim to determine whether peritoneal injection of clodronate liposomes has any beneficial effect on systemic glucose homeostasis/insulin sensitivity and whether macrophage content in visceral adipose tissue will be reduced in diet-induced obese (DIO mice. METHODOLOGY/PRINCIPAL FINDINGS: Clodronate liposomes were used to deplete macrophages in lean and DIO mice. Macrophage content in visceral adipose tissue, metabolic parameters, glucose and insulin tolerance, adipose and liver histology, adipokine and cytokine production were examined. Hyperinsulinemic-euglycemic clamp study was also performed to assess systemic insulin sensitivity. Peritoneal injection of clodronate liposomes significantly reduced blood glucose and insulin levels in DIO mice. Systemic glucose tolerance and insulin sensitivity were mildly improved in both lean and DIO mice treated with clodronate liposomes by intraperitoneal (i.p. injection. Hepatosteatosis was dramatically alleviated and suppression of hepatic glucose output was markedly increased in DIO mice treated with clodronate liposomes. Macrophage content in visceral adipose tissue of DIO mice was effectively decreased without affecting subcutaneous adipose tissue. Interestingly, levels of insulin sensitizing hormone adiponectin, including the high molecular weight form, were significantly elevated in circulation. CONCLUSIONS/SIGNIFICANCE: Intraperitoneal injection of clodronate liposomes reduces visceral adipose tissue macrophages, improves systemic glucose homeostasis and insulin sensitivity in DIO mice, which can be partially attributable to increased adiponectin

  18. Effect of Antioxidants Supplementation or Restricted Diet on Oxidative Stress in a Rat Model of Diet-Induced Obesity

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    A.A. Vahidinia

    2011-04-01

    Full Text Available Introduction & Objective: Obesity is independently associated with increased oxidative stress in men and women. Natural antioxidants showed substantial antioxidative and anti-inflammatory activities in vivo. The aim of this study was to examine the preventive effect of antioxidant supplements and/or restricted diet on the stress oxidative index (8-Iso-PGF2α and total antioxidant capacity (TAC in obese rats induced by a high-fat (HF diet. Material and Methods: In this experimental study forty-eight male Wister rats were randomly assigned to HF purified diet (61% kcal from fat ad libitum, HF restricted (30%, HF supplemented with astaxanthin, vitamin E and C (HFS, HFS restricted (30% for 12 weeks. Their daily food intake and weekly body weight gain were measured. Serum 8-Iso-PGF2α and TAC measured by EIA methods. Results: Energy intake was not significant in HF with HFS (58.8 and 58.6 kcal/rat/d, respectively and in HF restricted with HFS restricted (41.7 and 41.6 kcal/rat/d, respectively. Serum 8-Iso-PGF2α in HF was 1416.2±443.5 and in HF restricted was 1209.4±424.4pg/ml (p>0.05 and equal for other groups. The lowest TAC was seen in HF and highest was in HFS (0.36±0.43 and 3.0±1.13 mM, respectively (p<0.001. Conclusions: These results suggest that antioxidant supplements and caloric restriction may improved TAC and partially suppress stress oxidative index in high fat diet induced obese rats. (Sci J Hamadan Univ Med Sci 2011;18(1:48-56

  19. Green tea extract suppresses adiposity and affects the expression of lipid metabolism genes in diet-induced obese zebrafish

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    Hasumura Takahiro

    2012-08-01

    Full Text Available Abstract Background Visceral fat accumulation is one of the most important predictors of mortality in obese populations. Administration of green tea extract (GTE can reduce body fat and reduce the risk of obesity-related diseases in mammals. In this study, we investigated the effects and mechanisms of GTE on adiposity in diet-induced obese (DIO zebrafish. Methods Zebrafish at 3.5 to 4.5 months post-fertilization were allocated to four groups: non-DIO, DIO, DIO + 0.0025%GTE, and DIO + 0.0050%GTE. The non-DIO group was fed freshly hatched Artemia once daily (5 mg cysts/fish daily for 40 days. Zebrafish in the three DIO groups were fed freshly hatched Artemia three times daily (60 mg cysts/fish daily. Zebrafish in the DIO + 0.0025%GTE and DIO + 0.0050%GTE groups were exposed to GTE after the start of feeding three times daily for 40 days. Results Three-dimensional microcomputed tomography analysis showed that GTE exposure significantly decreased the volume of visceral but not subcutaneous fat tissue in DIO zebrafish. GTE exposure increased hepatic expression of the lipid catabolism genes ACOX1 (acyl-coenzyme A oxidase 1, palmitoyl, ACADM (acyl-coenzyme A dehydrogenase, c-4 to c-12 straight chain, and PPARA (peroxisome proliferator-activated receptor alpha. GTE exposure also significantly decreased the visceral fat expression of SOCS3 (suppressor of cytokine signaling 3b which inhibits leptin signaling. Conclusions The present results are consistent with those seen in mammals treated with GTE, supporting the validity of studying the effects of GTE in DIO zebrafish. Our results suggest that GTE exerts beneficial effects on adiposity, possibly by altering the expression of lipid catabolism genes and SOCS3.

  20. Depot-specific effects of treadmill running and rutin on white adipose tissue function in diet-induced obese mice.

    Science.gov (United States)

    Chen, Neng; Lei, Ting; Xin, Lili; Zhou, Lingmei; Cheng, Jinbo; Qin, Liqiang; Han, Shufen; Wan, Zhongxiao

    2016-09-01

    White adipose tissue (WAT) is a critical organ involved in regulating metabolic homeostasis under obese condition. Strategies that could positively affect WAT function would hold promise for fighting against obesity and its complications. The aim of the present study is to explore the effects of treadmill exercise training and rutin intervention on adipose tissue function from diet-induced obese (DIO) mice and whether fat depot-specific effects existed. In epididymal adipose tissue, high-fat diet (HFD) resulted in reduction in adiponectin mRNA expression, peroxisome proliferator-activated receptors (PPAR)-γ and DsbA-L protein expression, elevation in endoplasmic reticulum (ER) stress markers including 78 kDa glucose-regulated protein (GRP-78), C/EBP homologous protein (CHOP) and p-c-Jun N-terminal kinase (JNK). Isoproterenol-stimulated lipolysis and insulin stimulated Akt phosphorylation ex vivo were blunted from HFD group. The combination of rutin with exercise (HRE) completely restored GRP78 and p-JNK protein expression to normal levels, as well as blunted signaling ex vivo. In inguinal adipose tissue, HFD led to increased adiponectin mRNA expression, PPAR-γ, GRP78, and p-JNK protein expression, and reduction in DsbA-L. HRE is effective for restoring p-JNK, PPAR-γ, and DsbA-L. In conclusion, depot-specific effects may exist in regard to the effects of rutin and exercise on key molecules involved in regulating adipose tissue function (i.e., ER stress markers, PPAR-γ and DsbA-L, adiponectin expression, and secretion, ex vivo catecholamine stimulated lipolysis and insulin stimulated Akt phosphorylation) from DIO mice. PMID:27192989

  1. Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity.

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    Alessandro Marsili

    Full Text Available BACKGROUND: The type 2 iodothyronine deiodinase (D2 converts the pro-hormone thyroxine into T3 within target tissues. D2 is essential for a full thermogenic response of brown adipose tissue (BAT, and mice with a disrupted Dio2 gene (D2KO have an impaired response to cold. BAT is also activated by overfeeding. METHODOLOGY/PRINCIPAL FINDINGS: After 6-weeks of HFD feeding D2KO mice gained 5.6% more body weight and had 28% more adipose tissue. Oxygen consumption (V0(2 was not different between genotypes, but D2KO mice had an increased respiratory exchange ratio (RER, suggesting preferential use of carbohydrates. Consistent with this, serum free fatty acids and β-hydroxybutyrate were lower in D2KO mice on a HFD, while hepatic triglycerides were increased and glycogen content decreased. Neither genotype showed glucose intolerance, but D2KO mice had significantly higher insulin levels during GTT independent of diet. Accordingly, during ITT testing D2KO mice had a significantly reduced glucose uptake, consistent with insulin resistance. Gene expression levels in liver, muscle, and brown and white adipose tissue showed no differences that could account for the increased weight gain in D2KO mice. However, D2KO mice have higher PEPCK mRNA in liver suggesting increased gluconeogenesis, which could also contribute to their apparent insulin resistance. CONCLUSIONS/SIGNIFICANCE: We conclude that the loss of the Dio2 gene has significant metabolic consequences. D2KO mice gain more weight on a HFD, suggesting a role for D2 in protection from diet-induced obesity. Further, D2KO mice appear to have a greater reliance on carbohydrates as a fuel source, and limited ability to mobilize and to burn fat. This results in increased fat storage in adipose tissue, hepatic steatosis, and depletion of liver glycogen in spite of increased gluconeogenesis. D2KO mice are also less responsive to insulin, independent of diet-induced obesity.

  2. Early cardiovascular changes occurring in diet-induced, obese insulin-resistant rats.

    Science.gov (United States)

    Huisamen, Barbara; Dietrich, Daneel; Bezuidenhout, Nicole; Lopes, John; Flepisi, Brian; Blackhurst, Dee; Lochner, Amanda

    2012-09-01

    The metabolic syndrome is recognized as a cluster of disturbances associated with obesity, type 2 diabetes and hypertension. Over the past two decades, the number of people with the metabolic syndrome has increased at an alarming rate. This increase is associated with the global epidemic of both obesity and diabetes. Cardiovascular mortality is increased among diabetics and obesity-related insulin-resistant patients, and obesity is currently recognized as independent risk factor for cardiovascular disease. We aimed to establish the effects of a short period of an altered diet on the heart using a rat model of hyperphagia-induced obesity (diet supplemented with sucrose and condensed milk for 8 weeks = DIO) compared to age-matched controls. Isolated, perfused hearts were subjected to global or regional ischaemia/reperfusion. Function on reperfusion was recorded and infarct size determined. A plasma lipid profile was established via HPLC-based methods and proteins involved in metabolic signalling determined either by western blotting or RT-PCR. 8 weeks of diet resulted in whole-body but not myocardial insulin resistance, increased plasma triglyceride and phospholipid levels as well as increased lipid peroxidation. Despite the similar baseline function, hearts from DIO animals showed significantly poorer postischaemic recovery than controls (41.9 % RPP recovery vs 57.9 %, P < 0.05, n = 7-11/group) but surprisingly, smaller infarct size (24.95 ± 1.97 vs 47.26 ± 4.05 % of the area at risk, P < 0.005, n = 8/group). Basal phosphorylation of PKB/Akt was elevated but IRS-1 and SERCA-2 expression severely downregulated. In conclusion, after only 8 weeks of a slight change in diet, the rat heart shows signs of metabolic remodelling. Some of these changes may be protective but others may be detrimental and eventually lead to maladaptation. PMID:22638648

  3. Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity.

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    Shih-Lung Woo

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is closely associated with obesity and insulin resistance. To better understand the pathophysiology of obesity-associated NAFLD, the present study examined the involvement of liver and adipose tissues in metformin actions on reducing hepatic steatosis and inflammation during obesity. C57BL/6J mice were fed a high-fat diet (HFD for 12 weeks to induce obesity-associated NAFLD and treated with metformin (150 mg/kg/d orally for the last four weeks of HFD feeding. Compared with HFD-fed control mice, metformin-treated mice showed improvement in both glucose tolerance and insulin sensitivity. Also, metformin treatment caused a significant decrease in liver weight, but not adiposity. As indicated by histological changes, metformin treatment decreased hepatic steatosis, but not the size of adipocytes. In addition, metformin treatment caused an increase in the phosphorylation of liver AMP-activated protein kinase (AMPK, which was accompanied by an increase in the phosphorylation of liver acetyl-CoA carboxylase and decreases in the phosphorylation of liver c-Jun N-terminal kinase 1 (JNK1 and in the mRNA levels of lipogenic enzymes and proinflammatory cytokines. However, metformin treatment did not significantly alter adipose tissue AMPK phosphorylation and inflammatory responses. In cultured hepatocytes, metformin treatment increased AMPK phosphorylation and decreased fat deposition and inflammatory responses. Additionally, in bone marrow-derived macrophages, metformin treatment partially blunted the effects of lipopolysaccharide on inducing the phosphorylation of JNK1 and nuclear factor kappa B (NF-κB p65 and on increasing the mRNA levels of proinflammatory cytokines. Taken together, these results suggest that metformin protects against obesity-associated NAFLD largely through direct effects on decreasing hepatocyte fat deposition and on inhibiting inflammatory responses in both hepatocytes and macrophages.

  4. Serum growth hormone-binding protein in obesity: effect of a short-term, very low calorie diet and diet-induced weight loss

    DEFF Research Database (Denmark)

    Rasmussen, M H; Ho, K K; Kjems, L;

    1996-01-01

    positively correlated to insulin as well as proinsulin levels (r = 0.60; P < 0.001 and r = 0.55; P < 0.001, respectively). After diet-induced massive weight loss, GHBP levels were restored to normal in obese subjects (BMI, 27.8 +/- 1.4 kg/m2). Multiple stepwise regression analysis revealed that changes in...... waist circumference and abdominal sagittal diameter during weight loss were the major determinants of and accounted for 54% of the fall in GHBP levels. Neither insulin nor proinsulin was an independent predictor. No changes were observed in GHBP in normal, obese, or reduced weight obese subjects after 4...

  5. Triterpene alcohols and sterols from rice bran lower postprandial glucose-dependent insulinotropic polypeptide release and prevent diet-induced obesity in mice.

    Science.gov (United States)

    Fukuoka, Daisuke; Okahara, Fumiaki; Hashizume, Kohjiro; Yanagawa, Kiyotaka; Osaki, Noriko; Shimotoyodome, Akira

    2014-12-01

    Obesity is now a worldwide health problem. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone that is secreted following the ingestion of food and modulates energy metabolism. Previous studies reported that lowering diet-induced GIP secretion improved energy homeostasis in animals and humans, and attenuated diet-induced obesity in mice. Therefore, food-derived GIP regulators may be used in the development of foods that prevent obesity. Rice bran oil and its components are known to have beneficial effects on health. Therefore, the aim of the present study was to clarify the effects of the oil-soluble components of rice bran on postprandial GIP secretion and obesity in mice. Triterpene alcohols [cycloartenol (CA) and 24-methylene cycloartanol (24Me)], β-sitosterol, and campesterol decreased the diet-induced secretion of GIP in C57BL/6J mice. Mice fed a high-fat diet supplemented with a triterpene alcohol and sterol preparation (TASP) from rice bran for 23 wk gained less weight than control mice. Indirect calorimetry revealed that fat utilization was higher in TASP-fed mice than in control mice. Fatty acid oxidation-related gene expression in the muscles of mice fed a TASP-supplemented diet was enhanced, whereas fatty acid synthesis-related gene expression in the liver was suppressed. The treatment of HepG2 cells with CA and 24Me decreased the gene expression of sterol regulatory element-binding protein (SREBP)-1c. In conclusion, we clarified for the first time that triterpene alcohols and sterols from rice bran prevented diet-induced obesity by increasing fatty acid oxidation in muscles and decreasing fatty acid synthesis in the liver through GIP-dependent and GIP-independent mechanisms. PMID:25257874

  6. Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway

    OpenAIRE

    Vernia, Santiago; Cavanagh-Kyros, Julie; Barrett, Tamera; Jung, Dae Young; Kim, Jason K.; Davis, Roger J

    2013-01-01

    JNK signaling mediates metabolic stress responses caused by a high-fat diet. Vernia et al. find that mice lacking Jnk genes in the anterior pituitary gland exhibit increased pituitary expression of TSH, increased blood concentration of thyroid hormone (T4), increased energy expenditure, and reduced obesity. The increase in pituitary TSH was caused by reduced expression of type 2 iodothyronine deiodinase (Dio2). These results provide a mechanism through which JNK regulates energy expenditure a...

  7. Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice.

    Science.gov (United States)

    Naowaboot, Jarinyaporn; Wannasiri, Supaporn; Pannangpetch, Patchareewan

    2016-06-01

    Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFD-induced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities. PMID:26976296

  8. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice

    OpenAIRE

    Keung, Wendy; Ussher, John R.; Jaswal, Jagdip S.; Raubenheimer, Monique; Lam, Victoria H.M.; Wagg, Cory S.; Lopaschuk, Gary D

    2013-01-01

    Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated what effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice were fed a high-f...

  9. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity

    OpenAIRE

    Kraus, Daniel; Yang, Qin; Kong, Dong; Banks, Alexander S.; Zhang, Lin; Rodgers, Joseph T; Pirinen, Eija; Pulinilkunnil, Thomas C.; Gong, Fengying; Wang, Ya-chin; Cen, Yana; Sauve, Anthony A.; Asara, John M.; Peroni, Odile D.; Monia, Brett P.

    2014-01-01

    In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes1. Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity2. Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue (WAT) from adipose-specific Glut4-knockout or adipose-specific Glut4-overexpressing mice with their respect...

  10. Exercise during pregnancy protects adult mouse offspring from diet-induced obesity

    OpenAIRE

    Wasinski, F.; Bacurau, R.F.P.; Estrela, G.R.; Klempin, F.; Arakaki, A.M.; Batista, R.O.; Mafra, F.F.P.; do Nascimento, L.F.R.; M.I. Hiyane; L.A. Velloso; N.O.S. Camara; Araujo, R C

    2015-01-01

    Background Physical exercise induces positive alterations in gene expression involved in the metabolism of obesity. Maternal exercise provokes adaptations soon after birth in the offspring. Here, we investigated whether adult mouse offspring of swim-trained mothers is protected against the development of the deleterious effects of high fat diet (HFD). Methods Our study comprises two parts. First, female C57BL/6 mice were divided into one sedentary and one swim-trained group (before and during...

  11. The Effects of Voluntary Exercise on Oocyte Quality in a Diet-Induced Obese Murine Model

    OpenAIRE

    Boudoures, Anna L.; Chi, Maggie; Thompson, Alysha; Zhang, Wendy; Moley, Kelle H.

    2015-01-01

    Obesity negatively affects many aspects of the human body, including reproductive function. In females, the root of the decline in fertility is linked to problems in the oocyte. Problems seen in oocytes that positively correlate with increasing BMI include changes to the metabolism, lipid accumulation, meiosis, and metaphase II (MII) spindle structure. Studies in mice indicate dietary interventions fail to reverse these problems [4]. How exercise affects the oocytes has not been addressed. Th...

  12. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality

    OpenAIRE

    Boon, M.R.; Berg, S.A.A. van den; Wang, Y; Bossche, J. van den; Karkampouna, S.; Bauwens, M.; Saint-Hubert, M. de; Horst, G; Vukicevic, S.; de Winther, M. P. J.; Havekes, L M; Jukema, J.W.; Tamsma, J. T.; Pluijm, G. van der; van Dijk, K W

    2013-01-01

    Background/Aims:Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7...

  13. IEX-1 deficiency induces browning of white adipose tissue and resists diet-induced obesity

    OpenAIRE

    Mohd. Shahid; Ammar A. Javed; David Chandra; Haley E. Ramsey; Dilip Shah; Khan, Mohammed F.; Liping Zhao; Mei X. Wu

    2016-01-01

    Chronic inflammation plays a crucial role in the pathogenesis of obesity and insulin resistance. However, the primary mediators that affect energy homeostasis remain ill defined. Here, we report an unexpected role for immediate early response gene X-1 (IEX-1), a downstream target of NF-κB, in energy metabolism. We found that IEX-1 expression was highly induced in white adipose tissue (WAT) in both epidydmal and subcutaneous depots but not in interscapular brown adipose tissue (BAT) in mice fe...

  14. Altered Energy Homeostasis and Resistance to Diet-Induced Obesity in KRAP-Deficient Mice

    OpenAIRE

    Fujimoto, Takahiro; Miyasaka, Kyoko; Koyanagi, Midori; Tsunoda, Toshiyuki; Baba, Iwai; Doi, Keiko; Ohta, Minoru; Kato, Norihiro; Sasazuki, Takehiko; Shirasawa, Senji

    2009-01-01

    Obesity and related metabolic disorders have become leading causes of adult morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule, however, its physiological roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP−/− ) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia....

  15. Diet-Induced Obesity Prevents Interstitial Dispersion of Insulin in Skeletal Muscle

    OpenAIRE

    Kolka, Cathryn M; Harrison, L. Nicole; Lottati, Maya; Chiu, Jenny D.; Kirkman, Erlinda L.; Bergman, Richard N

    2009-01-01

    OBJECTIVE Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to cause glucose uptake. When insulin resistance is induced by exogenous lipid infusion, this interstitial diffusion process is curtailed. Thus, the possibility exists that hyperlipide...

  16. Increased Myocardial Susceptibility to Repetitive Ischemia with High-Fat–Diet-Induced Obesity

    OpenAIRE

    Thakker, Geeta D; Frangogiannis, Nikolaos G; Zymek, Pawel T.; Sharma, Saumya; Raya, Joe L.; Barger, Philip M.; Taegtmeyer, Heinrich; Entman, Mark L.; Ballantyne, Christie M

    2008-01-01

    Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dys...

  17. Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats.

    Science.gov (United States)

    Castro, Gisele; C Areias, Maria Fernanda; Weissmann, Lais; Quaresma, Paula G F; Katashima, Carlos K; Saad, Mario J A; Prada, Patricia O

    2013-01-01

    Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala. PMID:24251109

  18. Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats☆

    Science.gov (United States)

    Castro, Gisele; C. Areias, Maria Fernanda; Weissmann, Lais; Quaresma, Paula G.F.; Katashima, Carlos K.; Saad, Mario J.A.; Prada, Patricia O.

    2013-01-01

    Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala. PMID:24251109

  19. Diet-Induced Obesity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

    Directory of Open Access Journals (Sweden)

    Suvi T. Ruohonen

    2012-01-01

    Full Text Available Neuropeptide Y (NPY is a neurotransmitter associated with feeding and obesity. We have constructed an NPY transgenic mouse model (OE- mouse, where targeted overexpression leads to increased levels of NPY in noradrenergic and adrenergic neurons. We previously showed that these mice become obese on a normal chow. Now we aimed to study the effect of a Western-type diet in OE- and wildtype (WT mice, and to compare the genotype differences in the development of obesity, insulin resistance, and diabetes. Weight gain, glucose, and insulin tolerance tests, fasted plasma insulin, and cholesterol levels were assayed. We found that female OE- mice gained significantly more weight without hyperphagia or decreased activity, and showed larger white and brown fat depots with no difference in UCP-1 levels. They also displayed impaired glucose tolerance and decreased insulin sensitivity. OE- and WT males gained weight robustly, but no difference in the degree of adiposity was observed. However, 40% of but none of the WT males developed hyperglycaemia while on the diet. The present study shows that female OE- mice were not protected from the obesogenic effect of the diet suggesting that increased NPY release may predispose females to a greater risk of weight gain under high caloric conditions.

  20. Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice.

    Science.gov (United States)

    Park, Byong-Gon; Park, Yoon-Sun; Park, Joo Woong; Shin, Eunji; Shin, Woon-Seob

    2016-04-22

    Hyaluronan has diverse biological activities depending on its molecular size. The hyaluronan fragments (50 kDa) can decrease adipogenic differentiation in vitro. However, in vivo anti-obesitic effects of hyaluronan fragments have not been elucidated. Therefore, we examined the anti-obesity effects of hyaluronan fragments on high-fat diet induced obesity in C57BL/6 mice. Oral administration of hyaluronan fragments (200 mg/kg for 8 weeks) decreased body weight, adipose tissues, serum lipid (low-density lipoprotein cholesterol, triglyceride), and leptin level. Hyaluronan fragments decreased the hypertrophy of adipose tissue and ameliorated liver steatosis. The mRNA expression of leptin was reduced in adipocyte by treatment with hyaluronan fragments. Additionally, hyaluronan fragments enhanced the mRNA expression of PPAR-α and its target genes UCP-2 and decreased mRNA expression of PPAR- γ and fatty acid synthase in liver. In conclusions, hyaluronan fragments had marked effects on inhibiting the development of obesity in obese mice fed the high-fat diet. It suggested that enhancing PPAR-α and suppressing PPAR-γ expression are two possible mechanisms for the anti-obesitic effect of hyaluronan fragments. PMID:27012203

  1. The tissue distribution of recombinant adiponectin in type 2 diabetic mice and diet-induced obesity mice

    International Nuclear Information System (INIS)

    To investigate the tissue distribution of 125I labeled adiponectin recombinant globular form (125I-gAcrp) in Diet-induced obesity (DIO) mice, type 2 diabetes mellitus (T2DM) mice and normal mice. 125I-gAcrp was prepared and injected into different types of mice through the veins of tails, and then the radio-counts in brain, glandular angularis, heart, lung, liver, spleen, stomach, intestine, adipose tissue, kidney, muscle, testis, uterus and blood were measured at 0.5 and 2 h, respectively. The results showed that 125I-gAcrp has a much higher uptake at 2 h in the liver of T2DM mice and in the glandular angularis of DIO mice than that of at 0.5 h, whilst it has a lower uptake in the liver of DIO mice at 2 h, and also the uptake of 125I- gAcrp in the stomach, intestine and testis of DIO mice and in uterus of T2DM mice groups were increased. The result indicated that glandular angularis, testis and uterus probably play roles in the process of fat metabolism and blood glucose regulation of adiponectin in DIO and T2DM mice, besides liver and muscle. (authors)

  2. Skeletal Muscle Mitochondrial Bioenergetics and Morphology in High Fat Diet Induced Obesity and Insulin Resistance: Focus on Dietary Fat Source.

    Science.gov (United States)

    Putti, Rosalba; Migliaccio, Vincenzo; Sica, Raffaella; Lionetti, Lillà

    2015-01-01

    It has been suggested that skeletal muscle mitochondria play a key role in high fat (HF) diet induced insulin resistance (IR). Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle IR. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to IR. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of IR. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift toward mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and IR development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle IR and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle IR, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance. PMID:26834644

  3. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-04-01

    Full Text Available Human embryonic stem cell (hESC-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  4. Effect of Ethanolic Extract of Fragaria Vesca on serum glucose levels and body weight in diet induced obese rats

    Directory of Open Access Journals (Sweden)

    Venkat ramana Yella

    2015-10-01

    Full Text Available Objective: to evaluate the effect of ethanolic extract Fragaria Vesca on serum glucose levels in diet induced obese rats.Material and methods: Male Wister albino rats weighing 200- 250 gm, were divided into 3 groups of 6 animals each. The animals of all the groups except normal group were given a lipid diet consisting of cholesterol (1%, cholic acid (0.5%, casein (20%, choline (0.25%, d-l-methionin1(0.4%, coconut oil (25%, multi vitamin mix (3.5% and sucrose (48.4% with standard pellet diet for 30 days [20]. Growth rate was monitored during the treatment. Results: There was significantly decrease in blood glucose in standard group compared to HFD model (P< 0.05.  But there was no significant change among other groupsConclusion:  There was no significant change in the blood glucose level in all the groups except the standard group, but there was reduction in body weight.

  5. Skeletal muscle mitochondrial bioenergetics and morphology in high fat diet induced obesity and insulin resistance: focus on dietary fat source

    Directory of Open Access Journals (Sweden)

    Rosalba ePutti

    2016-01-01

    Full Text Available It has been suggested that skeletal muscle mitochondria play a key role in high fat diet induced insulin resistance. Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle insulin resistance. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to insulin resistance. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of insulin resistance. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift towards mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and insulin resistance development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle insulin resistance and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle insulin resistance, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance.

  6. Antiobesity Effect of Codonopsis lanceolata in High-Calorie/High-Fat-Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Hye-Kyung Choi

    2013-01-01

    Full Text Available The antiobesity effects of Codonopsis lanceolata (CL were evaluated in a high-calorie/high-fat-diet (HFD- induced obesity rat model and 3T3-L1 cells. The Sprague-Dawley male rats were fed a normal diet (ND or a HFD for a period of 12 weeks. The rats were subdivided into groups: ND, ND + wild Codonopsis lanceolata (wCL (900 mg/kg/day, p.o., ND + cultivated Codonopsis lanceolata (cCL (900 mg/kg/day, p.o., HFD, HFD + wCL (100, 300, or 900 mg/kg/day, p.o., HFD + cCL (100, 300, or 900 mg/kg/day, p.o., and HFD + sibutramine. The body weight gains of the administered HFD + CL (wCL or CCL were lower than those of the rats fed with only the HFD group. Moreover, the weight of adipose pads and the serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol in the group administered HDL + CL were significantly lower than in the HFD group. The inhibitory effect of lipid accumulation in 3T3-L1 cells was measured by Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR. Treatment of 3T3-L1 cells with wCL inhibited lipid accumulation and expression of C/EBPα and PPARγ. These results suggest that CL has a great potential as a functional food with anti-obesity effects and as a therapeutic alternative in the treatment of obesity.

  7. CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity.

    Science.gov (United States)

    Cao, Li; Qin, Xing; Peterson, Matthew R; Haller, Samantha E; Wilson, Kayla A; Hu, Nan; Lin, Xin; Nair, Sreejayan; Ren, Jun; He, Guanglong

    2016-03-01

    Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL-6, IL-1β and TNFα. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart. PMID

  8. RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders

    OpenAIRE

    Valérie Grandjean; Sandra Fourré; Diana Andrea Fernandes De Abreu; Marie-Alix Derieppe; Jean-Jacques Remy; Minoo Rassoulzadegan

    2015-01-01

    The paternal heredity of obesity and diabetes induced by a high-fat and/or high-sugar diet (Western-like diet) has been demonstrated through epidemiological analysis of human cohorts and experimental analysis, but the nature of the hereditary vector inducing this newly acquired phenotype is not yet well defined. Here, we show that microinjection of either testis or sperm RNA of male mice fed a Western-like diet into naive one-cell embryos leads to the establishment of the Western-like diet-in...

  9. Differential Development of Glucose Intolerance and Pancreatic Islet Adaptation in Multiple Diet Induced Obesity Models

    OpenAIRE

    Bo Ahrén; Giovanni Pacini; Bilal Omar

    2012-01-01

    Background: The C57BL/6 mouse fed a high fat diet is a common and valuable model in experimental studies of obesity and type 2 diabetes (T2D). Different high fat diets are used and in order to determine which diet produces a model most accurately resembling human T2D, they need to be compared head-to-head. Methods: Four different diets, the 60% high fat diet (HFD) and the 58% high fat-high sucrose Surwit diet (HFHS) and their respective controls, were compared in C57BL/6J mice using glucose t...

  10. Effects of four Bifidobacteria on obesity in high-fat diet induced rats

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To compare the effects of four Bifidobacteria strains(Bifidobacteria L66-5,L75-4,M13-4 and FS31-12,originated from normal human intestines) on weight gain,lipid metabolism,glucose metabolism in an obese murine model induced by high-fat diet.METHODS:Forty-eight Sprague-Dawley rats were randomly divided into six groups.Control group received standard chow,model group received high-fat diet,and intervention groups received high-fat diet added with different Bifidobacteria strains isolated from healthy volu...

  11. Increased susceptibility to diet-induced obesity in GPRC6A receptor knockout mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Madsen, Andreas N;

    2013-01-01

    significant increase in body weight, corresponding to a selective increase in body fat, was observed in Gprc6a KO mice exposed to an HFD relative to WT controls. The obese phenotype was linked to subtle perturbations in energy homoeostasis as GPRC6A deficiency resulted in chronic hyperphagia and decreased...... glucose metabolism showing that Gprc6a KO mice on an HFD display increased susceptibility to develop metabolic-related disorders. Altogether, these data suggest that the amino acid sensing receptor GPRC6A plays an important role in resistance to DIO and metabolic complications. Future studies will...

  12. Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57BL/6J mice.

    Directory of Open Access Journals (Sweden)

    Regan Roat

    Full Text Available The reduction of functional β cell mass is a key feature of type 2 diabetes. Here, we studied metabolic functions and islet gene expression profiles of C57BL/6J mice with naturally occurring nicotinamide nucleotide transhydrogenase (NNT deletion mutation, a widely used model of diet-induced obesity and diabetes. On high fat diet (HF, the mice developed obesity and hyperinsulinemia, while blood glucose levels were only mildly elevated indicating a substantial capacity to compensate for insulin resistance. The basal serum insulin levels were elevated in HF mice, but insulin secretion in response to glucose load was significantly blunted. Hyperinsulinemia in HF fed mice was associated with an increase in islet mass and size along with higher BrdU incorporation to β cells. The temporal profiles of glucose-stimulated insulin secretion (GSIS of isolated islets were comparable in HF and normal chow fed mice. Islets isolated from HF fed mice had elevated basal oxygen consumption per islet but failed to increase oxygen consumption further in response to glucose or carbonyl cyanide-4-trifluoromethoxyphenylhydrazone (FCCP. To obtain an unbiased assessment of metabolic pathways in islets, we performed microarray analysis comparing gene expression in islets from HF to normal chow-fed mice. A few genes, for example, those genes involved in the protection against oxidative stress (hypoxia upregulated protein 1 and Pgc1α were up-regulated in HF islets. In contrast, several genes in extracellular matrix and other pathways were suppressed in HF islets. These results indicate that islets from C57BL/6J mice with NNT deletion mutation develop structural, metabolic and gene expression features consistent with compensation and decompensation in response to HF diet.

  13. A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice.

    Science.gov (United States)

    Ohyama, Kana; Nogusa, Yoshihito; Suzuki, Katsuya; Shinoda, Kosaku; Kajimura, Shingo; Bannai, Makoto

    2015-02-15

    Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT. PMID:25516550

  14. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

    Directory of Open Access Journals (Sweden)

    Marie S A Palmnäs

    Full Text Available Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat or high fat (HF, 60% kcal fat and further into ad libitum water control (W or low-dose aspartame (A, 5-7 mg/kg/d in drinking water treatments for 8 week (n = 10-12 animals/treatment. Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05. Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.

  15. Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns

    OpenAIRE

    Campion, J.; Martinez, J. A.; Rodriguez-Sanchez, S. (Sonia); Soria, A. C.; Bañuelos, O. (Oscar); Olivares, M.; Milagro, F. I.; Garza, A.L. (Ana Laura) de la; Iglesia, R. (Rocío) de la; Boque, N. (Noemi)

    2013-01-01

    This study was conducted to determine the mechanisms implicated in the beneficial effects of apple polyphenols (APs) against diet-induced obesity in Wistar rats, described in a previous study from our group. Supplementation of high-fat sucrose diet with AP prevented adiposity increase by inhibition of adipocyte hypertrophy. Rats supplemented with AP exhibited improved glucose tolerance while adipocytes isolated from these rats showed an enhanced lipolytic response to isoproterenol. AP intake ...

  16. The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome

    OpenAIRE

    Steiner, Michel A.; Sciarretta, Carla; Pasquali, Anne; Jenck, Francois

    2013-01-01

    The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1) in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF) diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO) associated with metabolic syndrome (MetS...

  17. The Crude Extract from Puerariae Flower Exerts Antiobesity and Antifatty Liver Effects in High-Fat Diet-Induced Obese Mice

    OpenAIRE

    Masaki Aburada; Tsutomu Shimada; Kinya Takagaki; Motoya Ikeguchi; Rika Nagamine; Masahito Tsubata; Mayu Sameshima-Kamiya; Tomoyasu Kamiya

    2012-01-01

    Kudzu, a leguminous plant, has long been used in folk medicine. In particular, its flowers are used in Japanese and Chinese folk medicine for treating hangovers. We focused on the flower of Kudzu (Puerariae thomsonii), and we previously reported the antiobesity effect of Puerariae thomsonii flower extract (PFE) in humans. In this study, we conducted an animal study to investigate the effect of PFE on visceral fat and hepatic lipid levels in mice with diet-induced obesity. In addition, we focu...

  18. Anti-obesity effect of Triticum aestivum sprout extract in high-fat-diet-induced obese mice.

    Science.gov (United States)

    Im, Ji-Young; Ki, Hyeon-Hui; Xin, Mingjie; Kwon, Se-Uk; Kim, Young Ho; Kim, Dae-Ki; Hong, Sun-Pyo; Jin, Jong-Sik; Lee, Young-Mi

    2015-01-01

    Obesity is a common disease worldwide that often results in serious conditions including hypertension, diabetes, and hyperlipidemia. Many herbal medicines have been examined with regard to ameliorating obesity. We investigated the anti-obesity effects of 50% EtOH extract of Triticum aestivum sprout (TAEE) in high-fat-diet (HFD)-induced obese mice. TAEE administration (10, 50, or 200 mg/kg) for 6 weeks significantly decreased the body weights, serum total cholesterol (TC), and low-density lipoprotein cholesterol levels in HFD-fed mice. TAEE treatment reduced lipid accumulation in epididymal white adipose tissue (EWAT) and liver. Moreover, TC and lipid levels were decreased by TAEE treatment in liver. Serum leptin and adiponectin concentrations were reduced by TAEE treatment. TAEE-treated mice showed decreases in peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid synthase expression in EWAT. Furthermore, TAEE administration elevated levels of PPARα protein in the liver of HFD-induced obese mice. These results suggest that TAEE supplementation might be beneficial for the treatment and prevention of obesity and related diseases. PMID:25925980

  19. Decaffeinated green coffee bean extract attenuates diet-induced obesity and insulin resistance in mice.

    Science.gov (United States)

    Song, Su Jin; Choi, Sena; Park, Taesun

    2014-01-01

    This study investigated whether decaffeinated green coffee bean extract prevents obesity and improves insulin resistance and elucidated its mechanism of action. Male C57BL/6N mice (N = 48) were divided into six dietary groups: chow diet, HFD, HFD-supplemented with 0.1%, 0.3%, and 0.9% decaffeinated green coffee bean extract, and 0.15% 5-caffeoylquinic acid. Based on the reduction in HFD-induced body weight gain and increments in plasma lipids, glucose, and insulin levels, the minimum effective dose of green coffee bean extract appears to be 0.3%. Green coffee bean extract resulted in downregulation of genes involved in WNT10b- and galanin-mediated adipogenesis and TLR4-mediated proinflammatory pathway and stimulation of GLUT4 translocation to the plasma membrane in white adipose tissue. Taken together, decaffeinated green coffee bean extract appeared to reverse HFD-induced fat accumulation and insulin resistance by downregulating the genes involved in adipogenesis and inflammation in visceral adipose tissue. PMID:24817902

  20. Metabolic Effects of CX3CR1 Deficiency in Diet-Induced Obese Mice.

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    Rachana Shah

    Full Text Available The fractalkine (CX3CL1-CX3CR1 chemokine system is associated with obesity-related inflammation and type 2 diabetes, but data on effects of Cx3cr1 deficiency on metabolic pathways is contradictory. We examined male C57BL/6 Cx3cr1-/- mice on chow and high-fat diet to determine the metabolic effects of Cx3cr1 deficiency. We found no difference in body weight and fat content or feeding and energy expenditure between Cx3cr1-/- and WT mice. Cx3cr1-/- mice had reduced glucose intolerance assessed by intraperitoneal glucose tolerance tests at chow and high-fat fed states, though there was no difference in glucose-stimulated insulin values. Cx3cr1-/- mice also had improved insulin sensitivity at hyperinsulinemic-euglycemic clamp, with higher glucose infusion rate, rate of disposal, and hepatic glucose production suppression compared to WT mice. Enhanced insulin signaling in response to acute intravenous insulin injection was demonstrated in Cx3cr1-/- by increased liver protein levels of phosphorylated AKT and GSK3β proteins. There were no differences in adipose tissue macrophage populations, circulating inflammatory monocytes, adipokines, lipids, or inflammatory markers. In conclusion, we demonstrate a moderate and reproducible protective effect of Cx3cr1 deficiency on glucose intolerance and insulin resistance.

  1. 1H NMR-based metabolite profiling of diet-induced obesity in a mouse mode

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    Jee-youn Jung1,2,#, Il Yong Kim3,#, Yo Na Kim3,#, Jin-sup Kim1,5, Jae Hoon Shin3, Zi-hey Jang1,5, Ho-Sub Lee2, Geum-Sook Hwang1,5,* & Je Kyung Seong3,4,*

    2012-07-01

    Full Text Available High-fat diets (HFD and high-carbohydrate diets (HCD-induced obesity through different pathways, but the metabolicdifferences between these diets are not fully understood.Therefore, we applied proton nuclear magnetic resonance (1HNMR-based metabolomics to compare the metabolic patternsbetween C57BL/6 mice fed HCD and those fed HFD. Principalcomponent analysis derived from 1H NMR spectra of urineshowed a clear separation between the HCD and HFD groups.Based on the changes in urinary metabolites, the slow rate ofweight gain in mice fed the HCD related to activation of thetricarboxylic acid cycle (resulting in increased levels of citrateand succinate in HCD mice, while the HFD affected nicotinamidemetabolism (increased levels of 1-methylnicotineamide,nicotinamide-N-oxide in HFD mice, which leads to systemicoxidative stress. In addition, perturbation of gut microflorametabolism was also related to different metabolic patterns ofthose two diets. These findings demonstrate that 1H NMRbasedmetabolomics can identify diet-dependent perturbationsin biological pathways.

  2. IEX-1 deficiency induces browning of white adipose tissue and resists diet-induced obesity.

    Science.gov (United States)

    Shahid, Mohd; Javed, Ammar A; Chandra, David; Ramsey, Haley E; Shah, Dilip; Khan, Mohammed F; Zhao, Liping; Wu, Mei X

    2016-01-01

    Chronic inflammation plays a crucial role in the pathogenesis of obesity and insulin resistance. However, the primary mediators that affect energy homeostasis remain ill defined. Here, we report an unexpected role for immediate early response gene X-1 (IEX-1), a downstream target of NF-κB, in energy metabolism. We found that IEX-1 expression was highly induced in white adipose tissue (WAT) in both epidydmal and subcutaneous depots but not in interscapular brown adipose tissue (BAT) in mice fed a high fat diet (HFD). Null mutation of IEX-1 protected mice against HFD-induced adipose and hepatic inflammation, hepatic steatosis, and insulin resistance. Unexpectedly, IEX-1 knockout (IEX-1(-/-)) mice gained markedly less weight on HFD for 20 weeks as compared to wild-type (WT) littermates (37 ± 3 versus 48 ± 2 gm) due to increased energy expenditure. Mechanistically, we showed that IEX-1 deficiency induced browning and activated thermogenic genes program in WAT but not in BAT by promoting alternative activation of adipose macrophages. Consequently, IEX-1(-/-) mice exhibited enhanced thermogenesis (24 ± 0.1 versus 22 ± 0.1 kcal/hour/kg in WT mice) explaining increased energy expenditure and lean phenotype in these mice. In conclusion, the present study suggests that IEX-1 is a novel physiological regulator of energy homeostasis via its action in WAT. PMID:27063893

  3. Effects of Anthocyanin and Flavanol Compounds on Lipid Metabolism and Adipose Tissue Associated Systemic Inflammation in Diet-Induced Obesity.

    Science.gov (United States)

    van der Heijden, Roel A; Morrison, Martine C; Sheedfar, Fareeba; Mulder, Petra; Schreurs, Marijke; Hommelberg, Pascal P H; Hofker, Marten H; Schalkwijk, Casper; Kleemann, Robert; Tietge, Uwe J F; Koonen, Debby P Y; Heeringa, Peter

    2016-01-01

    Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential. Methods. Male C57BL/6J mice (n = 52) received a control low-fat diet (LFD; 10 kcal% fat) for 6 weeks followed by 24 weeks of either LFD (n = 13) or high-fat diet (HFD; 45 kcal% fat; n = 13) or HFD supplemented with 0.1% w/w of the flavanol compound epicatechin (HFD+E; n = 13) or an anthocyanin-rich bilberry extract (HFD+B; n = 13). Energy substrate utilization was determined by indirect calorimetry in a subset of mice following the dietary switch and at the end of the experiment. Blood samples were collected at baseline and at 3 days and 4, 12, and 20 weeks after dietary switch and analyzed for systemic lipids and proinflammatory cytokines. Adipose tissue (AT) histopathology and inflammatory gene expression as well as hepatic lipid content were analyzed after sacrifice. Results. The switch from a LFD to a HFD lowered the respiratory exchange ratio and increased plasma cholesterol and hepatic lipid content. These changes were not attenuated by HFD+E or HFD+B. Furthermore, the polyphenol compounds could not prevent HFD-induced systemic rise of TNF-α levels. Interestingly, a significant reduction in Tnf gene expression in HFD+B mice was observed in the AT. Furthermore, HFD+B, but not HFD+E, significantly prevented the early upregulation of circulating neutrophil chemoattractant mKC. However, no differences in AT histopathology were observed between the HFD types. Conclusion. Supplementation of HFD with an anthocyanin-rich bilberry extract but not with the flavanol epicatechin may exert beneficial effects on the systemic early inflammatory response associated with diet-induced obesity. These systemic effects were transient and

  4. Effects of Anthocyanin and Flavanol Compounds on Lipid Metabolism and Adipose Tissue Associated Systemic Inflammation in Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Roel A. van der Heijden

    2016-01-01

    Full Text Available Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential. Methods. Male C57BL/6J mice (n=52 received a control low-fat diet (LFD; 10 kcal% fat for 6 weeks followed by 24 weeks of either LFD (n=13 or high-fat diet (HFD; 45 kcal% fat; n=13 or HFD supplemented with 0.1% w/w of the flavanol compound epicatechin (HFD+E; n=13 or an anthocyanin-rich bilberry extract (HFD+B; n=13. Energy substrate utilization was determined by indirect calorimetry in a subset of mice following the dietary switch and at the end of the experiment. Blood samples were collected at baseline and at 3 days and 4, 12, and 20 weeks after dietary switch and analyzed for systemic lipids and proinflammatory cytokines. Adipose tissue (AT histopathology and inflammatory gene expression as well as hepatic lipid content were analyzed after sacrifice. Results. The switch from a LFD to a HFD lowered the respiratory exchange ratio and increased plasma cholesterol and hepatic lipid content. These changes were not attenuated by HFD+E or HFD+B. Furthermore, the polyphenol compounds could not prevent HFD-induced systemic rise of TNF-α levels. Interestingly, a significant reduction in Tnf gene expression in HFD+B mice was observed in the AT. Furthermore, HFD+B, but not HFD+E, significantly prevented the early upregulation of circulating neutrophil chemoattractant mKC. However, no differences in AT histopathology were observed between the HFD types. Conclusion. Supplementation of HFD with an anthocyanin-rich bilberry extract but not with the flavanol epicatechin may exert beneficial effects on the systemic early inflammatory response associated with diet-induced obesity. These systemic effects were transient

  5. Effect of Dietary Cocoa Tea (Camellia ptilophylla Supplementation on High-Fat Diet-Induced Obesity, Hepatic Steatosis, and Hyperlipidemia in Mice

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    Xiao Rong Yang

    2013-01-01

    Full Text Available Recent studies suggested that green tea has the potential to protect against diet-induced obesity. The presence of caffeine within green tea has caused limitations. Cocoa tea (Camellia ptilophylla is a naturally decaffeinated tea plant. To determine whether cocoa tea supplementation results in an improvement in high-fat diet-induced obesity, hyperlipidemia and hepatic steatosis, and whether such effects would be comparable to those of green tea extract, we studied six groups of C57BL/6 mice that were fed with (1 normal chow (N; (2 high-fat diet (21% butterfat + 0.15% cholesterol, wt/wt (HF; (3 a high-fat diet supplemented with 2% green tea extract (HFLG; (4 a high-fat diet supplemented with 4% green tea extract (HFHG; (5 a high-fat diet supplemented with 2% cocoa tea extract (HFLC; and (6 a high-fat diet supplemented with 4% cocoa tea extract (HFHC. From the results, 2% and 4% dietary cocoa tea supplementation caused a dose-dependent decrease in (a body weight, (b fat pad mass, (c liver weight, (d total liver lipid, (e liver triglyceride and cholesterol, and (f plasma lipids (triglyceride and cholesterol. These data indicate that dietary cocoa tea, being naturally decaffeinated, has a beneficial effect on high-fat diet-induced obesity, hepatomegaly, hepatic steatosis, and elevated plasma lipid levels in mice, which are comparable to green tea. The present findings have provided the proof of concept that dietary cocoa tea might be of therapeutic value and could therefore provide a safer and cost effective option for patients with diet-induced metabolic syndrome.

  6. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Jensen, Majbrit M; Overgaard, Agnete;

    2013-01-01

    clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity. This is interesting, as obese patients have reduced central...... dopaminergic activity thought to provide a drive for compensatory overeating, but whether treatment with an uptake inhibitor counteracts these changes or not has not been investigated. Tesofensine treatment (2.0mg/kg/day for 14days) caused a pronounced anorexigenic and weight-reducing response in DIO rats as...

  7. Calorie restriction and endurance exercise share potent anti-inflammatory function in adipose tissues in ameliorating diet-induced obesity and insulin resistance in mice

    OpenAIRE

    Yan Zhen; Li Wenjun; Mao Ting; You Jia; Zhao Feng; Qi Qibin; Shao Mengle; Li Shoufeng; Huang Ping; Liu Yong

    2010-01-01

    Abstract Background Calorie restriction (CR) and endurance exercise are known to attenuate obesity and improve the metabolic syndrome. The aim of this study was to directly compare the effects of CR and endurance exercise in a mouse model of diet-induced obesity and insulin resistance. Methods Adult male C57BL/6N mice were randomly assigned and subjected to one of the six interventions for 8 weeks: low-fat diet (LC, 10% fat), low-fat diet with 30% calorie restriction (LR), high-fat diet (HC, ...

  8. Dopamine transporter and D2 receptor binding densities in mice prone or resistant to chronic high fat diet-induced obesity.

    Science.gov (United States)

    Huang, Xu-Feng; Zavitsanou, Katerina; Huang, Xin; Yu, Yinghua; Wang, HongQin; Chen, Feng; Lawrence, Andrew J; Deng, Chao

    2006-12-15

    This study examined the density of dopamine transporter (DAT) and D2 receptors in the brains of chronic high-fat diet-induced obese (cDIO), obese-resistant (cDR) and low-fat-fed (LF) control mice. Significantly decreased DAT densities were observed in cDR mice compared to cDIO and LF mice, primarily in the nucleus accumbens, striatal and hypothalamic regions. D2 receptor density was significantly lower in the rostral part of caudate putamen in cDIO mice compared to cDR and LF mice. PMID:17000016

  9. Anti-Obesity Effects of Aster spathulifolius Extract in High-Fat Diet-Induced Obese Rats.

    Science.gov (United States)

    Kim, Sa-Jic; Bang, Chae-Young; Guo, Yuan-Ri; Choung, Se-Young

    2016-04-01

    The aim of this study was to investigate the anti-obesity and antihyperlipidemic efficacy and molecular mechanisms of Aster spathulifolius Maxim extract (ASE) in rats with high-fat diet (HFD)-induced obesity. Rats were separately fed a normal diet or a HFD for 8 weeks, then they were treated with ASE (62.5, 125, or 250 mg/kg) for another 4.5 weeks. The ASE supplementation significantly lowered body weight gain, visceral fat pad weights, serum lipid levels, as well as hepatic lipid levels in HFD-induced obese rats. Histological analysis showed that the ASE-treated group showed lowered numbers of lipid droplets and smaller size of adipocytes compared to the HFD group. To understand the mechanism of action of ASE, the expression of genes and proteins involved in obesity were measured in liver and skeletal muscle. The expression of fatty acid oxidation and thermogenesis-related genes (e.g., PPAR-α, ACO, CPT1, UCP2, and UCP3) of HFD-induced obese rats were increased by ASE treatment. On the other hand, ASE treatment resulted in decreased expression of fat intake-related gene ACC2 and lipogenesis-related genes (e.g., SREBP-1c, ACC1, FAS, SCD1, GPATR, AGPAT, and DGAT). Furthermore, ASE treatment increased the level of phosphorylated AMPKα in obese rats. Similarly, the level of phosphorylated ACC, a target protein of AMPKα in ASE groups, was increased by ASE treatment compared with the HFD group. These results suggest that ASE attenuated visceral fat accumulation and improved hyperlipidemia in HFD-induced obese rats by increasing lipid metabolism through the regulation of AMPK activity and the expression of genes and proteins involved in lipolysis and lipogenesis. PMID:26908215

  10. Ginger extract prevents high-fat diet-induced obesity in mice via activation of the peroxisome proliferator-activated receptor δ pathway.

    Science.gov (United States)

    Misawa, Koichi; Hashizume, Kojiro; Yamamoto, Masaki; Minegishi, Yoshihiko; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    The initiation of obesity entails an imbalance wherein energy intake exceeds expenditure. Obesity is increasing in prevalence and is now a worldwide health problem. Food-derived peroxisome proliferator-activated receptor δ (PPARδ) stimulators represent potential treatment options for obesity. Ginger (Zingiber officinale Roscoe) was previously shown to regulate the PPARγ signaling pathway in adipocytes. In this study, we investigated the antiobesity effects of ginger in vivo and the mechanism of action in vitro. Energy expenditure was increased, and diet-induced obesity was attenuated in C57BL/6J mice treated with dietary ginger extract (GE). GE also increased the number of Type I muscle fibers, improved running endurance capacity and upregulated PPARδ-targeted gene expression in skeletal muscle and the liver. 6-Shogaol and 6-gingerol acted as specific PPARδ ligands and stimulated PPARδ-dependent gene expression in cultured human skeletal muscle myotubes. An analysis of cellular respiration revealed that pretreating cultured skeletal muscle myotubes with GE increased palmitate-induced oxygen consumption rate, which suggested an increase in cellular fatty acid catabolism. These results demonstrated that sustained activation of the PPARδ pathway with GE attenuated diet-induced obesity and improved exercise endurance capacity by increasing skeletal muscle fat catabolism. 6-Shogaol and 6-gingerol may be responsible for the regulatory effects of dietary ginger on PPARδ signaling. PMID:26101135

  11. Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice.

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    Frida Fåk

    Full Text Available OBJECTIVE: To investigate whether the specific strains of Lactobacillus reuteri modulates the metabolic syndrome in Apoe-/- mice. METHODS: 8 week-old Apoe-/- mice were subdivided into four groups who received either L. reuteri ATCC PTA 4659 (ATCC, DSM 17938 (DSM, L6798, or no bacterial supplement in the drinking water for 12 weeks. The mice were fed a high-fat Western diet with 0.2% cholesterol and body weights were monitored weekly. At the end of the study, oral glucose and insulin tolerance tests were conducted. In addition, adipose and liver weights were recorded along with analyses of mRNA expression of ileal Angiopoietin-like protein 4 (Angptl4, the macrophage marker F4/80 encoded by the gene Emr1 and liver Acetyl-CoA carboxylase 1 (Acc1, Fatty acid synthase (Fas and Carnitine palmitoyltransferase 1a (Cpt1a. Atherosclerosis was assessed in the aortic root region of the heart. RESULTS AND CONCLUSIONS: Mice receiving L. reuteri ATCC gained significantly less body weight than the control mice, whereas the L6798 mice gained significantly more. Adipose and liver weights were also reduced in the ATCC group. Serum insulin levels were lower in the ATCC group, but no significant effects were observed in the glucose or insulin tolerance tests. Lipogenic genes in the liver were not altered by any of the bacterial treatments, however, increased expression of Cpt1a was found in the ATCC group, indicating increased β-oxidation. Correspondingly, the liver trended towards having lower fat content. There were no effects on inflammatory markers, blood cholesterol or atherosclerosis. In conclusion, the probiotic L. reuteri strain ATCC PTA 4659 partly prevented diet-induced obesity, possibly via a previously unknown mechanism of inducing liver expression of Cpt1a.

  12. Short-chain fructo-oligosaccharides modulate intestinal microbiota and metabolic parameters of humanized gnotobiotic diet induced obesity mice.

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    Frederique Respondek

    Full Text Available Prebiotic fibres like short-chain fructo-oligosaccharides (scFOS are known to selectively modulate the composition of the intestinal microbiota and especially to stimulate Bifidobacteria. In parallel, the involvement of intestinal microbiota in host metabolic regulation has been recently highlighted. The objective of the study was to evaluate the effect of scFOS on the composition of the faecal microbiota and on metabolic parameters in an animal model of diet-induced obesity harbouring a human-type microbiota. Forty eight axenic C57BL/6J mice were inoculated with a sample of faecal human microbiota and randomly assigned to one of 3 diets for 7 weeks: a control diet, a high fat diet (HF, 60% of energy derived from fat or an isocaloric HF diet containing 10% of scFOS (HF-scFOS. Mice fed with the two HF gained at least 21% more weight than mice from the control group. Addition of scFOS partially abolished the deposition of fat mass but significantly increased the weight of the caecum. The analysis of the taxonomic composition of the faecal microbiota by FISH technique revealed that the addition of scFOS induced a significant increase of faecal Bifidobacteria and the Clostridium coccoides group whereas it decreased the Clostridium leptum group. In addition to modifying the composition of the faecal microbiota, scFOS most prominently affected the faecal metabolome (e.g. bile acids derivatives, hydroxyl monoenoic fatty acids as well as urine, plasma hydrophilic and plasma lipid metabolomes. The increase in C. coccoides and the decrease in C. leptum, were highly correlated to these metabolic changes, including insulinaemia, as well as to the weight of the caecum (empty and full but not the increase in Bifidobacteria. In conclusion scFOS induce profound metabolic changes by modulating the composition and the activity of the intestinal microbiota, that may partly explain their effect on the reduction of insulinaemia.

  13. Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption123

    Science.gov (United States)

    Land, Benjamin B.; Wickham, Robert J.; Maldonado-Aviles, Jaime; de Araujo, Ivan E.; Addy, Nii A.

    2016-01-01

    Abstract The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol. PMID:27257625

  14. Black tea polyphenols and polysaccharides improve body composition, increase fecal fatty acid, and regulate fat metabolism in high-fat diet-induced obese rats.

    Science.gov (United States)

    Wu, Tao; Guo, Yu; Liu, Rui; Wang, Kuan; Zhang, Min

    2016-05-18

    With the current changes in diet and living habits, obesity has become a global health problem. Thus, the weight-reducing function of tea has attracted considerable attention. This study investigated the anti-obesity effect and the mechanism of black tea (BT) polyphenols and polysaccharides in male Sprague-Dawley rats. The BT polyphenols and polysaccharides reduced the body weight, Lee's index, visceral fat weight, and fat cell size but improved the biochemical profile and increased the fecal fatty acid content, thereby preventing high-fat diet-induced obesity. A gene expression profile array was used to screen eight upregulated and five downregulated differentially expressed genes that affect fat metabolic pathways, such as glycerolipid and glycerophospholipid metabolism, fatty acid degradation, glycolysis and gluconeogenesis, bile and pancreatic secretion, the insulin signaling pathway, and steroid hormone secretion. The BT polyphenols and polysaccharides suppressed the formation and accumulation of fat and promoted its decomposition to prevent obesity. PMID:27161951

  15. Undaria pinnatifida and Fucoxanthin Ameliorate Lipogenesis and Markers of Both Inflammation and Cardiovascular Dysfunction in an Animal Model of Diet-Induced Obesity

    Science.gov (United States)

    Grasa-López, Ameyalli; Miliar-García, Ángel; Quevedo-Corona, Lucía; Paniagua-Castro, Norma; Escalona-Cardoso, Gerardo; Reyes-Maldonado, Elba; Jaramillo-Flores, María-Eugenia

    2016-01-01

    Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related. PMID:27527189

  16. Undaria pinnatifida and Fucoxanthin Ameliorate Lipogenesis and Markers of Both Inflammation and Cardiovascular Dysfunction in an Animal Model of Diet-Induced Obesity.

    Science.gov (United States)

    Grasa-López, Ameyalli; Miliar-García, Ángel; Quevedo-Corona, Lucía; Paniagua-Castro, Norma; Escalona-Cardoso, Gerardo; Reyes-Maldonado, Elba; Jaramillo-Flores, María-Eugenia

    2016-01-01

    Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related. PMID:27527189

  17. Decrease in myostatin by ladder-climbing training is associated with insulin resistance in diet-induced obese rats

    Institute of Scientific and Technical Information of China (English)

    Tang Liang; Luo Kai; Liu Chentao; Wang Xudan; Zhang Didi; Chi Aiping; Zhang Jing

    2014-01-01

    Background Suppression of myostatin (MSTN) has been associated with skeletal muscle atrophy and insulin resistance (IR).However,few studies link MSTN suppression by ladder-climbing training (LCT) and IR.Therefore,we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR.Methods The rats were randomly assigned to two types of diet:normal pellet diet (NPD,n=8) and high-fat diet (HFD,n=16).After 8 weeks,the HFD rats were randomly re-assigned to two groups (n=8 for each group):HFD sedentary (HFD-S) and high-fat diet ladder-climbing training (HFD-LCT).HFD-LCT rats were assigned to LCT for 8 weeks.Western blotting,immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN,GLUT4,PI3K,Akt and Akt-activated targets (mTOR,FoxO1 and GSK-3β).Results The LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats.MSTN protein levels decreased in matching serum (42%,P=0.007) and muscle samples (25%,P=0.035) and its receptor mRNA expression also decreased (16%,P=0.041) from obese rats after LCT.But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups (P=0.074).The ladder-climbing training significantly enhanced PI3K activity (1.7-fold,P=0.024) and Akt phosphorylation (83.3%,P=0.022) in HFD-fed rats,significantly increased GLUT4 protein expression (84.5%,P=-0.036),enhanced phosphorylation of mTOR (4.8-fold,P <0.001) and inhibited phosphorylation of FoxO1 (57.7%,P=0.020),but did not affect the phosphorylation of GSK-3β.Conclusions The LCT significantly reduced IR in diet-induced obese rats.MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.

  18. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    Science.gov (United States)

    Litwak, Sara A; Loh, Kim; Stanley, William J; Pappas, Evan G; Wali, Jibran A; Selck, Claudia; Strasser, Andreas; Thomas, Helen E; Gurzov, Esteban N

    2016-01-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity. PMID:27033313

  19. The anti-obesity effects of Lactobacillus casei strain Shirota versus Orlistat on high fat diet-induced obese rats

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    Golgis Karimi

    2015-12-01

    Full Text Available Background: Obesity and overweight are major public health problems. Various factors, such as daily nutritional habits, physical inactivity, and genetic, are related to the prevalence of obesity. Recently, it was revealed that the gut microflora may also play an important role in weight management. Thus, this study aimed to determine the anti-obesity effects of Lactobacillus casei strain Shirota (LcS compared with those of orlistat in an animal model fed a high-fat diet (HFD. Design: Thirty-two male Sprague-Dawley rats were assigned to four groups fed various diets as follows: a standard diet group, HFD group, HFD supplemented with LcS (108109 colony-forming units (HFD-LcS group, and HFD group treated with Orlistat (10 mg/kg body weight. After 15 weeks, the weights of organs, body weight, body fat mass and serological biomarkers were measured. In addition, histological analysis of the liver and adipose tissue was performed. Results: Body weight, body mass index, fat mass, leptin and glucose levels were lower, and high-density lipoprotein and adiponectin levels were higher in the HFD-LcS and HFD-orlistat groups than in the HFD group. In addition a significant difference in body fat mass was observed between HFD-LcS group with HFD-orlistat group (19.19±5.76 g vs. 30.19±7.98 g. Although the interleukin-6 level was significantly decreased in the HFD-LcS and HFD-orlistat groups compared with the HFD group, no significant change was observed in other inflammatory biomarkers. Conclusion: The results of the present study show that LcS supplementation improves body weight management and the levels of some related biomarkers. In addition, LcS supplementation showed a better result in fat mass and alanine aminotransferase reduction than Orlistat. Further studies are needed to elucidate the anti-obesity effects of LcS, with a longer period of supplementation.

  20. Apple-Derived Pectin Modulates Gut Microbiota, Improves Gut Barrier Function, and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity

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    Tingting Jiang

    2016-02-01

    Full Text Available This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8 or a high-fat diet (HFD; n = 32 for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8 or pectin-supplemented HFD (HF-P group; n = 8 for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p < 0.01 and serum total cholesterol level (1.46 ± 0.13 mmol/L vs. 2.06 ± 0.26 mmol/L, p < 0.01. Compared to the Chow group, the HF group showed a decrease in Bacteroidetes phylum and an increase in Firmicutes phylum, as well as subordinate categories (p < 0.01. These changes were restored to the normal levels in the HF-P group. Furthermore, compared to the HF group, the HF-P group displayed improved intestinal alkaline phosphatase (0.57 ± 0.20 vs. 0.30 ± 0.19, p < 0.05 and claudin 1 (0.76 ± 0.14 vs. 0.55 ± 0.18, p < 0.05 expression, and decreased Toll-like receptor 4 expression in ileal tissue (0.76 ± 0.58 vs. 2.04 ± 0.89, p < 0.01. The HF-P group also showed decreased inflammation (TNFα: 316.13 ± 7.62 EU/mL vs. 355.59 ± 8.10 EU/mL, p < 0.01; IL-6: 51.78 ± 2.35 EU/mL vs. 58.98 ± 2.59 EU/mL, p < 0.01 and metabolic endotoxemia (2.83 ± 0.42 EU/mL vs. 0.68 ± 0.14 EU/mL, p < 0.01. These results suggest that apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats.

  1. Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity

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    Kwon Eun-Young

    2012-09-01

    Full Text Available Abstract Background Visceral white adipose tissue (WAT hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity. Results C57BL/6 J mice were fed a high-fat diet (HFD or normal diet (ND and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery after 2–4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9 and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14. Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages. Conclusions In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches

  2. The obesity and fatty liver are reduced by plant-derived Pediococcus pentosaceus LP28 in high fat diet-induced obese mice.

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    Xingrong Zhao

    Full Text Available We evaluated the effect of an oral administration of a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28, on metabolic syndrome by using high fat diet-induced obese mice. The obese mice were divided into 2 groups and fed either a high fat or regular diet for 8 weeks. Each group was further divided into 3 groups, which took LP28, another plant-derived Lactobacillus plantarum SN13T (SN13T or no lactic acid bacteria (LAB. The lean control mice were fed a regular diet without inducing obesity prior to the experiment. LP28 reduced body weight gain and liver lipid contents (triglyceride and cholesterol, in mice fed a high fat diet for 8 weeks (40%, 54%, and 70% less than those of the control group without LAB, and P = 0.018, P<0.001, and P = 0.021, respectively, whereas SN13T and the heat treated LP28 at 121°C for 15 min were ineffective. Abdominal visceral fat in the high fat diet mice fed with LP28 was also lower than that without LAB by 44%, although it was not significant but borderline (P = 0.076. The sizes of the adipocytes and the lipid droplets in the livers were obviously decreased. A real-time PCR analyses showed that lipid metabolism-related genes, such as CD36 (P = 0.013, SCD1 encoding stearoyl-CoA desaturase 1 (not significant but borderline, P = 0.066, and PPARγ encoding peroxisome proliferator-activated receptor gamma (P = 0.039, were down-regulated by taking LP28 continuously, when compared with those of the control group. In conclusion, LP28 may be a useful LAB strain for the prevention and reduction of the metabolic syndrome.

  3. Peroxisome proliferator-activated receptors-alpha and gamma are targets to treat offspring from maternal diet-induced obesity in mice.

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    D'Angelo Carlo Magliano

    Full Text Available AIM: The aim of the present study was to evaluate whether activation of peroxisome proliferator-activated receptor (PPARalpha and PPARgamma by Bezafibrate (BZ could attenuate hepatic and white adipose tissue (WAT abnormalities in male offspring from diet-induced obese dams. MATERIALS AND METHODS: C57BL/6 female mice were fed a standard chow (SC; 10% lipids diet or a high-fat (HF; 49% lipids diet for 8 weeks before mating and during gestation and lactation periods. Male offspring received SC diet at weaning and were subdivided into four groups: SC, SC/BZ, HF and HF/BZ. Treatment with BZ (100 mg/Kg diet started at 12 weeks of age and was maintained for three weeks. RESULTS: The HF diet resulted in an overweight phenotype and an increase in oral glucose intolerance and fasting glucose of dams. The HF offspring showed increased body mass, higher levels of plasmatic and hepatic triglycerides, higher levels of pro-inflammatory and lower levels of anti-inflammatory adipokines, impairment of glucose metabolism, abnormal fat pad mass distribution, higher number of larger adipocytes, hepatic steatosis, higher expression of lipogenic proteins concomitant to decreased expression of PPARalpha and carnitine palmitoyltransferase I (CPT-1 in liver, and diminished expression of PPARgamma and adiponectin in WAT. Treatment with BZ ameliorated the hepatic and WAT abnormalities generated by diet-induced maternal obesity, with improvements observed in the structural, biochemical and molecular characteristics of the animals' livers and epididymal fat. CONCLUSION: Diet-induced maternal obesity lead to alterations in metabolism, hepatic lipotoxicity and adverse liver and WAT remodeling in the offspring. Targeting PPAR with Bezafibrate has beneficial effects reducing the alterations, mainly through reduction of WAT inflammatory state through PPARgamma activation and enhanced hepatic beta-oxidation due to increased PPARalpha/PPARgamma ratio in liver.

  4. Cinnamomum camphora Seed Kernel Oil Improves Lipid Metabolism and Enhances β3-Adrenergic Receptor Expression in Diet-Induced Obese Rats.

    Science.gov (United States)

    Fu, Jing; Zeng, Cheng; Zeng, Zheling; Wang, Baogui; Wen, Xuefang; Yu, Ping; Gong, Deming

    2016-06-01

    The effects of dietary Cinnamomum camphora seed kernel oil (CCSKO) containing medium-chain triacylglycerols on lipid metabolism and mRNA and protein expression of β-3 adrenergic receptor in adipose tissue were studied in diet-induced obese rats. High fat food-induced obese rats were randomly divided into CCSKO group, Lard group, Soybean oil (SOY) group and naturally restoring group (n = 10). Rats fed with low fat food were used as a normal control group. Significant decreases in body mass and abdominal fat mass/body mass after 12 weeks were found in CCSKO group as compared with Lard and SOY groups (p < 0.05). Levels of blood total cholesterol (TC), triglyceride, free fatty acid, fasting insulin and insulin resistance in the CCSKO group were decreased significantly, and noradrenaline level and insulin sensitivity index in the CCSKO group were significantly higher than other groups. Meanwhile liver TC and triglyceride levels in the CCSKO group were also decreased markedly. Expression levels of β3-adrenergic receptor mRNA and protein were higher in CCSKO group than in Lard and SOY groups. These results suggest that CCSKO may contribute to reduction of the body fat mass, promote lipid metabolism and up-regulate β3-adrenergic receptor expression in high fat diet-induced obese rats. PMID:27068065

  5. Chrysobalanus icaco L. Leaves Normalizes Insulin Sensitivity and Blood Glucose and Inhibits Weight Gain in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    White, Pollyanna A S; Araújo, Jessica M D; Cercato, Luana M; Souza, Lucas A; Barbosa, Ana Paula Oliveira; Quintans-Junior, Lucindo José; Machado, Ubiratan F; Camargo, Enilton A; Brito, Luciana C; Santos, Marcio Roberto V

    2016-02-01

    Chrysobalanus icaco L. is a medicinal plant present in the Brazilian coastline and known for its hypoglicemic and antioxidant properties. Here, we assessed the beneficial metabolic effects of the aqueous extract of C. icaco (AECI) leaves in diet-induced obese mice. Swiss mice were fed standard chow (SC used as controls) or high-fat diet (HFD) to induce obesity. After 10 weeks, mice on each diet were divided into two groups with one group used as control while the other group treated with AECI for 4 weeks resulting in four groups of mice: SC; SC treated with AECI (SC + AECI); HFD; and HFD treated with AECI (HFD + AECI). AECI was administered drinking water at about 200 mg/kg. AECI was able to normalize insulin (13,682 ± 1090 vs. 9828 ± 485 AU, P < .05) and fasting blood glucose (192.8 ± 14.2 vs. 132.3 ± 6.4 mg/dL, P < .05) and inhibit weight gain (39 ± 5.7%) and fat storage in liver (72.60 ± 3.83%, P < .0001), despite the high-fat intake. These findings reinforce the use of AECI in hyperglycemia and highlight the potential extract's effect in preventing weight gain and fat accumulation in liver of diet-induced obese mice. PMID:26854845

  6. Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription

    OpenAIRE

    Fang, Cindy X.; Dong, Feng; Thomas, D. Paul; Ma, Heng; He, Leilei; Ren, Jun

    2008-01-01

    Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed to evaluate the role of Akt, the forkhead transcription factor Foxo3a, and atrophy genes muscle-specific RING finger (MuRF)-1 and atrogin-1 in cardiac hypertrophy and contractile dysfunction associated with high-fat diet-induced obesity. Mice were fed a low- or high-fat diet for 6 mo along ...

  7. Effects of treadmill exercise on skeletal muscle mTOR signaling pathway in high-fat diet-induced obese mice

    OpenAIRE

    Woo, Jin Hee; Shin, Ki Ok; Lee, Yul Hyo; Jang, Ki Soeng; Bae, Ju Yong; Roh, Hee Tae

    2016-01-01

    [Purpose] The aim of this study was to investigate the effects of regular treadmill exercise on skeletal muscle Rictor-Akt and mTOR-Raptor-S6K1 signaling pathway in high-fat diet-induced obese mice. [Subjects and Methods] Four- week-old C57BL/6 mice were adopted and classified into normal diet group (ND, n = 10), normal diet and training group (NDT, n = 10), high-fat diet group (HF, n = 10), and high-fat diet and training group (HFT, n = 10). The exercise program consisted of a treadmill exer...

  8. Direct infusion MS-based lipid profiling reveals the pharmacological effects of compound K-reinforced ginsenosides in high-fat diet induced obese mice.

    Science.gov (United States)

    Shon, Jong Cheol; Shin, Hwa-Soo; Seo, Yong Ki; Yoon, Young-Ran; Shin, Heungsop; Liu, Kwang-Hyeon

    2015-03-25

    The serum lipid metabolites of lean and obese mice fed normal or high-fat diets were analyzed via direct infusion nanoelectrospray-ion trap mass spectrometry followed by multivariate analysis. In addition, lipidomic biomarkers responsible for the pharmacological effects of compound K-reinforced ginsenosides (CK), thus the CK fraction, were evaluated in mice fed high-fat diets. The obese and lean groups were clearly discriminated upon principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) score plot, and the major metabolites contributing to such discrimination were triglycerides (TGs), cholesteryl esters (CEs), phosphatidylcholines (PCs), and lysophosphatidylcholines (LPCs). TGs with high total carbon number (>50) and low total carbon number (fat diet induced obesity in mice, respectively. When the CK fraction was fed to obese mice that consumed a high-fat diet, the levels of certain lipids including LPCs and CEs became similar to those of mice fed a normal diet. Such metabolic markers can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, changes in the levels of such metabolites can be employed to assess the risk of obesity and the therapeutic effects of obesity management. PMID:25744175

  9. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-sucrose diet-induced obese mice.

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    Ji-Hee Kang

    Full Text Available Previously, we reported that Lactobacillus gasseri BNR17 (BNR17, a probiotic strain isolated from human breast milk, inhibited increases in body weight and adipocyte tissue weight in high-sucrose diet-fed Sprague-Dawley (SD rats and reduced glucose levels in type 2 diabetes mice. In the current study, we conducted further experiments to extend these observations and elucidate the mechanism involved. C57BL/6J mice received a normal diet, high-sucrose diet or high-sucrose diet containing L. gasseri BNR17 (10(9 or 10(10 CFU for 10 weeks. The administration of L. gasseri BNR17 significantly reduced the body weight and white adipose tissue weight regardless of the dose administered. In BNR17-fed groups, mRNA levels of fatty acid oxidation-related genes (ACO, CPT1, PPARα, PPARδ were significantly higher and those of fatty acid synthesis-related genes (SREBP-1c, ACC were lower compared to the high-sucrose-diet group. The expression of GLUT4, main glucose transporter-4, was elevated in BNR17-fed groups. L. gasseri BNR17 also reduced the levels of leptin and insulin in serum. These results suggest that the anti-obesity actions of L. gasseri BNR17 can be attributed to elevated expression of fatty acid oxidation-related genes and reduced levels of leptin. Additionally, data suggested the anti-diabetes activity of L. gasseri BNR17 may be to due elevated GLUT4 and reduced insulin levels.

  10. Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice.

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    Min He

    Full Text Available BACKGROUND: Glucagon-like peptide-1 (GLP-1 is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a non-peptidic GLP-1 receptor (GLP-1R agonist. While its oral bioavailability still poses significant challenges, Boc5, one of the first such compounds, has demonstrated the attainment of GLP-1R agonism in diabetic mice. The present work was to investigate whether subchronic Boc5 treatment can restore glycemic control and induce sustainable weight loss in diet-induced obese (DIO mice, an animal model of human obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: DIO mice were treated three times a week with Boc5 (0.3, 1 and 3 mg for 12 weeks. Body weight, body mass index (BMI, food intake, fasting glucose, intraperitoneal glucose tolerance and insulin induced glucose clearance were monitored regularly throughout the treatment. Glucose-stimulated insulin secretion, β-cell mass, islet size, body composition, serum metabolic profiles, lipogenesis, lipolysis, adipose hypertrophy and lipid deposition in the liver and muscle were also measured after 12 weeks of dosing. Boc5 dose-dependently reduced body weight, BMI and food intake in DIO mice. These changes were associated with significant decreases in fat mass, adipocyte hypertrophy and peripheral tissue lipid accumulation. Boc5 treatment also restored glycemic control through marked improvement of insulin sensitivity and normalization of β-cell mass. Administration of Boc5 (3 mg reduced basal but enhanced insulin-mediated glucose incorporation and noradrenaline-stimulated lipolysis in isolated adipocytes from obese mice. Furthermore, circulating leptin, adiponectin, triglyceride, total cholesterol, nonesterified fatty acid and high-density lipoprotein/low-density lipoprotein ratio were normalized to various

  11. Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier.

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    Yong Fan

    Full Text Available Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB integrity may be one of the crucial underlying factors accounting for this change.

  12. Combined Ethanol Extract of Grape Pomace and Omija Fruit Ameliorates Adipogenesis, Hepatic Steatosis, and Inflammation in Diet-Induced Obese Mice

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    Su-Jung Cho

    2013-01-01

    Full Text Available The aim of this study was to evaluate the long-term effects of grape pomace ethanol extract (GPE with or without omija fruit ethanol extract (OFE on adiposity, hepatic steatosis, and inflammation in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (HFD as the control diet and HFD plus GPE (0.5%, w/w with or without OFE (0.05%, w/w as the experimental diet for 12 weeks. GPE alone did not significantly affect adipogenesis and hepatic steatosis. However, the supplementation of GPE + OFE significantly lowered body weight gain, white adipose tissue weight, adipocyte size, and plasma free fatty acid and adipokines (leptin, PAI-1, IL-6, and MCP-1 levels in HFD-fed mice compared to those of the control group. These beneficial effects of GPE + OFE were partly related to the decreased expression of lipogenic and inflammatory genes in white adipose tissue. GPE + OFE supplementation also significantly lowered liver weight and ameliorated fatty liver by inhibiting expression of hepatic genes involved in fatty acid and cholesterol syntheses as well as inflammation and by activating hepatic fatty acid oxidation. These findings suggest that the combined ethanol extract of grape pomace and omija fruit has the potential to improve adiposity and fatty liver in diet-induced obese mice.

  13. Study on Diet-induced Obesity Resistance Phenomenon and Its Mechanism%肥胖抵抗现象及其机制研究

    Institute of Scientific and Technical Information of China (English)

    刘春阳; 黄徐根

    2014-01-01

    随着肥胖症在全球迅速蔓延,国内外学者对肥胖的研究也逐渐深入,食源性肥胖抵抗(diet-induced obesity resistance,DIO-R)表现为肥胖易感程度低,与肥胖机体相比能量代谢状况较好,是机体能量代谢研究中较新的研究方向.本研究探讨了现阶段国内外肥胖抵抗大鼠的主要筛选方法,就食源性肥胖抵抗与食源性肥胖(diet-induced obesity,DIO)机体代谢差异最新研究成果进行综述,从瘦素敏感性、胰岛素敏感性、脂联素水平、食物利用率等方面分析了肥胖抵抗现象的发生机制,并从运动生理生化的角度提出现阶段肥胖抵抗研究存在的问题,对肥胖抵抗大鼠代谢及机制差异的研究前景进行展望.

  14. Mice deficient in the respiratory chain gene Cox6a2 are protected against high-fat diet-induced obesity and insulin resistance.

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    Roel Quintens

    Full Text Available Oxidative phosphorylation in mitochondria is responsible for 90% of ATP synthesis in most cells. This essential housekeeping function is mediated by nuclear and mitochondrial genes encoding subunits of complex I to V of the respiratory chain. Although complex IV is the best studied of these complexes, the exact function of the striated muscle-specific subunit COX6A2 is still poorly understood. In this study, we show that Cox6a2-deficient mice are protected against high-fat diet-induced obesity, insulin resistance and glucose intolerance. This phenotype results from elevated energy expenditure and a skeletal muscle fiber type switch towards more oxidative fibers. At the molecular level we observe increased formation of reactive oxygen species, constitutive activation of AMP-activated protein kinase, and enhanced expression of uncoupling proteins. Our data indicate that COX6A2 is a regulator of respiratory uncoupling in muscle and we demonstrate that a novel and direct link exists between muscle respiratory chain activity and diet-induced obesity/insulin resistance.

  15. Early Onset Inflammation in Pre-Insulin-Resistant Diet-Induced Obese Rats Does Not Affect the Vasoreactivity of Isolated Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Raun, Kirsten; Boonen, Harrie C M;

    2012-01-01

    myography, we tested the vascular function of isolated small mesenteric arteries. Results: DIO animals had significantly (p <0.05) increased body weight (721.2 ± 6.3 g) compared to age- and sex-matched controls (643.4 ± 14.6 g), as well as a significant increase (p <0.01) in body fat percentage (29.7 ± 1....... Our study aimed to investigate signs of inflammation and their relation to vascular dysfunction in rats receiving a high fat diet. Methods: Diet-induced obese (DIO) rats were used as a model since these rats exhibit a human pre-diabetic pathology. Oral glucose and insulin tolerance tests were......Background: Obesity is an increasing burden affecting developed and emerging societies since it is associated with an increased risk of diabetes and consequent cardiovascular complications. Increasing evidence points towards a pivotal role of inflammation in the etiology of vascular dysfunction...

  16. Integrin-Linked Kinase in Muscle Is Necessary for the Development of Insulin Resistance in Diet-Induced Obese Mice.

    Science.gov (United States)

    Kang, Li; Mokshagundam, Shilpa; Reuter, Bradley; Lark, Daniel S; Sneddon, Claire C; Hennayake, Chandani; Williams, Ashley S; Bracy, Deanna P; James, Freyja D; Pozzi, Ambra; Zent, Roy; Wasserman, David H

    2016-06-01

    Diet-induced muscle insulin resistance is associated with expansion of extracellular matrix (ECM) components, such as collagens, and the expression of collagen-binding integrin, α2β1. Integrins transduce signals from ECM via their cytoplasmic domains, which bind to intracellular integrin-binding proteins. The integrin-linked kinase (ILK)-PINCH-parvin (IPP) complex interacts with the cytoplasmic domain of β-integrin subunits and is critical for integrin signaling. In this study we defined the role of ILK, a key component of the IPP complex, in diet-induced muscle insulin resistance. Wild-type (ILK(lox/lox)) and muscle-specific ILK-deficient (ILK(lox/lox)HSAcre) mice were fed chow or a high-fat (HF) diet for 16 weeks. Body weight was not different between ILK(lox/lox) and ILK(lox/lox)HSAcre mice. However, HF-fed ILK(lox/lox)HSAcre mice had improved muscle insulin sensitivity relative to HF-fed ILK(lox/lox) mice, as shown by increased rates of glucose infusion, glucose disappearance, and muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. Improved muscle insulin action in the HF-fed ILK(lox/lox)HSAcre mice was associated with increased insulin-stimulated phosphorylation of Akt and increased muscle capillarization. These results suggest that ILK expression in muscle is a critical component of diet-induced insulin resistance, which possibly acts by impairing insulin signaling and insulin perfusion through capillaries. PMID:27207548

  17. Disrupted Leptin Signaling in the Lateral Hypothalamus and Ventral Premammillary Nucleus Alters Insulin and Glucagon Secretion and Protects Against Diet-Induced Obesity.

    Science.gov (United States)

    Denroche, Heather C; Glavas, Maria M; Tudurí, Eva; Karunakaran, Subashini; Quong, Whitney L; Philippe, Marion; Britton, Heidi M; Clee, Susanne M; Kieffer, Timothy J

    2016-07-01

    Leptin signaling in the central nervous system, and particularly the arcuate hypothalamic nucleus, is important for regulating energy and glucose homeostasis. However, the roles of extra-arcuate leptin responsive neurons are less defined. In the current study, we generated mice with widespread inactivation of the long leptin receptor isoform in the central nervous system via Synapsin promoter-driven Cre (Lepr(flox/flox) Syn-cre mice). Within the hypothalamus, leptin signaling was disrupted in the lateral hypothalamic area (LHA) and ventral premammillary nucleus (PMV) but remained intact in the arcuate hypothalamic nucleus and ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, and nucleus of the tractus solitarius. To investigate the role of LHA/PMV neuronal leptin signaling, we examined glucose and energy homeostasis in Lepr(flox/flox) Syn-cre mice and Lepr(flox/flox) littermates under basal and diet-induced obese conditions and tested the role of LHA/PMV neurons in leptin-mediated glucose lowering in streptozotocin-induced diabetes. Lepr(flox/flox) Syn-cre mice did not have altered body weight or blood glucose levels but were hyperinsulinemic and had enhanced glucagon secretion in response to experimental hypoglycemia. Surprisingly, when placed on a high-fat diet, Lepr(flox/flox) Syn-cre mice were protected from weight gain, glucose intolerance, and diet-induced hyperinsulinemia. Peripheral leptin administration lowered blood glucose in streptozotocin-induced diabetic Lepr(flox/flox) Syn-cre mice as effectively as in Lepr(flox/flox) littermate controls. Collectively these findings suggest that leptin signaling in LHA/PMV neurons is not critical for regulating glucose levels but has an indispensable role in the regulation of insulin and glucagon levels and, may promote the development of diet-induced hyperinsulinemia and weight gain. PMID:27183315

  18. Lactobacillus rhamnosus GG Reverses Insulin Resistance but Does Not Block Its Onset in Diet-Induced Obese Mice.

    Science.gov (United States)

    Park, Kun-Young; Kim, Bobae; Hyun, Chang-Kee

    2015-05-01

    Recently, Lactobacillus rhamnosus GG (LGG) was shown to exert insulin-sensitizing and adiposity-reducing effects in high-fat (HF) diet-fed mice. In the present study, we observed that the effects were correlated with the extent of dysbiosis induced by HF diet feeding before LGG administration. LGG-treated mice were protected from HF diet-induced adiposity and/ or insulin resistance when LGG was treated after, not along with, HF diet feeding. Results indicate that, under HF dietary condition, supplemented LGG reverses insulin resistance, but does not block its onset. PMID:25433553

  19. ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance.

    Science.gov (United States)

    Elias, Ivet; Ferré, Tura; Vilà, Laia; Muñoz, Sergio; Casellas, Alba; Garcia, Miquel; Molas, Maria; Agudo, Judith; Roca, Carles; Ruberte, Jesús; Bosch, Fatima; Franckhauser, Sylvie

    2016-08-01

    Eicosanoids, such as leukotriene B4 (LTB4) and lipoxin A4 (LXA4), may play a key role during obesity. While LTB4 is involved in adipose tissue inflammation and insulin resistance, LXA4 may exert anti-inflammatory effects and alleviate hepatic steatosis. Both lipid mediators derive from the same pathway, in which arachidonate 5-lipoxygenase (ALOX5) and its partner, arachidonate 5-lipoxygenase-activating protein (ALOX5AP), are involved. ALOX5 and ALOX5AP expression is increased in humans and rodents with obesity and insulin resistance. We found that transgenic mice overexpressing ALOX5AP in adipose tissue had higher LXA4 rather than higher LTB4 levels, were leaner, and showed increased energy expenditure, partly due to browning of white adipose tissue (WAT). Upregulation of hepatic LXR and Cyp7a1 led to higher bile acid synthesis, which may have contributed to increased thermogenesis. In addition, transgenic mice were protected against diet-induced obesity, insulin resistance, and inflammation. Finally, treatment of C57BL/6J mice with LXA4, which showed browning of WAT, strongly suggests that LXA4 is responsible for the transgenic mice phenotype. Thus, our data support that LXA4 may hold great potential for the future development of therapeutic strategies for obesity and related diseases. PMID:27207555

  20. Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3-adrenergic receptor-deficient mice promotes diet-induced obesity.

    Science.gov (United States)

    Valet, P; Grujic, D; Wade, J; Ito, M; Zingaretti, M C; Soloveva, V; Ross, S R; Graves, R A; Cinti, S; Lafontan, M; Lowell, B B

    2000-11-01

    Catecholamines play an important role in controlling white adipose tissue function and development. beta- and alpha 2-adrenergic receptors (ARs) couple positively and negatively, respectively, to adenylyl cyclase and are co-expressed in human adipocytes. Previous studies have demonstrated increased adipocyte alpha 2/beta-AR balance in obesity, and it has been proposed that increased alpha 2-ARs in adipose tissue with or without decreased beta-ARs may contribute mechanistically to the development of increased fat mass. To critically test this hypothesis, adipocyte alpha 2/beta-AR balance was genetically manipulated in mice. Human alpha 2A-ARs were transgenically expressed in the adipose tissue of mice that were either homozygous (-/-) or heterozygous (+/-) for a disrupted beta 3-AR allele. Mice expressing alpha 2-ARs in fat, in the absence of beta 3-ARs (beta 3-AR -/- background), developed high fat diet-induced obesity. Strikingly, this effect was due entirely to adipocyte hyperplasia and required the presence of alpha2-ARs, the absence of beta 3-ARs, and a high fat diet. Of note, obese alpha 2-transgenic beta 3 -/- mice failed to develop insulin resistance, which may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and not adipocyte hypertrophy. In summary, we have demonstrated that increased alpha 2/beta-AR balance in adipocytes promotes obesity by stimulating adipocyte hyperplasia. This study also demonstrates one way in which two genes (alpha 2 and beta 3-AR) and diet interact to influence fat mass. PMID:10948198

  1. Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1

    DEFF Research Database (Denmark)

    Shang, Quan; Saumoy, Monica; Holst, Jens Juul;

    2009-01-01

    Bile acid sequestrants have been shown to lower glucose levels in patients with type 2 diabetes. To investigate how colesevelam (CL) HCl improves hyperglycemia, studies were conducted in diet-induced obesity (F-DIO) rats, which develop insulin resistance when fed a high-energy (high fat....../high sucrose) diet (HE). The rats were fed HE; HE + 2% CL; HE + 0.02% SC-435 (SC), an apical sodium-dependent bile acid transporter inhibitor; and regular chow (controls). After 4 wk of treatment, both in the HE group and the SC + HE group, plasma glucose and insulin levels remained elevated compared with...... activation compared with controls. We concluded that CL reduces plasma glucose levels by improving insulin resistance in this rat model. It is unlikely that the improvement is attributable to decreased bile acid flux to the liver but is likely secondary to induced GLP-1 secretion, which improves insulin...

  2. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage.

    Science.gov (United States)

    Becattini, Barbara; Zani, Fabio; Breasson, Ludovic; Sardi, Claudia; D'Agostino, Vito Giuseppe; Choo, Min-Kyung; Provenzani, Alessandro; Park, Jin Mo; Solinas, Giovanni

    2016-09-01

    Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its activation. In this article, we describe a study in which the long-term effects of JNK1 inactivation on glucose homeostasis and oxidative stress in obese mice were investigated for the first time. Mice lacking JNK1 (JNK1(-/-)) were fed an obesogenic high-fat diet (HFD) for a long period. JNK1(-/-) mice fed an HFD for the long term had reduced expression of antioxidant genes in their skin, more skin oxidative damage, and increased epidermal thickness and inflammation compared with the effects in control wild-type mice. However, we also observed that the protection from obesity, adipose tissue inflammation, steatosis, and insulin resistance, conferred by JNK1 ablation, was sustained over a long period and was paralleled by decreased oxidative damage in fat and liver. We conclude that compounds targeting JNK1 activity in brain and adipose tissue, which do not accumulate in the skin, may be safer and most effective.-Becattini, B., Zani, F., Breasson, L., Sardi, C., D'Agostino, V. G., Choo, M.-K., Provenzani, A., Park, J. M., Solinas, G. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage. PMID:27230858

  3. Effects of physical exercise on the P38MAPK/REDD1/14-3-3 pathways in the myocardium of diet-induced obesity rats.

    Science.gov (United States)

    Pieri, B L S; Souza, D R; Luciano, T F; Marques, S O; Pauli, J R; Silva, A S R; Ropelle, E R; Pinho, R A; Lira, F S; De Souza, C T

    2014-08-01

    Obesity is associated with myocardial insulin resistance and impairment of the mammalian target of rapamycin (mTOR) signaling pathway. The activation of the mTOR cascade by exercise has been largely shown in skeletal muscle, but insufficiently analyzed in myocardial tissue. In addition, little is known regarding the mTOR upstream molecules in the hearts of obese animals and even less about the role of exercise in this process. Thus, the present study was aimed to evaluate the effects of physical exercise on P38 Mitogen-Activated Protein Kinase (P38MAPK) phosphorylation and the REDD1 (regulated in development and DNA damage responses 1) and 14-3-3 protein levels in the myocardium of diet-induced obesity (DIO) rats. After achievement of DIO and insulin resistance, Wistar rats were divided in 2 groups: sedentary obese rats and obese rats performed treadmill running (50-min/day, 5 days per week velocity of 1.0 km/h for 2 months). Forty-eight hours after the final physical exercise, the rats were killed, and the myocardial tissue was removed for Western blot analysis. DIO increased the REDD1 protein levels and reduced the 14-3-3 protein levels and P38MAPK, mTOR, P70S6k (p70 ribosomal S6 protein kinase), and 4EBP1 (4E-binding protein-1) phosphorylation. Interestingly, physical exercise reduced the REDD1 protein levels and increased the 14-3-3 protein levels and P38MAPK, mTOR, P70S6k, and 4EBP1 phosphorylation. Moreover, exercise increased the REDD1/14-3-3 association in the heart. Our results indicate that the phospho-P38MAPK, REDD1, and 14-3-3 protein levels were reduced in the myocardium of obese rats and that physical exercise increased the protein levels of these molecules. PMID:24691733

  4. Diet-induced obesity resistance of adult female mice selectively bred for increased wheel-running behavior is reversed by single perinatal exposure to a high-energy diet

    NARCIS (Netherlands)

    Guidotti, Stefano; Meyer, Neele; Przybyt, Ewa; Scheurink, Anton J.W.; Harmsen, Martin C.; Garland Jr., Theodore; van Dijk, Gertjan

    2016-01-01

    Female mice from independently bred lines previously selected over 50 generations for increased voluntary wheel-running behavior (S1, S2) resist high energy (HE) diet-induced obesity (DIO) at adulthood, even without actual access to running wheels, as opposed to randomly bred controls (CON). We inve

  5. Beneficial effects of cocoa, coffee, green tea, and garcinia complex supplement on diet induced obesity in rats

    OpenAIRE

    Huang, Chi-Chang; Tung, Yu-Tang; Huang, Wen-Ching; Chen, Yi-Ming; Hsu, Yi-Ju; Hsu, Mei-Chich

    2016-01-01

    Background Cocoa, coffee, green tea and garcinia contain large amounts of polyphenols. Polyphenols are well-known phytochemicals and found in plants, and have modulated physiological and molecular pathways that are involved in energy metabolism, adiposity, and obesity. Methods To evaluate the obesity-lowering effect of a combined extract (comprising cocoa, coffee, green tea and garcinia; CCGG) in high-energy diet (HED)-induced obese rats. Male Sprague Dawley rats (8 weeks old) were randomly d...

  6. Diet-induced Obesity and Insulin Resistance Spur Tumor Growth and Cancer Cachexia in Rats Bearing the Yoshida Sarcoma

    OpenAIRE

    Honors, Mary Ann; Kinzig, Kimberly P.

    2014-01-01

    Obesity and insulin resistance are associated with increased risk of cancer and cancer mortality. However, it is currently unknown whether they contribute to the development of cancer cachexia, a syndrome that contributes significantly to morbidity and mortality in individuals with cancer. The present experiment addresses the question of whether pre-existing obesity and insulin resistance alter tumor growth and cancer cachexia symptoms in Yoshida sarcoma bearing male rats. Obesity and insulin...

  7. Electroacupuncture Improves Insulin Resistance by Reducing Neuroprotein Y/Agouti-Related Protein Levels and Inhibiting Expression of Protein Tyrosine Phosphatase 1B in Diet-induced Obese Rats.

    Science.gov (United States)

    Liu, Xia; He, Jun-Feng; Qu, Ya-Ting; Liu, Zhi-Jun; Pu, Qing-Yang; Guo, Sheng-Tong; Du, Jia; Jiang, Peng-Fei

    2016-04-01

    Electroacupuncture (EA) has been shown to exert beneficial effects on obesity, but the mechanism is unclear. This study investigated the effects of EA on diet-induced obese (DIO) rats. Fifty male Sprague-Dawley rats were randomly divided into low-fat diet (LFD, 10 rats) and high-fat diet (HFD, 40 rats) groups. After the DIO models had been established, successful model rats were randomly divided into HFD, EA, and orlistat (OLST) groups. The EA group received EA at Zusanli (ST36) and Quchi (LI11) for 20 minutes once per day for 28 days. The OLST group was treated with orlistat by gavage. The body weight, homeostasis model assessment-insulin resistance index, adipocyte diameters, and neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B levels were significantly lower in the EA group than in the HFD group. The rats of the OLST group showed watery stools and yellow hairs whereas those of the EA group had regular stools and sleek coats. The effect of EA on weight loss may be related to improved insulin resistance caused by changes in the adipocyte size and by reductions in the expressions of neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B. This study indicates that EA may be a better method of alternative therapy for treating obesity and other metabolic diseases. PMID:27079226

  8. Fat-water MRI is sensitive to local adipose tissue inflammatory changes in a diet-induced obesity mouse model at 15T

    Science.gov (United States)

    Ong, Henry H.; Webb, Corey D.; Gruen, Marnie L.; Hasty, Alyssa H.; Gore, John C.; Welch, E. B.

    2015-03-01

    In obesity, fat-water MRI (FWMRI) methods provide valuable information about adipose tissue (AT) distribution. AT is known to undergo complex metabolic and endocrine changes in association with chronic inflammation including iron overloading. Here, we investigate the potential for FWMRI parameters (fat signal fraction (FSF), local magnetic field offset, and T2*) to be sensitive to AT inflammatory changes in an established diet-induced obesity mouse model. Male C57BL/6J mice were placed on a low fat (LFD) or a high fat diet (HFD). 3D multi- gradient-echo MRI at 15.2T was performed at baseline, 4, 8, 12, and 16 weeks after diet onset. A 3D fat-water separation algorithm and additional processing was used to generate FSF, local field offset, and T2* maps. We examined these parameters in perirenal AT ROIs from HFD and LFD mice. Results: The data suggest that FSF, local field offset, and T2* can differentiate time course behavior between inflamed and control AT (increasing FSF, decreasing local field offset, increasing followed by decreasing T2*). The biophysical mechanisms of these observed changes are not well understood and require further study. To the best of our knowledge, we report the first evidence that FWMRI can provide biomarkers sensitive to AT inflammation, and that FWMRI has the potential for longitudinal non-invasive assessment of AT inflammation in obesity.

  9. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870 on Mechanical Sensitivity in Diet-Induced Obesity Model

    Directory of Open Access Journals (Sweden)

    Fereshteh Dardmeh

    2016-01-01

    Full Text Available Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU of probiotics (Lactobacillus rhamnosus PB01, DSM14870 supplement on mechanical pain thresholds in behaving diet-induced obese (DIO mice and their normal weight (NW controls. The mice (N=24, 6-week-old male were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P<0.05. Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P<0.05 lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation.

  10. Beneficial metabolic effects of selected probiotics on diet-induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota.

    Science.gov (United States)

    Alard, Jeanne; Lehrter, Véronique; Rhimi, Moez; Mangin, Irène; Peucelle, Véronique; Abraham, Anne-Laure; Mariadassou, Mahendra; Maguin, Emmanuelle; Waligora-Dupriet, Anne-Judith; Pot, Bruno; Wolowczuk, Isabelle; Grangette, Corinne

    2016-05-01

    Alterations in gut microbiota composition and diversity were suggested to play a role in the development of obesity, a chronic subclinical inflammatory condition. We here evaluated the impact of oral consumption of a monostrain or multi-strain probiotic preparation in high-fat diet-induced obese mice. We observed a strain-specific effect and reported dissociation between the capacity of probiotics to dampen adipose tissue inflammation and to limit body weight gain. A multi-strain mixture was able to improve adiposity, insulin resistance and dyslipidemia through adipose tissue immune cell-remodelling, mainly affecting macrophages. At the gut level, the mixture modified the uptake of fatty acids and restored the expression level of the short-chain fatty acid receptor GPR43. These beneficial effects were associated with changes in the microbiota composition, such as the restoration of the abundance of Akkermansia muciniphila and Rikenellaceae and the decrease of other taxa like Lactobacillaceae. Using an in vitro gut model, we further showed that the probiotic mixture favours the production of butyrate and propionate. Our findings provide crucial clues for the design and use of more efficient probiotic preparations in obesity management and may bring new insights into the mechanisms by which host-microbe interactions govern such protective effects. PMID:26689997

  11. Rubus crataegifolius Bunge regulates adipogenesis through Akt and inhibits high-fat diet-induced obesity in rats

    OpenAIRE

    Jung, Min-Sup; Lee, Soo-Jung; Song, Yuno; Jang, Sun-Hee; Min, Wongi; Won, Chung-Kil; Kim, Hong-Duck; Kim, Tae Hoon; Cho, Jae-Hyeon

    2016-01-01

    Background Obesity is one of the greatest public health problems and major risk factors for serious metabolic diseases and significantly increases the risk of premature death. The aim of this study was to determine the inhibitory effects of Rubus crataegifolius Bunge (RCB) on adipocyte differentiation in 3 T3-L1 cells and its anti-obesity properties in high fat diet (HFD)-induced obese rats. Methods 3 T3-L1 adipocytes and HFD-induced obese rats were treated with RCB, and its effect on gene ex...

  12. Rat Models of Diet-Induced Obesity and High Fat/Low Dose Streptozotocin Type 2 Diabetes: Effect of Reversal of High Fat Diet Compared to Treatment with Enalapril or Menhaden Oil on Glucose Utilization and Neuropathic Endpoints

    OpenAIRE

    Amey Holmes; Coppey, Lawrence J.; Eric P. Davidson; Yorek, Mark A.

    2015-01-01

    We examined whether reversal of high fat diet, stimulating weight loss, compared to two treatments previously shown to have beneficial effects, could improve glucose utilization and peripheral neuropathy in animal models of obesity and type 2 diabetes. Rats were fed a high fat diet and treated with a low dose of streptozotocin to create models of diet induced obesity or type 2 diabetes, respectively. Afterwards, rats were transferred to a normal diet or treated with enalapril or dietary enric...

  13. Piperidine alkaloids from Piperretrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Jin [Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Myoung-Su; Jo, Keunae [Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Hwang, Jae-Kwan, E-mail: jkhwang@yonsei.ac.kr [Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Translational Research Center for Protein Functional Control, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2011-07-22

    Highlights: {yields} Piperidine alkaloids from Piperretrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, are isolated as the anti-obesity constituents. {yields} PRPA administration significantly reduces body weight gain without altering food intake and fat pad mass. {yields} PRPA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} PRPAs attenuate HFD-induced obesity by activating AMPK and PPAR{delta}, and regulate lipid metabolism, suggesting their potential anti-obesity effects. -- Abstract: The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor {delta} (PPAR{delta}) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPAR{delta} protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also

  14. Piperidine alkaloids from Piperretrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

    International Nuclear Information System (INIS)

    Highlights: → Piperidine alkaloids from Piperretrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, are isolated as the anti-obesity constituents. → PRPA administration significantly reduces body weight gain without altering food intake and fat pad mass. → PRPA reduces high-fat diet-induced triglyceride accumulation in liver. → PRPAs attenuate HFD-induced obesity by activating AMPK and PPARδ, and regulate lipid metabolism, suggesting their potential anti-obesity effects. -- Abstract: The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor δ (PPARδ) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPARδ protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of

  15. Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β-adrenergic system and does not compromise cardiac function.

    Science.gov (United States)

    Vileigas, Danielle F; de Deus, Adriana F; da Silva, Danielle C T; de Tomasi, Loreta C; de Campos, Dijon H S; Adorni, Caroline S; de Oliveira, Scarlet M; Sant'Ana, Paula G; Okoshi, Katashi; Padovani, Carlos R; Cicogna, Antonio C

    2016-09-01

    Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β-adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high-fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β1- and β2-adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high-fat diet-induced obesity was not effective in triggering cardiac dysfunction and impair the beta-adrenergic signaling. PMID:27582064

  16. Anti-lipogenic effect of Senna alata leaf extract in high-fat diet-induced obese mice

    Directory of Open Access Journals (Sweden)

    Jarinyaporn Naowaboot

    2016-03-01

    Conclusion: The treatment with S. alata could decrease several parameters of impaired lipid metabolism in the obese mice by downregulating sterol regulatory element binding protein 1c and PPARγ and upregulating PPARα. This study is the first report on the role of S. alata leaf extract in alleviating the abnormal lipid metabolism in obese conditions.

  17. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Wang, Dongmei; Yan, Junqiang; Chen, Jing; Wu, Wenlan; Zhu, Xiaoying; Wang, Yong

    2015-10-01

    The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin

  18. CORRELATIONS BETWEEN BLOOD PRESSURE AND BODY WEIGHT, SERUM LEPTIN IN HIGH CALORIE DIET-INDUCED OBESE RATS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Obesity is a complex,multifactorial diseasethat has beenshownto be anindependent risk factorfor the development of hypertension.Large epide-miological studies have confir med the associationbet ween body weight and blood pressure.Howev-er,the pathophysiological mechanis ms have notbeen completely understood.One problem in thestudy of the mechanis ms of obesity-related hyper-tensionis the lack of a suitable ani mal model.Thegenetic models of obesity[1]may or may not develophypertension or do not mi mic the c...

  19. Clodronate Liposomes Improve Metabolic Profile and Reduce Visceral Adipose Macrophage Content in Diet-Induced Obese Mice

    OpenAIRE

    Bin Feng; Ping Jiao; Yaohui Nie; Thomas Kim; Dale Jun; Nico van Rooijen; Zaiqing Yang; Haiyan Xu

    2011-01-01

    BACKGROUND: Obesity-related adipose inflammation has been thought to be a causal factor for the development of insulin resistance and type 2 diabetes. Infiltrated macrophages in adipose tissue of obese animals and humans are an important source for inflammatory cytokines. Clodronate liposomes can ablate macrophages by inducing apoptosis. In this study, we aim to determine whether peritoneal injection of clodronate liposomes has any beneficial effect on systemic glucose homeostasis/insulin sen...

  20. Grp78 Heterozygosity Promotes Adaptive Unfolded Protein Response and Attenuates Diet-Induced Obesity and Insulin Resistance

    OpenAIRE

    Ye, Risheng; Jung, Dae Young; Jun, John Y.; Li, Jianze; Luo, Shengzhan; Ko, Hwi Jin; Kim, Jason K.; Lee, Amy S

    2009-01-01

    OBJECTIVE To investigate the role of the endoplasmic reticulum (ER) chaperone glucose-regulated protein (GRP) 78/BiP in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. RESEARCH DESIGN AND METHODS Male Grp78 +/− mice and their wild-type littermates were subjected to a high-fat diet (HFD) regimen. Pathogenesis of obesity and type 2 diabetes was examined by multiple approaches of metabolic phenotyping. Tissue-specific insulin sensitivity was analyzed by hyperinsulinemic-eug...

  1. Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance

    OpenAIRE

    Elias, Ivet; Franckhauser, Sylvie; Ferré, Tura; Vilà, Laia; Tafuro, Sabrina; Muñoz, Sergio; Roca, Carles; Ramos, David; Pujol, Anna; Riu, Efren; Ruberte, Jesús; Bosch, Fatima

    2012-01-01

    During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adip...

  2. Retinol as a cofactor for PKCδ-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity.

    Science.gov (United States)

    Shabrova, Elena; Hoyos, Beatrice; Vinogradov, Valerie; Kim, Youn-Kyung; Wassef, Lesley; Leitges, Michael; Quadro, Loredana; Hammerling, Ulrich

    2016-03-01

    We previously defined that the mitochondria-localized PKCδ signaling complex stimulates the conversion of pyruvate to acetyl-coenzyme A by the pyruvate dehydrogenase complex. We demonstrated in vitro and ex vivo that retinol supplementation enhances ATP synthesis in the presence of the PKCδ signalosome. Here, we tested in vivo if a persistent oversupply of retinol would further impair glucose metabolism in a mouse model of diet-induced insulin resistance. We crossed mice overexpressing human retinol-binding protein (hRBP) under the muscle creatine kinase (MCK) promoter (MCKhRBP) with the PKCδ(-/-) strain to generate mice with a different status of the PKCδ signalosome and retinoid levels. Mice with a functional PKCδ signalosome and elevated retinoid levels (PKCδ(+/+)hRBP) developed the most advanced stage of insulin resistance. In contrast, elevation of retinoid levels in mice with inactive PKCδ did not affect remarkably their metabolism, resulting in phenotypic similarity between PKCδ(-/-)hRBP and PKCδ(-/-) mice. Therefore, in addition to the well-defined role of PKCδ in the etiology of metabolic syndrome, we present a novel PKCδ signaling pathway that requires retinol as a metabolic cofactor and is involved in the regulation of fuel utilization in mitochondria. The distinct role in whole-body energy homeostasis establishes the PKCδ signalosome as a promising target for therapeutic intervention in metabolic disorders.-Shabrova, E., Hoyos, B., Vinogradov, V., Kim, Y.-K., Wassef, L., Leitges, M., Quadro, L., Hammerling, U. Retinol as a cofactor for PKCδ-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity. PMID:26671999

  3. Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Jongwan Kim

    2016-02-01

    Full Text Available Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO mice. Intracerebroventricular (ICV administration of ethanol extract of ADL (ADE suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress.

  4. Hypolipidemic effect of methanol fraction of Aconitum heterophyllum wall ex Royle and the mechanism of action in diet-induced obese rats

    Directory of Open Access Journals (Sweden)

    Arun Koorappally Subash

    2012-01-01

    Full Text Available Aconitum heterophyllum is an endangered Himalayan plant included in "lekhaneyagana," a pharmacological classification mentioned by Charaka in "Charakasamhita" which means reduce excess fat. The subterranean part of the plant is used for the treatment of diseases like nervous system disorders, fever, diarrhea, obesity, etc. In the present study, we are reporting the hypolipidemic effect of methanol fraction of A. heterophyllum. The methanol extract of A. heterophyllum was orally administered in diet-induced obese rats. After four weeks treatment, blood samples were collected for the estimation of serum lipids and lecithin-cholesterol acyltransferase (LCAT. Liver was collected for the assay of HMG-CoA reductase (HMGR. The fecal samples were also collected to estimate the fecal fat content. The A. heterophyllum treatment markedly lowered total cholesterol, triglycerides and apolipoprotein B concentrations in blood serum. It also showed positive effects (increase on serum high-density lipoprotein cholesterol (HDL-c and apolipoprotein A1 concentrations. On the other hand, A. heterophyllum treatment lowered HMGR activity, which helps to reduce endogenous cholesterol synthesis and also activated LCAT, helping increase in HDL-c. An increase in fecal fat content is also an indication of the hypolipidemic effect of A. heterophyllum. The significant hypolipidemic effect of A. heterophyllum may be linked to its ability to inhibit HMGR activity and block intestinal fat absorption. The increase in HDL-c may be linked to its ability to activate LCAT enzyme.

  5. Hypolipidemic effect of methanol fraction of Aconitum heterophyllum wall ex Royle and the mechanism of action in diet-induced obese rats.

    Directory of Open Access Journals (Sweden)

    Arun Koorappally Subash

    2012-01-01

    Full Text Available Aconitum heterophyllum is an endangered Himalayan plant included in "lekhaneyagana," a pharmacological classification mentioned by Charaka in "Charakasamhita" which means reduce excess fat. The subterranean part of the plant is used for the treatment of diseases like nervous system disorders, fever, diarrhea, obesity, etc. In the present study, we are reporting the hypolipidemic effect of methanol fraction of A. heterophyllum. The methanol extract of A. heterophyllum was orally administered in diet-induced obese rats. After four weeks treatment, blood samples were collected for the estimation of serum lipids and lecithin-cholesterol acyltransferase (LCAT. Liver was collected for the assay of HMG-CoA reductase (HMGR. The fecal samples were also collected to estimate the fecal fat content. The A. heterophyllum treatment markedly lowered total cholesterol, triglycerides and apolipoprotein B concentrations in blood serum. It also showed positive effects (increase on serum high-density lipoprotein cholesterol (HDL-c and apolipoprotein A1 concentrations. On the other hand, A. heterophyllum treatment lowered HMGR activity, which helps to reduce endogenous cholesterol synthesis and also activated LCAT, helping increase in HDL-c. An increase in fecal fat content is also an indication of the hypolipidemic effect of A. heterophyllum. The significant hypolipidemic effect of A. heterophyllum may be linked to its ability to inhibit HMGR activity and block intestinal fat absorption. The increase in HDL-c may be linked to its ability to activate LCAT enzyme.

  6. Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity.

    Science.gov (United States)

    Jing, Li; Zhang, Yu; Fan, Shengjie; Gu, Ming; Guan, Yu; Lu, Xiong; Huang, Cheng; Zhou, Zhiqin

    2013-09-01

    D-limonene is a major constituent in citrus essential oil, which is used in various foods as a flavoring agent. Recently, d-limonene has been reported to alleviate fatty liver induced by a high-fat diet. Here we determined the preventive and therapeutic effects of d-limonene on metabolic disorders in mice with high-fat diet-induced obesity. In the preventive treatment, d-limonene decreased the size of white and brown adipocytes, lowered serum triglyceride (TG) and fasting blood glucose levels, and prevented liver lipid accumulations in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, d-limonene reduced serum TG, low-density lipoprotein cholesterol (LDL-c) and fasting blood glucose levels and glucose tolerance, and increased serum high-density lipoprotein cholesterol (HDL-c) in obese mice. Using a reporter assay and gene expression analysis, we found that d-limonene activated peroxisome proliferator-activated receptor (PPAR)-α signaling, and inhibited liver X receptor (LXR)-β signaling. Our data suggest that the intake of d-limonene may benefit patients with dyslipidemia and hyperglycemia and is a potential dietary supplement for preventing and ameliorating metabolic disorders. PMID:23838456

  7. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice.

    Science.gov (United States)

    Tsai, Shih-Yin; Rodriguez, Ariana A; Dastidar, Somasish G; Del Greco, Elizabeth; Carr, Kaili Lia; Sitzmann, Joanna M; Academia, Emmeline C; Viray, Christian Michael; Martinez, Lizbeth Leon; Kaplowitz, Brian Stephen; Ashe, Travis D; La Spada, Albert R; Kennedy, Brian K

    2016-08-16

    Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism. PMID:27498874

  8. Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

    2016-09-01

    Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc. PMID:26852013

  9. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity.

    Science.gov (United States)

    Solinas, Giovanni; Vilcu, Cristian; Neels, Jaap G; Bandyopadhyay, Gautam K; Luo, Jun-Li; Naugler, Willscott; Grivennikov, Sergei; Wynshaw-Boris, Anthony; Scadeng, Miriam; Olefsky, Jerrold M; Karin, Michael

    2007-11-01

    Obesity-induced insulin resistance is a major factor in the etiology of type 2 diabetes, and Jun kinases (JNKs) are key negative regulators of insulin sensitivity in the obese state. Activation of JNKs (mainly JNK1) in insulin target cells results in phosphorylation of insulin receptor substrates (IRSs) at serine and threonine residues that inhibit insulin signaling. JNK1 activation is also required for accumulation of visceral fat. Here we used reciprocal adoptive transfer experiments to determine whether JNK1 in myeloid cells, such as macrophages, also contributes to insulin resistance and central adiposity. Our results show that deletion of Jnk1 in the nonhematopoietic compartment protects mice from high-fat diet (HFD)-induced insulin resistance, in part through decreased adiposity. By contrast, Jnk1 removal from hematopoietic cells has no effect on adiposity but confers protection against HFD-induced insulin resistance by decreasing obesity-induced inflammation. PMID:17983584

  10. Effects of Anthocyanin and Flavanol Compounds on Lipid Metabolism and Adipose Tissue Associated Systemic Inflammation in Diet-Induced Obesity

    OpenAIRE

    van der Heijden, Roel A; Morrison, Martine C.; Sheedfar, Fareeba; Mulder, Petra; Schreurs, Marijke; Hommelberg, Pascal P. H.; Hofker, Marten H; Schalkwijk, Casper; Kleemann, Robert; Uwe J F Tietge; Koonen, Debby P. Y.; Heeringa, Peter

    2016-01-01

    Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential. Methods. Male C57BL/6J mice (n=52) received a control low-fat diet (LFD; 10 kcal% fat) for 6 weeks followed by 24 weeks of either LFD (n=13) or high-fat d...

  11. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice

    OpenAIRE

    Haizhao Song; Zihuan Zheng; Jianan Wu; Jia Lai; Qiang Chu; Xiaodong Zheng

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed ...

  12. Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons

    OpenAIRE

    Lambert, Charles P.; Wright, Nicole R.; Finck, Brian N.; Villareal, Dennis T

    2008-01-01

    Many obese elderly persons have impaired physical function associated with an increased chronic inflammatory response. We evaluated 12 wk of exercise (aerobic and resistance) or 12 wk of weight loss (∼7% reduction) on skeletal muscle mRNAs for toll-like receptor-4 (TLR-4), mechanogrowth factor (MGF), TNF-α, and IL-6 in 16 obese (body mass index 38 ± 2 kg/m2) older (69 ± 1 yr) physically frail individuals. Vastus lateralis muscle biopsies were obtained at 0 and 12 wk and analyzed by real-time ...

  13. Effects of Fortunella margarita fruit extract on metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Si Tan

    Full Text Available INTRODUCTION: Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle fruit extract (FME on high-fat diet-induced C57BL/6 obese mice. METHODS: The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow, high-fat diet (HF, and high-fat diet with 1% (w/w extract of kumquat (HF+FME for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. RESULTS: In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC, serum low density lipoprotein cholesterol (LDL-c levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG, serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. CONCLUSION: Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.

  14. Variation in type 2 diabetes--related traits in mouse strains susceptible to diet-induced obesity

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Rim, J. S.; Koza, R. A.; Kozak, L. P.

    2003-01-01

    Roč. 52, č. 8 (2003), s. 1958-1966. ISSN 0012-1797 Institutional research plan: CEZ:AV0Z5011922 Keywords : inbred mice * insulin resistance * obesity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 8.298, year: 2003

  15. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway.

    Science.gov (United States)

    Ding, Lili; Li, Jinmei; Song, Baoliang; Xiao, Xu; Zhang, Binfeng; Qi, Meng; Huang, Wendong; Yang, Li; Wang, Zhengtao

    2016-08-01

    Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance. PMID:27208389

  16. Synergistic effect of CART (cocaine and amphetamine regulated transcript) peptide and cholecystokinin in lean and diet-induced obese mice

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Matyšková, Resha; Blokešová, Darja; Haugvicová, Renata; Železná, Blanka; Maletínská, Lenka

    Paris: -, 2007. [World Congress on Prevention and Therapies against Obesity /2./. 14.06.2007-15.06.2007, Paris] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : cocaine * cholecystokinin * synergy Subject RIV: CE - Biochemistry

  17. Magnolia Extract (BL153 Ameliorates Kidney Damage in a High Fat Diet-Induced Obesity Mouse Model

    Directory of Open Access Journals (Sweden)

    Wenpeng Cui

    2013-01-01

    Full Text Available Accumulating evidence demonstrated that obesity is a risk factor for renal structural and functional changes, leading to the end-stage renal disease which imposes a heavy economic burden on the community. However, no effective therapeutic method for obesity-associated kidney disease is available. In the present study, we explored the therapeutic potential of a magnolia extract (BL153 for treating obesity-associated kidney damage in a high fat diet- (HFD- induced mouse model. The results showed that inflammation markers (tumor necrosis factor-α and plasminogen activator inhibitor-1 and oxidative stress markers (3-nitrotyrosine and 4-hydroxy-2-nonenal were all significantly increased in the kidney of HFD-fed mice compared to mice fed with a low fat diet (LFD. Additionally, proteinuria and renal structure changes in HFD-fed mice were much more severe than that in LFD-fed mice. However, all these alterations were attenuated by BL153 treatment, accompanied by upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α and hexokinase II (HK II expression in the kidney. The present study indicates that BL153 administration may be a novel approach for renoprotection in obese individuals by antiinflammation and anti-oxidative stress most likely via upregulation of PGC-1α and HK II signal in the kidney.

  18. Effect of a genetic locus on rat chromosome 20 on metabolic rate in high-fat diet-induced obesity

    Czech Academy of Sciences Publication Activity Database

    Hojná, S.; Lotfipour, S.; Kuneš, Jaroslav; Křen, V.; Pravenec, M.; Pausová, Z.

    Fyziologický ústav AV ČR, v. v. i.. Roč. 57, č. 3 (2008), 46P-46P ISSN 0862-8408. [International SHR Meeting /13./. 20.06.2008-22.06.2008, Praha] Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * rat chromosome 20 * high-fat diet * obesity Subject RIV: ED - Physiology

  19. Propionyl-L-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity.

    Directory of Open Access Journals (Sweden)

    Carmen Mingorance

    Full Text Available AIMS: Obesity is a primary contributor to acquired insulin resistance leading to the development of type 2 diabetes and cardiovascular alterations. The carnitine derivate, propionyl-L-carnitine (PLC, plays a key role in energy control. Our aim was to evaluate metabolic and cardiovascular effects of PLC in diet-induced obese mice. METHODS: C57BL/6 mice were fed a high-fat diet for 9 weeks and then divided into two groups, receiving either free- (vehicle-HF or PLC-supplemented water (200 mg/kg/day during 4 additional weeks. Standard diet-fed animals were used as lean controls (vehicle-ST. Body weight and food intake were monitored. Glucose and insulin tolerance tests were assessed, as well as the HOMA(IR, the serum lipid profile, the hepatic and muscular mitochondrial activity and the tissue nitric oxide (NO liberation. Systolic blood pressure, cardiac and endothelial functions were also evaluated. RESULTS: Vehicle-HF displayed a greater increase of body weight compared to vehicle-ST that was completely reversed by PLC treatment without affecting food intake. PLC improved the insulin-resistant state and reversed the increased total cholesterol but not the increase in free fatty acid, triglyceride and HDL/LDL ratio induced by high-fat diet. Vehicle-HF exhibited a reduced cardiac output/body weight ratio, endothelial dysfunction and tissue decrease of NO production, all of them being improved by PLC treatment. Finally, the decrease of hepatic mitochondrial activity by high-fat diet was reversed by PLC. CONCLUSIONS: Oral administration of PLC improves the insulin-resistant state developed by obese animals and decreases the cardiovascular risk associated to this metabolic alteration probably via correction of mitochondrial function.

  20. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Wahlang, Banrida [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Song, Ming [Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Beier, Juliane I. [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Cameron Falkner, K. [Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Al-Eryani, Laila [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Clair, Heather B.; Prough, Russell A. [Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Osborne, Tanasa S.; Malarkey, David E. [Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Christopher States, J. [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Cave, Matthew C., E-mail: matt.cave@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); The Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206 (United States)

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  1. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  2. Fenofibrate inhibits adipocyte hypertrophy and insulin resistance by activating adipose PPARα in high fat diet-induced obese mice

    OpenAIRE

    Jeong, Sunhyo; Yoon, Michung

    2009-01-01

    Peroxisome proliferator-activated receptor α (PPARα) activation in rodents is thought to improve insulin sensitivity by decreasing ectopic lipids in non-adipose tissues. Fenofibrate, a lipid-modifying agent that acts as a PPARα agonist, may prevent adipocyte hypertrophy and insulin resistance by increasing intracellular lipolysis from adipose tissue. Consistent with this hypothesis, fenofibrate decreased visceral fat mass and adipocyte size in high fat diet-fed obese mice, and concomitantly i...

  3. Spontaneous Activity, Economy of Activity, and Resistance to Diet-Induced Obesity in Rats Bred for High Intrinsic Aerobic Capacity

    OpenAIRE

    Novak, Colleen M.; Escande, Carlos; Burghardt, Paul R.; Zhang, Minzhi; Barbosa, Maria Teresa; Chini, Eduardo N.; Britton, Steven L.; Koch, Lauren G.; Akil, Huda; James A Levine

    2010-01-01

    Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and meta...

  4. Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats

    OpenAIRE

    Kathleen Kauter; Md Ashraful Alam; Lindsay Brown

    2013-01-01

    Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated th...

  5. Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Růžičková, Jana; Rossmeisl, Martin; Pražák, Tomáš; Flachs, Pavel; Šponarová, Jana; Vecka, M.; Tvrzická, E.; Bryhn, M.; Kopecký, Jan

    2004-01-01

    Roč. 39, č. 12 (2004), s. 1177-1185. ISSN 0024-4201 R&D Projects: GA ČR GA303/02/1220; GA ČR GP303/03/P127; GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5011922 Keywords : fat * obesity * diet Subject RIV: CE - Biochemistry Impact factor: 1.679, year: 2004

  6. Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice.

    Science.gov (United States)

    Satoh, Masashi; Hoshino, Miyuki; Fujita, Koki; Iizuka, Misao; Fujii, Satoshi; Clingan, Christopher S; Van Kaer, Luc; Iwabuchi, Kazuya

    2016-01-01

    It has been shown that CD1d expression and glycolipid-reactive, CD1d-restricted NKT cells exacerbate the development of obesity and insulin resistance in mice. However, the relevant CD1d-expressing cells that influence the effects of NKT cells on the progression of obesity remain incompletely defined. In this study, we have demonstrated that 3T3-L1 adipocytes can present endogenous ligands to NKT cells, leading to IFN-γ production, which in turn, stimulated 3T3-L1 adipocytes to enhance expression of CD1d and CCL2, and decrease expression of adiponectin. Furthermore, adipocyte-specific CD1d deletion decreased the size of the visceral adipose tissue mass and enhanced insulin sensitivity in mice fed a high-fat diet (HFD). Accordingly, NKT cells were less activated, IFN-γ production was significantly reduced, and levels of adiponectin were increased in these animals as compared with control mice on HFD. Importantly, macrophage recruitment into the adipose tissue of adipocyte-specific CD1d-deficient mice was significantly blunted. These findings indicate that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. PMID:27329323

  7. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.

    LENUS (Irish Health Repository)

    Lynch, Lydia

    2012-09-21

    Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.

  8. Lactobionic acid reduces body weight gain in diet-induced obese rats by targeted inhibition of galectin-1.

    Science.gov (United States)

    Mukherjee, Rajib; Yun, Jong Won

    2015-08-01

    Galectin-1 (GAL1), an animal lectin with a carbohydrate recognition domain, is known for its roles in cancer, tumor progression, as well as obesity and related complications. Here, we investigated the anti-obesity effect of lactobionic acid (LBA), a GAL1 inhibitor, both in vitro and in vivo. LBA treatment significantly reduced lipogenic capacity of both 3T3-L1 and HIB1B adipocytes through down-regulation of major adipogenic transcription factors at both mRNA and protein levels. Moreover, oral administration and intraperitoneal injection of LBA in Sprague-Dawley male rats fed a high fat diet caused marked reduction of body weight gain as well as improvement of related metabolic parameters. Important lipogenic transcription factors were also down-regulated in LBA-treated rats, resulting in attenuated lipogenesis and fat accumulation. Collectively, pharmaceutical targeting of GAL1 using LBA would be a novel therapeutic approach for the treatment of obesity. PMID:26116537

  9. Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression.

    Directory of Open Access Journals (Sweden)

    Susan E Olivo-Marston

    Full Text Available Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO would increase (and CR would decrease colon tumorigenesis in the mouse azoxymethane (AOM model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1 control diet; 2 30% CR diet; or 3 DIO diet. Mice were euthanized at week 5 (n = 12/group, 10 (n = 12/group, and 20 (n = 20/group after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1, IGF binding protein 3 (IGFBP-3, adipokines, proliferation, apoptosis, and expression of microRNAs (miRs were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat, while CR induced a lean phenotype (∼14% body fat; controls were intermediate (∼26% body fat. Relative to controls, DIO increased (and CR decreased the number of colon tumors (p = 0.01, cytokines (p<0.001, IGF-1 (p = 0.01, and proliferation (p<0.001. DIO decreased (and CR increased IGFBP-3 and apoptosis (p<0.001. miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs.

  10. Lipid-Lowering Effects of Pediococcus acidilactici M76 Isolated from Korean Traditional Makgeolli in High Fat Diet-Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Yeon-Jeong Moon

    2014-03-01

    Full Text Available The effect of Pediococcus acidilactici M76 (lactic acid bacteria isolated from makgeolli on mice fed a high fat diet was investigated to clarify the lipid lowering function. C57BL/6J male mice were randomly divided into a normal diet (ND group, high fat diet (HD group, HD plus Pediococcus acidilactici DSM 20284 reference strain (PR group, and HD plus Pediococcus acidilactici M76 strain (PA groups. The lyophilized PA and PR strain were dissolved in distilled water at a final concentration of 1.25 × 109 cfu/mL and was given orally to animals at a dose of 4 mL/kg body weight for 12 weeks. The PA group had a lower final body weight, adipose tissue weight, and lipid profile than those in the HD group. Additionally, level of ACC, FAS and PPAR-γ, a key lipid synthesis enzyme, was markedly suppressed in the PA compared to those in the HD group. These data suggest that P. acidilactici M76 may exert a lipid-lowering effect in high fat diet- induced obese mice.

  11. Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Ojo, Opeolu O; Srinivasan, Dinesh K; Owolabi, Bosede O; McGahon, Mary K; Moffett, R Charlotte; Curtis, Tim M; Conlon, J Michael; Flatt, Peter R; Abdel-Wahab, Yasser H A

    2016-08-01

    The frog skin host-defense peptide tigerinin-1R stimulates insulin release in vitro and improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observations by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg4]tigerinin-1R in mice with diet-induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on KATP and L-type Ca2+ channels in BRIN-BD11 clonal β cells. Non-fasting plasma glucose and glucagon concentrations were significantly (pinsulin increased by twice daily treatment with [Arg4]tigerinin-1R (75 nmol/kg body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (pinsulin. The peptide blocked KATP channels and, consistent with this, improved beta cell responses of isolated islets to a range of secretagogues. Peptide administration resulted in up-regulation of key functional genes in islets involved insulin secretion (Abcc8, Kcnj11, Cacna1c and Slc2a2) and in skeletal muscle involved with insulin action (Insr, Irs1, Pdk1, Pik3ca, and Slc2a4). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes. PMID:26966929

  12. Urinary metabolomic profiling in mice with diet-induced obesity and type 2 diabetes mellitus after treatment with metformin, vildagliptin and their combination.

    Science.gov (United States)

    Pelantová, Helena; Bugáňová, Martina; Holubová, Martina; Šedivá, Blanka; Zemenová, Jana; Sýkora, David; Kaválková, Petra; Haluzík, Martin; Železná, Blanka; Maletínská, Lenka; Kuneš, Jaroslav; Kuzma, Marek

    2016-08-15

    Metformin, vildagliptin and their combination are widely used for the treatment of diabetes, but little is known about the metabolic responses to these treatments. In the present study, NMR-based metabolomics was applied to detect changes in the urinary metabolomic profile of a mouse model of diet-induced obesity in response to these treatments. Additionally, standard biochemical parameters and the expression of enzymes involved in glucose and fat metabolism were monitored. Significant correlations were observed between several metabolites (e.g., N-carbamoyl-β-alanine, N1-methyl-4-pyridone-3-carboxamide, N1-methyl-2-pyridone-5-carboxamide, glucose, 3-indoxyl sulfate, dimethylglycine and several acylglycines) and the area under the curve of glucose concentrations during the oral glucose tolerance test. The present study is the first to present N-carbamoyl-β-alanine as a potential marker of type 2 diabetes mellitus and consequently to demonstrate the efficacies of the applied antidiabetic interventions. Moreover, the elevated acetate level observed after vildagliptin administration might reflect increased fatty acid oxidation. PMID:27164444

  13. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

    Directory of Open Access Journals (Sweden)

    Eu Chia

    2010-07-01

    Full Text Available Abstract Background The metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL, an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR. Glycyrrhizic acid (GA, a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state. Results Oral administration of 100 mg/kg of GA to high-fat diet-induced obese rats for 28 days led to significant reduction in blood glucose concentration and improvement in insulin sensitivity as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR (p Conclusion In conclusion, GA may be a potential compound in improving dyslipidaemia by selectively inducing LPL expression in non-hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement in insulin sensitivity, which may be associated with a decrease in tissue lipid deposition. The HDL-raising effect of GA suggests the antiatherosclerotic properties of GA.

  14. Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice.

    Directory of Open Access Journals (Sweden)

    Yongjie Ma

    Full Text Available Pregnane X receptor (PXR is known to function as a xenobiotic sensor to regulate xenobiotic metabolism through selective transcription of genes responsible for maintaining physiological homeostasis. Here we report that the activation of PXR by pregnenolone 16α-carbonitrile (PCN in AKR/J mice can prevent the development of high-fat diet-induced obesity and insulin resistance. The beneficial effects of PCN treatment are seen with reduced lipogenesis and gluconeogenesis in the liver, and lack of hepatic accumulation of lipid and lipid storage in the adipose tissues. RT-PCR analysis of genes involved in gluconeogenesis, lipid metabolism and energy homeostasis reveal that PCN treatment on high-fat diet-fed mice reduces expression in the liver of G6Pase, Pepck, Cyp7a1, Cd36, L-Fabp, Srebp, and Fas genes and slightly enhances expression of Cyp27a1 and Abca1 genes. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue show that PCN treatment reduces expression of Pparγ2, Acc1, Cd36, but increases expression of Cpt1b and Pparα genes in mice fed with high-fat diet. Similarly, PCN treatment of animals on high-fat diet increases expression in brown adipose tissue of Pparα, Hsl, Cpt1b, and Cd36 genes, but reduces expression of Acc1 and Scd-1 genes. PXR activation by PCN in high-fat diet fed mice also increases expression of genes involved in thermogenesis in brown adipose tissue including Dio2, Pgc-1α, Pgc-1β, Cidea, and Ucp-3. These results verify the important function of PXR in lipid and energy metabolism and suggest that PXR represents a novel therapeutic target for prevention and treatment of obesity and insulin resistance.

  15. Carnosic acid as a major bioactive component in rosemary extract ameliorates high-fat-diet-induced obesity and metabolic syndrome in mice.

    Science.gov (United States)

    Zhao, Yantao; Sedighi, Rashin; Wang, Pei; Chen, Huadong; Zhu, Yingdong; Sang, Shengmin

    2015-05-20

    In this study, we investigated the preventive effects of carnosic acid (CA) as a major bioactive component in rosemary extract (RE) on high-fat-diet-induced obesity and metabolic syndrome in mice. The mice were given a low-fat diet, a high-fat diet or a high-fat diet supplemented with either 0.14% or 0.28% (w/w) CA-enriched RE (containing 80% CA, RE#1L and RE#1H), or 0.5% (w/w) RE (containing 45% CA, RE#2), for a period of 16 weeks. There was the same CA content in the RE#1H and RE#2 diets and half of this amount in the RE#1L diet. The dietary RE supplementation significantly reduced body weight gain, percent of fat, plasma ALT, AST, glucose, insulin levels, liver weight, liver triglyceride, and free fatty acid levels in comparison with the mice fed with a HF diet without RE treatment. RE administration also decreased the levels of plasma and liver malondialdehyde, advanced glycation end products (AGEs), and the liver expression of receptor for AGE (RAGE) in comparison with those for mice of the HF group. Histological analyses of liver samples showed decreased lipid accumulation in hepatocytes in mice administrated with RE in comparison with that of HF-diet-fed mice. Meanwhile, RE administration enhanced fecal lipid excretion to inhibit lipid absorption and increased the liver GSH/GSSG ratio to perform antioxidant activity compared with HF group. Our results demonstrate that rosemary is a promising dietary agent to reduce the risk of obesity and metabolic syndrome. PMID:25929334

  16. Citrus aurantium and Rhodiola rosea in combination reduce visceral white adipose tissue and increase hypothalamic norepinephrine in a rat model of diet-induced obesity.

    Science.gov (United States)

    Verpeut, Jessica L; Walters, Amy L; Bello, Nicholas T

    2013-06-01

    Extracts from the immature fruit of Citrus aurantium are often used for weight loss but are reported to produce adverse cardiovascular effects. Root extracts of Rhodiola rosea have notable antistress properties. The hypothesis of these studies was that C aurantium (6% synephrine) and R rosea (3% rosavins, 1% salidroside) in combination would improve diet-induced obesity alterations in adult male Sprague-Dawley rats. In normal-weight animals fed standard chow, acute administration of C aurantium (1-10 mg/kg) or R rosea (2-20 mg/kg) alone did not reduce deprivation-induced food intake, but C aurantium (5.6 mg/kg) + R rosea (20 mg/kg) produced a 10.5% feeding suppression. Animals maintained (13 weeks) on a high-fat diet (60% fat) were exposed to 10-day treatments of C aurantium (5.6 mg/kg) or R rosea (20 mg/kg) alone or in combination. Additional groups received vehicle (2% ethanol) or were pair fed to the C aurantium + R rosea group. Although high-fat diet intake and weight loss were not influenced, C aurantium + R rosea had a 30% decrease in visceral fat weight compared with the other treatments. Only the C aurantium group had an increased heart rate (+7%) compared with vehicle. In addition, C aurantium + R rosea administration resulted in an elevation (+15%) in hypothalamic norepinephrine and an elevation (+150%) in frontal cortex dopamine compared with the pair-fed group. These initial findings suggest that treatments of C aurantium + R rosea have actions on central monoamine pathways and have the potential to be beneficial for the treatment of obesity. PMID:23746567

  17. The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Michel Alexander Steiner

    2013-12-01

    Full Text Available The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1 in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO associated with metabolic syndrome (MetS. Rats were fed either standard chow (SC or a cafeteria (CAF diet comprised of intermittent human snacks and a constant free choice between a HF/sweet (HF/S diet and SC for 13 weeks. Thereafter the SC group was treated with vehicle (for 4 weeks and the CAF group was divided into a vehicle and an ACT-335827 treatment group. Energy and water intake, food preference, and indicators of MetS (abdominal obesity, glucose homeostasis, plasma lipids, and blood pressure were monitored. Hippocampus-dependent memory, which can be impaired by DIO, was assessed. CAF diet fed rats treated with ACT-335827 consumed less of the HF/S diet and more of the SC, but did not change their snack or total kcal intake compared to vehicle-treated rats. ACT-335827 increased water intake and the high-density lipoprotein associated cholesterol proportion of total circulating cholesterol. ACT-335827 slightly increased body weight gain (4% versus controls and feed efficiency in the absence of hyperphagia. These effects were not associated with significant changes in the elevated fasting glucose and triglyceride (TG plasma levels, glucose intolerance, elevated blood pressure, and adiposity due to CAF diet consumption. Neither CAF diet consumption alone nor ACT-335827 affected memory. In conclusion, the main metabolic characteristics associated with DIO and MetS in rats remained unaffected by chronic ACT-335827 treatment, suggesting that pharmacological OXR-1 blockade has minimal impact in this

  18. Effects of treadmill exercise on skeletal muscle mTOR signaling pathway in high-fat diet-induced obese mice.

    Science.gov (United States)

    Woo, Jin Hee; Shin, Ki Ok; Lee, Yul Hyo; Jang, Ki Soeng; Bae, Ju Yong; Roh, Hee Tae

    2016-04-01

    [Purpose] The aim of this study was to investigate the effects of regular treadmill exercise on skeletal muscle Rictor-Akt and mTOR-Raptor-S6K1 signaling pathway in high-fat diet-induced obese mice. [Subjects and Methods] Four- week-old C57BL/6 mice were adopted and classified into normal diet group (ND, n = 10), normal diet and training group (NDT, n = 10), high-fat diet group (HF, n = 10), and high-fat diet and training group (HFT, n = 10). The exercise program consisted of a treadmill exercise provided at low intensity for 1-4 weeks, and moderate intensity for 5-8 weeks. [Results] The Western blot method was used to measure the expression of mTOR, Raptor, S6K1, Rictor, and Akt proteins in the soleus muscle. mTOR levels were significantly higher in the HF group than in the ND and NDT groups. Raptor/mTORC1 and S6K1 levels were significantly higher in the HF group than in all the other groups. Akt levels were significantly lower in the HF group than in the NDT group. The risk of obesity may be associated with the overactivation of the mTOR-Raptor-S6K1 signaling pathway and a decrease in Akt levels. [Conclusion] This study also indicates that performing aerobic exercise may be associated with the downregulation of the mTOR-Raptor-S6K1 pathway. PMID:27190464

  19. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    Science.gov (United States)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan; Badran, Samir; Arco, Rocío; Pavón, Francisco Javier; Serrano, Antonia; Rivera, Patricia; Decara, Juan; Cuesta, Antonio Luis; Rodríguez-de-Fonseca, Fernando

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats. PMID:27333268

  20. The Extract of Herbal Medicines Activates AMP-Activated Protein Kinase in Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Hye-Yeon Shin

    2013-01-01

    Full Text Available Our study investigated whether the extract of six herbal medicines (OB-1 has an inhibitory effect on obesity. High-fat diet-(HFD- induced rats and controls were treated with 40 mg/100 g body weight of OB-1 or saline once a day for 5 weeks. After significant changes in body weight were induced, OB-1 and saline were administered to each subgroup of HFD and control groups for additional 5 weeks. No statistically significant decrease of body weight in OB-1-treated rats was found compared to controls. However, OB-1-treated rats were found to be more active in an open-field test and have a reduction in the size of adipocytes compared to controls. We observed no changes in the mRNA expressions of leptin and adiponectin from adipocytes between OB-1- and saline-treated rats with HFD-induced obesity group. However, OB-1 treatments were shown to be inversely correlated with accumulation of lipid droplets in liver tissue, suggesting that OB-1 could inhibit a lipid accumulation by blocking the pathway related to lipid metabolism. Moreover, the phosphorylation of AMP-activated protein kinase (AMPK was significantly increased in OB-1-treated rats with HFD compared to controls. These results suggest that OB-1 has no direct antiobesity effect and, however, could be a regulator of cellular metabolism.

  1. Nutrigenomics of high fat diet induced obesity in mice suggests relationships between susceptibility to fatty liver disease and the proteasome.

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    Helen Waller-Evans

    Full Text Available Nutritional factors play important roles in the etiology of obesity, type 2 diabetes mellitus and their complications through genotype x environment interactions. We have characterised molecular adaptation to high fat diet (HFD feeding in inbred mouse strains widely used in genetic and physiological studies. We carried out physiological tests, plasma lipid assays, obesity measures, liver histology, hepatic lipid measurements and liver genome-wide gene transcription profiling in C57BL/6J and BALB/c mice fed either a control or a high fat diet. The two strains showed marked susceptibility (C57BL/6J and relative resistance (BALB/c to HFD-induced insulin resistance and non alcoholic fatty liver disease (NAFLD. Global gene set enrichment analysis (GSEA of transcriptome data identified consistent patterns of expression of key genes (Srebf1, Stard4, Pnpla2, Ccnd1 and molecular pathways in the two strains, which may underlie homeostatic adaptations to dietary fat. Differential regulation of pathways, including the proteasome, the ubiquitin mediated proteolysis and PPAR signalling in fat fed C57BL/6J and BALB/c suggests that altered expression of underlying diet-responsive genes may be involved in contrasting nutrigenomic predisposition and resistance to insulin resistance and NAFLD in these models. Collectively, these data, which further demonstrate the impact of gene x environment interactions on gene expression regulations, contribute to improved knowledge of natural and pathogenic adaptive genomic regulations and molecular mechanisms associated with genetically determined susceptibility and resistance to metabolic diseases.

  2. PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity Downstream of TOR and Brummer ATGL Lipase

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    Soda Balla Diop

    2015-03-01

    Full Text Available Obesity and metabolic syndrome are associated with an increased risk for lipotoxic cardiomyopathy, which is strongly correlated with excessive accumulation of lipids in the heart. Obesity- and type-2-diabetes-related disorders have been linked to altered expression of the transcriptional cofactor PGC-1α, which regulates the expression of genes involved in energy metabolism. Using Drosophila, we identify PGC-1/spargel (PGC-1/srl as a key antagonist of high-fat diet (HFD-induced lipotoxic cardiomyopathy. We find that HFD-induced lipid accumulation and cardiac dysfunction are mimicked by reduced PGC-1/srl function and reversed by PGC-1/srl overexpression. Moreover, HFD feeding lowers PGC-1/srl expression by elevating TOR signaling and inhibiting expression of the Drosophila adipocyte triglyceride lipase (ATGL (Brummer, both of which function as upstream modulators of PGC-1/srl. The lipogenic transcription factor SREBP also contributes to HFD-induced cardiac lipotoxicity, likely in parallel with PGC-1/srl. These results suggest a regulatory network of key metabolic genes that modulates lipotoxic heart dysfunction.

  3. Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

    International Nuclear Information System (INIS)

    Research highlights: → NDGA decreases high-fat diet-induced body weight gain and adiposity. → NDGA reduces high-fat diet-induced triglyceride accumulation in liver. → NDGA improves lipid storage in vitro through altering lipid regulatory proteins. → Inhibition of lipid storage in vivo and in vitro is mediated by AMPK activation. -- Abstract: Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. We evaluated body weight, adiposity, liver histology, and hepatic triglyceride content in high-fat diet (HFD)-fed C57BL/6J mice treated with NDGA. In addition, we characterized the underlying mechanism of NDGA's effects in HepG2 hepatocytes by Western blot and RT-PCR analysis. NDGA (100 or 200 mg/kg/day) reduced weight gain, fat pad mass, and hepatic triglyceride accumulation, and improved serum lipid parameters in mice fed a HFD for 8 weeks. NDGA significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the liver and in HepG2 hepatocytes. NDGA downregulated the level of mature SREBP-1 and its target genes (acetyl-CoA carboxylase and fatty acid synthase), but, it upregulated expression of genes involved in fatty acid oxidation, such as peroxisome proliferator-activated receptor (PPAR)α, PPARγ coactivator-1, carnitine palmitoyl transferase-1, and uncoupling protein-2. The specific AMPK inhibitor compound C attenuated the effects of NDGA on expression of lipid metabolism-related proteins in HepG2 hepatocytes. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.

  4. Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung-Su; Kim, Daeyoung; Jo, Keunae [Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Hwang, Jae-Kwan, E-mail: jkhwang@yonsei.ac.kr [Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Translational Research Center for Protein Function Control, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)

    2010-10-08

    Research highlights: {yields} NDGA decreases high-fat diet-induced body weight gain and adiposity. {yields} NDGA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} NDGA improves lipid storage in vitro through altering lipid regulatory proteins. {yields} Inhibition of lipid storage in vivo and in vitro is mediated by AMPK activation. -- Abstract: Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. We evaluated body weight, adiposity, liver histology, and hepatic triglyceride content in high-fat diet (HFD)-fed C57BL/6J mice treated with NDGA. In addition, we characterized the underlying mechanism of NDGA's effects in HepG2 hepatocytes by Western blot and RT-PCR analysis. NDGA (100 or 200 mg/kg/day) reduced weight gain, fat pad mass, and hepatic triglyceride accumulation, and improved serum lipid parameters in mice fed a HFD for 8 weeks. NDGA significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the liver and in HepG2 hepatocytes. NDGA downregulated the level of mature SREBP-1 and its target genes (acetyl-CoA carboxylase and fatty acid synthase), but, it upregulated expression of genes involved in fatty acid oxidation, such as peroxisome proliferator-activated receptor (PPAR){alpha}, PPAR{gamma} coactivator-1, carnitine palmitoyl transferase-1, and uncoupling protein-2. The specific AMPK inhibitor compound C attenuated the effects of NDGA on expression of lipid metabolism-related proteins in HepG2 hepatocytes. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.

  5. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    International Nuclear Information System (INIS)

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets

  6. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

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    Kanno, Ayumi, E-mail: akanno@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Asahara, Shun-ichiro, E-mail: asahara@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Masuda, Katsuhisa, E-mail: katsuhisa.m.0707@gmail.com [Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142 (Japan); Matsuda, Tomokazu, E-mail: tomokazu@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kimura-Koyanagi, Maki, E-mail: koyanagi@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Seino, Susumu, E-mail: seino@med.kobe-u.ac.jp [Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047 (Japan); Ogawa, Wataru, E-mail: ogawa@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kido, Yoshiaki, E-mail: kido@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142 (Japan)

    2015-03-13

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.

  7. Diet induced thermogenesis

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    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  8. Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer✩

    OpenAIRE

    Liu, Zhenhua; Brooks, Ryan S.; Ciappio, Eric D.; Kim, Susan J; Crott, Jimmy W.; Bennett, Grace; Greenberg, Andrew S.; Mason, Joel B.

    2011-01-01

    Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An infl...

  9. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice

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    Soyoung Park

    2016-01-01

    Full Text Available Korean pine nut oil (PNO has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO (PC, SC or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD, for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively compared with SHFD. Hepatic triacylglycerol (TG level was significantly lower in PHFD than the SHFD (26% lower. PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response.

  10. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Park, Soyoung; Shin, Sunhye; Lim, Yeseo; Shin, Jae Hoon; Seong, Je Kyung; Han, Sung Nim

    2016-01-01

    Korean pine nut oil (PNO) has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD) can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO) (PC, SC) or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD), for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively) compared with SHFD. Hepatic triacylglycerol (TG) level was significantly lower in PHFD than the SHFD (26% lower). PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT) 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR) and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response. PMID:26805879

  11. Fenugreek Seed Extract Inhibit Fat Accumulation and Ameliorates Dyslipidemia in High Fat Diet-Induced Obese Rats

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    Parveen Kumar

    2014-01-01

    Full Text Available This study investigated the inhibitory effect of aqueous extract of Trigonella foenum-graecum seeds (AqE-TFG on fat accumulation and dyslipidemia in high fat diet- (HFD- induced obese rats. Female Wistar rats were fed with HFD ad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days + AqE-TFG (0.5 and 1.0 g/kg or orlistat (10 mg/kg from day 8 to 28, respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI, white adipose tissue (WAT weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST, alanine amino transferase (ALT, and lactate dehydrogenase (LDH levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS and elevated the antioxidant enzyme (glutathione (GSH, superoxide dismutase (SOD, and catalase (CAT levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS and glucose-6-phosphate dehydrogenase (G6PD activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes.

  12. The Resin from Protium heptaphyllum Prevents High-Fat Diet-Induced Obesity in Mice: Scientific Evidence and Potential Mechanisms

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    Karine Maria Martins Bezerra Carvalho

    2015-01-01

    Full Text Available Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism and to have beneficial effects on metabolic disorders. The present study investigated the antiobesity properties of resin from Protium heptaphyllum (RPH and the possible mechanisms in mice fed a high-fat diet (HFD for 15 weeks. Mice treated with RPH showed decreases in body weight, net energy intake, abdominal fat accumulation, plasma glucose, amylase, lipase, triglycerides, and total cholesterol relative to their respective controls, which were RPH unfed. Additionally, RPH treatment, while significantly elevating the plasma level of ghrelin hormone, decreased the levels of insulin, leptin, and resistin. Besides, HFD-induced increases in plasma levels of proinflammatory mediators TNF-α, IL-6, and MCP-1 were significantly lowered by RPH. Furthermore, in vitro studies revealed that RPH could significantly inhibit the lipid accumulation in 3T3-L1 adipocytes (measured by Oil-Red O staining at concentrations up to 50 μg/mL. These findings suggest that the antiobese potential of RPH is largely due to its modulatory effects on various hormonal and enzymatic secretions related to fat and carbohydrate metabolism and to the regulation of obesity-associated inflammation.

  13. Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice

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    Sadler, Natalie C.; Angel, Thomas E.; Lewis, Michael P.; Pederson, Leeanna M.; Chauvigne-Hines, Lacie M.; Wiedner, Susan D.; Zink, Erika M.; Smith, Richard D.; Wright, Aaron T.

    2012-10-24

    High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD or if the mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar or elevated relative to standard diet (SD) mice, thereby IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, β-oxidation, and respiratory chain function at levels similar to or higher than SD mice.

  14. Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.

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    Eliete Dalla Corte Frantz

    Full Text Available BACKGROUND: The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF diet. METHODS: C57BL/6 mice fed a HF diet (8 weeks were treated with aliskiren (50 mg/kg/day, enalapril (30 mg/kg/day or losartan (10 mg/kg/day for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis. RESULTS: All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression. CONCLUSION: Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7 /Mas receptor axis and adiponectin levels.

  15. Diet-induced obesity elevates colonic TNF-alpha in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer

    Science.gov (United States)

    Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induce...

  16. Bitter melon (Momordica charantia L.) inhibits adipocyte hypertrophy and down regulates lipogenic gene expression in adipose tissue of diet-induced obese rats.

    Science.gov (United States)

    Huang, Hui-Ling; Hong, Ya-Wen; Wong, You-Hong; Chen, Ying-Nien; Chyuan, Jong-Ho; Huang, Ching-Jang; Chao, Pei-Min

    2008-02-01

    Bitter melon (Momordica charantia; BM) has been shown to ameliorate diet-induced obesity and insulin resistance. To examine the effect of BM supplementation on cell size and lipid metabolism in adipose tissues, three groups of rats were respectively fed a high-fat diet supplemented without (HF group) or with 5 % lyophilised BM powder (HFB group), or with 0.01 % thiazolidinedione (TZD) (HFT group). A group of rats fed a low-fat diet was also included as a normal control. Hyperinsulinaemia and glucose intolerance were observed in the HF group but not in HFT and HFB groups. Although the number of large adipocytes (>180 microm) of both the HFB and HFT groups was significantly lower than that of the HF group, the adipose tissue mass, TAG content and glycerol-3-phosphate dehydrogenase activity of the HFB group were significantly lower than those of the HFT group, implying that BM might reduce lipogenesis in adipose tissue. Experiment 2 was then conducted to examine the expression of lipogenic genes in adipose tissues of rats fed low-fat, HF or HFB diets. The HFB group showed significantly lower mRNA levels of fatty acid synthase, acetyl-CoA carboxylase-1, lipoprotein lipase and adipocyte fatty acid-binding protein than the HF group (P < 0.05). These results indicate BM can reduce insulin resistance as effective as the anti-diabetic drug TZD. Furthermore, BM can suppress the visceral fat accumulation and inhibit adipocyte hypertrophy, which may be associated with markedly down regulated expressions of lipogenic genes in the adipose. PMID:17651527

  17. Corn Gluten Hydrolysate Affects the Time-Course of Metabolic Changes Through Appetite Control in High-Fat Diet-Induced Obese Rats.

    Science.gov (United States)

    Lee, Hyojung; Lee, Hyo Jin; Kim, Ji Yeon; Kwon, Oran

    2015-12-01

    This study first investigated the effects of corn gluten hydrolysate (CGH) (1.5 g/day) administration for 7 days on appetite-responsive genes in lean Sprague-Dawley (SD) rats. In a second set of experiments, the metabolic changes occurring at multiple time points over 8 weeks in response to CGH (35.33% wt/wt) were observed in high-fat (HF, 60% of energy as fat) diet-fed SD rats. In lean rats, the hypothalamus neuropeptide-Y and proopiomelanocortin mRNA levels of the CGH group were significantly changed in response to CGH administration. In the second part of the study, CGH treatment was found to reduce body weight and perirenal and epididymal fat weight. CGH also prevented an increase in food intake at 2 weeks and lowered plasma leptin and insulin levels in comparison with the HF group. This reduction in the plasma and hepatic lipid levels was followed by improved insulin resistance, and the beneficial metabolic effects of CGH were also partly related to increases in plasma adiponectin levels. The Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), an index of insulin resistance, was markedly improved in the HF-CGH group compared with the HF group at 6 weeks. According to the microarray results, adipose tissue mRNA expression related to G-protein coupled receptor protein signaling pathway and sensory perception was significantly improved after 8 weeks of CGH administration. In conclusion, the present findings suggest that dietary CGH may be effective for improving hyperglycemia, dyslipidemia and insulin resistance in diet-induced obese rats as well as appetite control in lean rats. PMID:26549503

  18. Human monoclonal antibodies against glucagon receptor improve glucose homeostasis by suppression of hepatic glucose output in diet-induced obese mice.

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    Wook-Dong Kim

    Full Text Available AIM: Glucagon is an essential regulator of hepatic glucose production (HGP, which provides an alternative therapeutic target for managing type 2 diabetes with glucagon antagonists. We studied the effect of a novel human monoclonal antibody against glucagon receptor (GCGR, NPB112, on glucose homeostasis in diet-induced obese (DIO mice. METHODS: The glucose-lowering efficacy and safety of NPB112 were investigated in DIO mice with human GCGR for 11 weeks, and a hyperinsulinemic-euglycemic clamp study was conducted to measure HGP. RESULTS: Single intraperitoneal injection of NPB112 with 5 mg/kg effectively decreased blood glucose levels in DIO mice for 5 days. A significant reduction in blood glucose was observed in DIO mice treated with NPB112 at a dose ≥5 mg/kg for 6 weeks, and its glucose-lowering effect was dose-dependent. Long-term administration of NPB112 also caused a mild 29% elevation in glucagon level, which was returned to the normal range after discontinuation of treatment. The clamp study showed that DIO mice injected with NPB112 at 5 mg/kg were more insulin sensitive than control mice, indicating amelioration of insulin resistance by treatment with NPB112. DIO mice treated with NPB112 showed a significant improvement in the ability of insulin to suppress HGP, showing a 33% suppression (from 8.3 mg/kg/min to 5.6 mg/kg/min compared to the 2% suppression (from 9.8 mg/kg/min to 9.6 mg/kg/min in control mice. In addition, no hypoglycemia or adverse effect was observed during the treatment. CONCLUSIONS: A novel human monoclonal GCGR antibody, NPB112, effectively lowered the glucose level in diabetic animal models with mild and reversible hyperglucagonemia. Suppression of excess HGP with NPB112 may be a promising therapeutic modality for the treatment of type 2 diabetes.

  19. Dietary supplementation with phytosterol and ascorbic acid reduces body mass accumulation and alters food transit time in a diet-induced obesity mouse model

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    Kozlowski Petri

    2011-06-01

    Full Text Available Abstract Previous research indicates that animals fed a high fat (HF diet supplemented with disodium ascorbyl phytostanyl phosphate (DAPP exhibit reduced mass accumulation when compared to HF control. This compound is a water-soluble phytostanol ester and consists of a hydrophobic plant stanol covalently bonded to ascorbic acid (Vitamin C. To provide insight into the mechanism of this response, we examined the in vivo effects of a high fat diet supplemented with ascorbic acid (AA in the presence and absence of unesterified phytosterols (PS, and set out to establish whether the supplements have a synergistic effect in a diet-induced obesity mouse model. Our data indicate that HF diet supplementation with a combination of 1% w/w phytosterol and 1% w/w ascorbic acid results in reduced mass accumulation, with mean differences in absolute mass between PSAA and HF control of 10.05%; and differences in mass accumulation of 21.6% (i.e. the PSAA group gained on average 21% less mass each week from weeks 7-12 than the HF control group. In our previous study, the absolute mass difference between the 2% DAPP and HF control was 41%, while the mean difference in mass accumulation between the two groups for weeks 7-12 was 67.9%. Mass loss was not observed in animals supplemented with PS or AA alone. These data suggest that the supplements are synergistic with respect to mass accumulation, and the esterification of the compounds further potentiates the response. Our data also indicate that chronic administration of PS, both in the presence and absence of AA, results in changes to fecal output and food transit time, providing insight into the possibility of long-term changes in intestinal function related to PS supplementation.

  20. Diet induced thermogenesis

    OpenAIRE

    Westerterp KR

    2004-01-01

    Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Resu...

  1. Beneficial metabolic effects of CB1R anti-sense oligonucleotide treatment in diet-induced obese AKR/J mice.

    Directory of Open Access Journals (Sweden)

    Yuting Tang

    Full Text Available An increasing amount of evidence supports pleiotropic metabolic roles of the cannibinoid-1 receptor (CB1R in peripheral tissues such as adipose, liver, skeletal muscle and pancreas. To further understand the metabolic consequences of specific blockade of CB1R function in peripheral tissues, we performed a 10-week-study with an anti-sense oligonucleotide directed against the CB1R in diet-induced obese (DIO AKR/J mice. DIO AKR/J mice were treated with CB1R ASO Isis-414930 (6.25, 12.5 and 25 mg/kg/week or control ASO Isis-141923 (25 mg/kg/week via intraperitoneal injection for 10 weeks. At the end of the treatment, CB1R mRNA from the 25 mg/kg/week CB1R ASO group in the epididymal fat and kidney was decreased by 81% and 63%, respectively. Body weight gain was decreased in a dose-dependent fashion, significantly different in the 25 mg/kg/week CB1R ASO group (46.1±1.0 g vs veh, 51.2±0.9 g, p<0.05. Body fat mass was reduced in parallel with attenuated body weight gain. CB1R ASO treatment led to decreased fed glucose level (at week 8, 25 mg/kg/week group, 145±4 mg/dL vs veh, 195±10 mg/dL, p<0.05. Moreover, CB1R ASO treatment dose-dependently improved glucose excursion during an oral glucose tolerance test, whereas control ASO exerted no effect. Liver steatosis was also decreased upon CB1R ASO treatment. At the end of the study, plasma insulin and leptin levels were significantly reduced by 25 mg/kg/week CB1R ASO treatment. SREBP1 mRNA expression was decreased in both epididymal fat and liver. G6PC and fatty acid translocase/CD36 mRNA levels were also reduced in the liver. In summary, CB1R ASO treatment in DIO AKR/J mice led to improved insulin sensitivity and glucose homeostasis. The beneficial effects of CB1R ASO treatment strongly support the notion that selective inhibition of the peripheral CB1R, without blockade of central CB1R, may serve as an effective approach for treating type II diabetes, obesity and the metabolic syndrome.

  2. Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice

    Directory of Open Access Journals (Sweden)

    Altintas Mehmet M

    2011-11-01

    Full Text Available Abstract Background Obesity is characterized by increased cell death and inflammatory reactions in the adipose tissue. Here, we explored pathophysiological alterations taking place in the adipose tissue in long-standing obesity. In the epididymal fat of C57BL/6 mice fed a high-fat diet for 20 weeks, the prevalence and distribution of dead adipocytes (crown-like structures, mast cells (toluidine blue, mMCP6, macrophages (F4/80, and apoptotic cells (cleaved caspase-3 were measured. Moreover, gene and/or protein expression of several adipocytokines (leptin, adiponectin, TNF-α, IL-10, IL-6, MCP-1, F4/80, mMCP6, cleaved caspase-3 were determined. Results We observed that the epididymal fat mass was lower in obese than in lean mice. In obese mice, the epididymal fat mass correlated inversely with body weight and liver mass. Dead adipocytes, mast cells, macrophages, and apoptotic cells were abundant in the epididymal fat of obese mice, especially in the rostral vs. caudal zone. Accordingly, mMCP6, F4/80, and cleaved caspase-3 gene and/or protein expression was increased. Conversely, adiponectin, leptin, IL-6, and MCP-1 gene expression levels were lower in the epididymal fat of obese than lean mice. Although TNF-α and IL-10 gene expression was higher in the epididymal fat of obese mice, their expression relative to F4/80 and mMCP6 expression were lower in the heavily infiltrated rostral than caudal zone. Conclusions This study demonstrates that in mice with long-standing obesity diminished gene expression of several adipocytokines accompany apoptosis and reduced mass of the epididymal fat. Our findings suggest that this is due to both increased prevalence of dead adipocytes and altered immune cell activity. Differential distribution of metabolically challenged adipocytes is indicative of the presence of biologically diverse zones within the epididymal fat.

  3. 饮食诱导小鼠肥胖疾病模型的建立%Establishment of A Mouse Model of Diet-induced Obesity

    Institute of Scientific and Technical Information of China (English)

    胡晓东; 李鸿炎

    2012-01-01

    目的 建立适合的食源性肥胖症动物疾病模型,用于评价减肥药物临床前动物实验的有效性和安全性.方法 将120只C57BL/6J小鼠按随机数字表法分为2组,模型组(n=110)采用高脂饲养饮食诱导肥胖(DIO),对照组(n=10)采用标准饲料饲养,2组均饲养12周.每周监测小鼠体质量和摄食量的变化,ELISA法检测血浆中血糖、血脂和胰岛素水平,断尾采血进行糖耐量(OGTT)试验.结果 饲养12周后,模型组和对照组小鼠体质量分别为(36.90±5.07)、(27.68±2.27)g,2组比较差异有统计学意义(P<0.001);模型组有80.9%的小鼠发育为DIO;模型组较对照组摄食量明显增加(P<0.01).与对照-OGTT组相比,DIO-OGTT组血糖和胰岛素明显增加(P<0.01),并伴有糖耐量减低和高脂血症.结论 饮食诱导可成功建立小鼠肥胖疾病模型,高脂饮食可以导致具有肥胖倾向的小鼠体质量增加,此模型与临床肥胖症病理接近,且具有稳定性好、操作简单、费用低等优点.%Objective To establish an animal model of diet-induced obesity (DIO),and to investigate the efficacy and safety of weight-loss drugs in pre-clinical animal testing. Methods A total of 120 C57BL/6J mice were randomly divided into fed high-fat diet (Research Diets Inc. , D12492,60%kcal% fat;DIO group, n = 110) or standard chow (control group, n= 10) for 12 weeks. Food intake and body weight were measured weekly. The levels of plasma glucose,insulin and lipid were detected by enzyme-linked immunosorbent assay(ELISA). Blood samples were collected by tail cutting for glucose tolerance test. Results After feeding for 12 weeks, 80. 9% of mice in DIO group developed obesity and had impaired glucose tolerance, and hyperlipidemia. Compared with control group,body weight was significantly increased in DIO group [(36. 90±5. 07)g vs (27. 68 ± 2. 27)g,P<0. 001]. Moreover,food intake and levels of plasma glucose and insulin obviously elevated compared with

  4. Lemon Polyphenols Suppress Diet-induced Obesity by Up-Regulation of mRNA Levels of the Enzymes Involved in β-Oxidation in Mouse White Adipose Tissue

    OpenAIRE

    Fukuchi, Yoshiko; Hiramitsu, Masanori; Okada, Miki; Hayashi, Sanae; Nabeno, Yuka; Osawa, Toshihiko; Naito, Michitaka

    2008-01-01

    The aim of this study was to investigate the effect of dietary lemon polyphenols on high-fat diet-induced obesity in mice, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. Mice were divided into three groups and fed either a low fat diet (LF) or a high fat diet (HF) or a high fat diet supplemented with 0.5% w/w lemon polyphenols (LP) extracted from lemon peel for 12 weeks. Body weight gain, fat pad accumulation, the development of ...

  5. Blockade of tumor necrosis factor (TNF) receptor type 1-mediated TNF-alpha signaling protected Wistar rats from diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Liang, Huifang; Yin, Bingjiao; Zhang, Hailong; Zhang, Shu; Zeng, Qingling; Wang, Jing; Jiang, Xiaodan; Yuan, Li; Wang, Cong-Yi; Li, Zhuoya

    2008-06-01

    TNF-alpha plays an important role in the pathogenesis of obesity and insulin resistance in which the effect of TNF-alpha signaling via TNF receptor type 1 (TNFR1) largely remains controversial. To delineate the role of TNFR1-mediated TNF-alpha signaling in the pathogenesis of this disorder, a TNFR1 blocking peptide-Fc fusion protein (TNFR1BP-Fc) was used for the present study. Wistar rats were fed a high-fat/high-sucrose (HFS) diet for 16 wk until obesity and insulin resistance developed. In comparison with increased body weight and fat weight, enlarged adipocytes, and hypertriglyceridemia in the obese state, the subsequent 4-wk treatment with TNFR1BP-Fc resulted in significant weight loss characterized by decreased fat pad weight and adipocyte size and reduced plasma triglycerides. Furthermore, obesity-induced insulin resistance, including hyperinsulinemia, elevated C-peptide, higher degree of hyperglycemia after glucose challenge, and less hypoglycemic response to insulin, was markedly improved, and the compensatory hyperplasia and hypertrophy of pancreatic islets were reduced. Interestingly, treatment with TNFR1BP-Fc markedly suppressed systemic TNF-alpha release and its local expression in pancreatic islets and muscle and adipose tissues. In addition, blockage of TNFR1-mediated TNF-alpha signaling in obese rats significantly enhanced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in the muscle and fat tissues. Our results strongly suggest a pivotal role for TNFR1-mediated TNF-alpha signaling in the pathogenesis of obesity and insulin resistance. Thus, TNFR1BP-Fc may be a good candidate for the treatment of this disease. PMID:18339717

  6. Göttingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals

    DEFF Research Database (Denmark)

    Ludvigsen, Trine Pagh; Kirk, Rikke Kaae; Christoffersen, Berit Østergaard;

    2015-01-01

    in human patients, inclusion of this disease aspect in the characterization of a such model, is highly relevant. The objective of this study was to evaluate the effect of mild streptozotocin-induced diabetes on ex- and in vivo end-points in a diet-induced atherosclerotic minipig model. Castrated male...... Göttingen minipigs were fed standard chow (CD), atherogenic diet alone (HFD) or with superimposed mild streptozotocin-induced diabetes (HFD-D). Circulating markers of inflammation (C-reactive protein (CRP), oxidized low-density lipoprotein (oxLDL), plasminogen activator inhibitor-1, lipid and glucose......From a pharmacological perspective, readily-available, well-characterized animal models of cardiovascular disease, including relevant in vivo markers of atherosclerosis are important for evaluation of novel drug candidates. Furthermore, considering the impact of diabetes mellitus on atherosclerosis...

  7. THE DIFFERENTIAL SCREENING OF SERUM PROTEINS IN DIET-INDUCED OBESE AND OBESE-RESISTANT RATS%饮食诱导肥胖与肥胖抵抗大鼠血清差异蛋白筛选

    Institute of Scientific and Technical Information of China (English)

    赵丹; 麻微微; 王舒然

    2006-01-01

    目的:探讨高脂饲料诱导的肥胖(diet-induced obesity,DIO)与肥胖抵抗(diet-induced obesity resistance,DIO-R)大鼠不同易感性的差异及血清中蛋白表达.方法:健康雄性SD大鼠40只,随机分为基础组和高脂饲料组,分别给予基础饲料和高脂饲料5w后,参照Levin等的方法建立动物模型,按照体重增加量排序,位于体重上1/3的大鼠筛选为肥胖大鼠,位于体重下1/3的大鼠筛选为肥胖抵抗大鼠.处死动物,收集血清样品检测各组相关指标的差异,并应用SELDI蛋白质芯片技术检测DIO与DIO-R大鼠血清蛋白的差异表达.结果:DIO大鼠体重﹑体脂比﹑血糖﹑血脂均与DIO-R大鼠有显著性差异.由蛋白质芯片检测图可见,在分子量2~100 ku范围内,分子量为7 945和9 513的蛋白峰在DIO大鼠和DIO-R大鼠血清中存在差异;分子量为6256、6267、4496的蛋白峰在DIO-R大鼠和基础组大鼠血清中存在差异.结论:SD大鼠对高脂饮食诱导的DIO和DIO-R存在易感性差异,应用SELDI蛋白质芯片技术筛选出了DIO大鼠与DIO-R大鼠血清差异蛋白,为以后进行蛋白质分离﹑纯化及鉴定提供依据.

  8. Long-term characterization of the diet-induced obese and diet-resistant rat model

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel;

    2010-01-01

    effectively reduced food intake and body weight in DIO rats. Liraglutide furthermore improved glucose tolerance when compared with sibutramine. Our data highlights the usefulness of a polygenetic animal model for screening of compounds affecting food intake, body weight, and glucose homeostasis. Furthermore...

  9. Obesidade induzida por consumo de dieta: modelo em roedores para o estudo dos distúrbios relacionados com a obesidade Diet-induced obesity: rodent model for the study of obesity-related disorders

    Directory of Open Access Journals (Sweden)

    Tiago Campos Rosini

    2012-06-01

    mostly to genetic mutations, but this model is far from that found in humans. The use of hypercaloric or hyperlipidemic diets has been used as a model of obesity induction in animals, because of its similarity to the genesis and metabolic responses caused by obesity in humans. The objective of this review is to show the different types of diets used to induce obesity in rodents, the induced metabolic alterations, and to identify some points that should be taken into account so that the model can be effective for the study of obesity-related complications. A search was performed in the PubMed database using the following keywords: 1- "hypercaloric diet" AND "rodent", 2- "hyperlipidic diet" AND "rodent", selecting those considered the most relevant according to the following criteria: date of publication (1995-2011; the use of wild-type animals; detailed description of the diet used and analysis of biochemical and vascular parameters of interest. References were included to introduce subjects such as the increased prevalence of obesity and questions related to the genesis of obesity in humans. The model of diet-induced obesity in rodents can be considered effective when the objective is the study of the physiopathology of metabolic and vascular complications associated with obesity.

  10. Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats

    Science.gov (United States)

    Adam, Clare L.; Gratz, Silvia W.; Peinado, Diana I.; Thomson, Lynn M.; Garden, Karen E.; Williams, Patricia A.; Richardson, Anthony J.; Ross, Alexander W.

    2016-01-01

    Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity. PMID:27224646

  11. 低氧和运动对营养性肥胖大鼠血脂代谢的影响%Effect of Hypoxia and Exercise on Blood Lipid Metabolism of Diet-induced Obese Rats

    Institute of Scientific and Technical Information of China (English)

    邱烈峰

    2013-01-01

      采用高脂饲料饲喂健康 SPF 级雄性 SD 大鼠建立营养性肥胖模型,对肥胖大鼠进行4周的低氧和/或运动干预。结果表明,低氧、运动以及低氧复合运动均可改善营养性肥胖大鼠血脂代谢。其中低氧复合运动改善血脂代谢效果优于单纯低氧和单纯运动。%To investigate the effect of hypoxia and /or exercise intervention on blood lipid metabolism of diet -in-duced obese rats, SPF-grade healthly male Sprague-Dawley rats were fed high fat forage to establish the obese model . Then the obese model were subjected to hypoxia exposure in normobaric hypoxic tent simulating and /or exercise on a motor-driven rodent treadmill for 4 weeks.Results showed that the combined effects of hypoxia and exercise is more ef -fective than only hypoxia or only exercise in improving blood lipid metabolism in diet -induced obese rats.

  12. The Hypolipidemic Effect of Total Saponins from Kuding Tea in High-Fat Diet-Induced Hyperlipidemic Mice and Its Composition Characterized by UPLC-QTOF-MS/MS.

    Science.gov (United States)

    Song, Chengwu; Yu, Qingsong; Li, Xiaohua; Jin, Shuna; Li, Sen; Zhang, Yang; Jia, Shuailong; Chen, Cheng; Xiang, Yi; Jiang, Hongliang

    2016-05-01

    Kuding tea are used as a traditional tea material and widely consumed in China. In this study, total saponins (TS) from water extract of Kuding tea was prepared by D101 macroporous resins and analyzed by UPLC-QTOF-MS/MS. Then the hypolipidemic effect of TS extract was investigated in high-fat diet-induced hyperlipidemic mice. For comprehensive identification or characterization of saponins in TS extract, 3 major saponins of Kudinoside A, Kudinoside F, and Kudinoside D were isolated and used as standards to investigate the MS/MS fragmentation pattern. As a result, 52 saponins were identified or characterized in TS extract from Kuding tea. In addition, the increased levels of mice serum TC, LDL-C, HDL-C, and atherogenic index (AI) were significantly reduced after the treatment of TS extract. Also, the liver protective effect of TS extract was obviously judged from the photographs stained with oil red-O staining. Meanwhile, TS extract significantly upregulated the expression of hepatic scavenger receptors including SR-AI, SR-BI, and CD36. Therefore, it is reasonable to assume that the overexpression of hepatic scavenger receptors was involved in the hypolipidemic effect of Kuding tea on the high-fat diet-induced hyperlipidemic mice. The TS extract could influence these scavenger receptors, and this could be the potential mechanism of TS extract from Kuding tea in the treatment of lipid disorders. These results give the evidence that the saponins in Kuding tea could provide benefits in managing hypercholesterolemia and may be a good candidate for development as a functional food and nutraceutical. PMID:27074384

  13. Diet-Induced Obesity in mice is associated with hyperinsulinemia, hepatic steatosis, and glomerulopathy in C57Bl/6J mice

    OpenAIRE

    Hoffler, Undi; Hobbie, Kristen; Wilson, Ralph; Bai, Re; Rahman, Akef; Malarkey, David; Travlos, Greg; Ghanayem, Burhan I.

    2009-01-01

    The prevalence and increasing incidences of obesity and obesity-related illnesses are not limited to westernized countries, but exist as a global epidemic impacting the health of adults and children. According to the WHO, over 1 billion adults are overweight (BMI > 25 kg/m2) and approximately one-third of this population has been diagnosed as clinically obese (BMI > 30 kg/m2). Causality between obesity and metabolic disorders (such as type 2 diabetes), cancer, cardiovascular diseases and live...

  14. Theaflavin Synthesized in a Selective, Domino-Type, One-Pot Enzymatic Biotransformation Method with Camellia sinensis Cell Culture Inhibits Weight Gain and Fat Accumulation to High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Takemoto, Masumi; Takemoto, Hiroaki; Saijo, Ryoyasu

    2016-08-01

    The polyphenolic compound theaflavin, which is the main red pigment present in black tea, is reported to elicit various physiological effects. Because of the extremely low concentration of theaflavin present in black tea, its extraction from black tea leaves in quantities sufficient for use in medical studies has been difficult. We have developed a simple, inexpensive, selective, domino-type, one-pot enzymatic biotransformation method for the synthesis of theaflavin that is suitable for use in medical studies. Subsequent administration of this synthetic theaflavin to high-fat diet-induced obese mice inhibited both body weight gain and visceral fat accumulation, with no significant difference in the amount of faeces between the experimental and control mice. PMID:27237789

  15. Fermented Rhizoma Atractylodis Macrocephalae alleviates high fat diet-induced obesity in association with regulation of intestinal permeability and microbiota in rats

    OpenAIRE

    Wang, Jing-hua; Bose, Shambhunath; Kim, Hyung-Gu; Han, Kyung-Sun; Kim, Hojun

    2015-01-01

    Accumulating evidence suggests the anti-inflammatory and anti-obesity activities of Rhizoma Atractylodis Macrocephalae (RAM). Here, we evaluated the anti-obesity impact of unfermented (URAM) versus fermented RAM (FRAM) using both in vitro and in vivo models. Both URAM and FRAM exhibited marked anti-inflammatory, anti-adipogenic, and anti-obesity activities, and modulation of the gut microbial distribution. However, FRAM, compared to URAM, resulted in more efficient suppression of NO productio...

  16. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

    OpenAIRE

    Najla Gooda Sahib Jambocus; Nazamid Saari; Amin Ismail; Alfi Khatib; Mohamad Fawzi Mahomoodally; Azizah Abdul Hamid

    2015-01-01

    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. le...

  17. Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance

    OpenAIRE

    Liew, Chong Wee; Boucher, Jeremie; Cheong, Jit Kong; Vernochet, Cecile; Koh, Ho-Jin; Mallol, Cristina; Townsend, Kristy; Langin, Dominique; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Hellerstein, Marc K.; Farmer, Stephen R.; Goodyear, Laurie; Doria, Alessandro

    2012-01-01

    SUMMARY Obesity develops due to altered energy homeostasis favoring fat storage. Here we describe a novel transcription co-regulator for adiposity and energy metabolism, TRIP-Br2 (also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of the knockout (KO) mice exhibited greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The KOs also exhibit higher ene...

  18. Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance

    OpenAIRE

    Liew, Chong Wee; Boucher, Jeremie; Cheong, Jit Kong; Vernochet, Cecile; Koh, Ho-Jin; Mallol, Cristina; Townsend, Kristy; Langin, Dominique; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Hellerstein, Marc K.; Farmer, Stephen R.; Goodyear, Laurie; Doria, Alessandro

    2013-01-01

    SUMMARY Obesity develops due to altered energy homeostasis favoring fat storage. Here we describe a novel transcription co-regulator for adiposity and energy metabolism, TRIP-Br2 (also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of the knockout (KO) mice exhibited greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The KOs also exhibit higher ene...

  19. Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα.

    Science.gov (United States)

    Zhang, Yanan; Song, Chengwei; Li, Haiou; Hou, Jingdong; Li, Dongliang

    2016-06-01

    Obesity is a risk factor for several pain syndromes and is associated with increased pain sensitivity. Evidence suggests that obesity causes the downregulation of peroxisome proliferator‑activated receptor (PPAR)α in the spinal cord, contributing to augmented peripheral edema and inflammatory hyperalgesia. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, has been shown to upregulate PPARα in the peripheral tissues of obese animals. The present study hypothesized that UA prevents augmented peripheral inflammation and inflammatory hyperalgesia in obesity by restoring downregulated spinal PPARα. The present study demonstrated that Sprague‑Dawley rats fed a high‑fat diet (HFD) for 12 weeks developed obesity and metabolic disorder. Following carrageenan injection, the HFD rats exhibited increased thermal hyperalgesia and paw edema, compared with the rats fed a low‑fat diet. Molecular investigations revealed that the HFD rats exhibited decreased PPARα activity, and exaggerated expression of inflammatory mediators and nuclear factor‑kB activity in the spinal cord in response to carrageenan. Oral administration of UA ameliorated obesity and metabolic disorder, and prevented increased thermal hyperalgesia and paw edema in the HFD rats. Additionally, UA normalized PPARα activity and inhibited the exaggerated spinal cord inflammatory response to carrageenan. Although the knockdown of spinal PPARα with small interfering RNA following the administration of UA did not alter obesity or metabolic parameters, it eradicated the beneficial effects of UA on thermal hyperalgesia and paw edema, and reversed the spinal cord inflammatory response. These results suggested that the systemic administration of UA inhibited the exaggerated spinal cord inflammatory response to peripheral inflammatory stimulation in HFD‑induced obesity by restoring downregulated spinal PPARα, preventing peripheral inflammation and inflammatory hyperalgesia. UA may be a

  20. Consequences of a diet-induced obesity on the plasticity of the Pancreatic Intrinsic Nervous System and the nervous control of pancreatic endocrine secretion in young mice

    OpenAIRE

    Blat, Sophie; Saade, Marie-Béatrice; Moriez, RAPHAEL; Aubert, Philippe; Neunlist, Michel

    2012-01-01

    Objective Pancreatic Intrinsic Nervous System (PINS) is involved in the control of pulsatility and amplitude of insulin secretion (IS) both altered in obese and type 2 diabetic patients. However, little is known about the role of the PINS during obesity and in the genesis of pancreatic endocrine dysfunctions. The aim of our study was to determine the impact of obesity upon the PINS and its functional consequences upon IS in young mice. Methods C57BL/6J mice aged 4 weeks received either a norm...

  1. Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

    OpenAIRE

    Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

    2012-01-01

    Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates in...

  2. High-Fat Diet-Induced Neuropathy of Prediabetes and Obesity: Effect of PMI-5011, an Ethanolic Extract of Artemisia dracunculus L.

    OpenAIRE

    Pierre Watcho; Roman Stavniichuk; David M. Ribnicky; Ilya Raskin; Obrosova, Irina G.

    2010-01-01

    Artemisia species are a rich source of herbal remedies with antioxidant and anti-inflammatory properties. We evaluated PMI-5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-sfat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system. C57Bl6/J mice fed high-fat diet for 16 weeks developed obesity, moderate nonfasting hyperglycemia, nerve conduction deficit, thermal and mechanical hypoalg...

  3. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats

    OpenAIRE

    María Miana; María Galán; Ernesto Martínez-Martínez; Saray Varona; Raquel Jurado-López; Belén Bausa-Miranda; Alfonso Antequera; María Luaces; José Martínez-González; Cristina Rodríguez; Victoria Cachofeiro

    2015-01-01

    ABSTRACT Extracellular matrix (ECM) remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expressi...

  4. Effect of short-term hyperglycemia on adipose tissue fluxes of selected cytokines in vivo during multiple phases of diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Siklova, Michaela; Simonsen, Lene; Polak, Jan; Stich, Vladimir; Bülow, Jens

    2015-01-01

    CONTEXT: Hyperglycemia is suggested to be one of the drivers of the proinflammatory state observed in obese and diabetic patients. OBJECTIVES: The objectives of the study was to investigate whether sc abdominal adipose tissue (scAT) could be one of the important sources of proinflammatory cytokin....... This lowered responsiveness of the inflammation-related system may be an important feature of the weight reduction-induced improvement of the metabolic status of obese prediabetic individuals....

  5. Left ventricular mechanical dysfunction in diet-induced obese mice is exacerbated during inotropic stress: a cine DENSE cardiovascular magnetic resonance study

    OpenAIRE

    Haggerty, Christopher M.; Mattingly, Andrea C.; Kramer, Sage P.; Binkley, Cassi M.; Jing, Linyuan; Suever, Jonathan D.; Powell, David K.; Charnigo, Richard J; Epstein, Frederick H.; Fornwalt, Brandon K

    2015-01-01

    Background Obesity is a risk factor for cardiovascular disease. There is evidence of impaired left ventricular (LV) function associated with obesity, which may relate to cardiovascular mortality, but some studies have reported no dysfunction. Ventricular function data are generally acquired under resting conditions, which could mask subtle differences and potentially contribute to these contradictory findings. Furthermore, abnormal ventricular mechanics (strains, strain rates, and torsion) ma...

  6. Differential expression of dopamine D2 and D4 receptor and tyrosine hydroxylase mRNA in mice prone, or resistant, to chronic high-fat diet-induced obesity.

    Science.gov (United States)

    Huang, Xu-Feng; Yu, Yinghua; Zavitsanou, Katerina; Han, Mei; Storlien, Len

    2005-04-27

    The present study examined brain dopamine D2 and D4 receptor and tyrosine hydroxylase (TH) mRNA expression in chronic high-fat diet-induced obese (cDIO) and obese-resistant (cDR) mice. Twenty-eight mice were fed a high-fat diet (HF: 40% of calories from fat) for 6 weeks and then classified as cDIO (n = 8) or cDR (n = 8) mice according to the highest and lowest body weight gainers, respectively. Seven mice were fed a low-fat diet (LF: 10% of calories from fat) and used as controls. After 20 weeks of feeding, visceral fat per gram of initial body weight was significantly higher in the cDIO group (ratio: 0.25, 0.09, and 0.04; P cDIO vs. cDR and LF, respectively). Using quantitative in situ hybridization techniques, the levels of D2 and D4 receptor and tyrosine hydroxylase (TH) mRNAs were measured in multiple brain sections. The cDIO mice had a significantly higher level of D2 receptor mRNA expression in the core of the nucleus accumbens (AcbC, +16%) and ventral parts of caudate putamen (CPu, 21% and 24%) compared to the cDR and LF mice. The levels of D2 receptor mRNA expression in the AcbC and ventromedial part of the CPu were positively related to the final body weight. This study is the first to systematically examine the D4 mRNA expression in the mouse brain using in situ hybridization method. D4 receptor mRNA expression in the ventromedial hypothalamic nucleus (VMH) and the ventral part of the lateral septal nucleus were also significantly higher in the cDIO mice compared to the cDR and LF mice (+31% and +60%; P cDIO mice compared to cDR mice. In conclusion, this study has demonstrated differentially regulated levels of D2 and D4 receptor and TH mRNA expression in specific brain regions of cDIO and cDR mice. It provides evidence that D4 receptors may play an important role influencing satiety via the mesohypothalamic pathway while the D2 receptor may regulate reward and motor centers via mesolimbic and nigrostriatal pathways. These findings contribute to the

  7. Pre-clinical evolutionary study of Clerodendrum phlomidis as an anti-obesity agent against high fat diet induced C57BL/6J mice

    Institute of Scientific and Technical Information of China (English)

    Vijay R Chidrawar; Krishnakant N Patel; Havagiray R Chitme; Shruti S Shiromwar

    2012-01-01

    Objective: Anti-obesity activity of alcoholic and methanolic extracts of roots of Clerodendrumphlomidis was evaluated against high fat diet (HFD) induced obesity in C57BL/6J female mice. Methods: Obesity was induced by feeding high fat diet for 13 weeks to C57BL/6J female mice and one group was kept on normal chow diet in order to evaluate the effect of Clerodendrumphlomidis on food intake, body weight changes, digestive enzyme activity, lipid metabolism, theromogenesis, adiposities diameter and histology of fat pad. Results: Among these two extracts methanolic extract of Clerodendrum phlomidis (MECP) have shown strong anti-obesity effect compare to alcoholic extract of Clerodendrum phlomidis (AECP). LD50 value was found to be more than 2000 mg/kg. Conclusions: MECP have shown more promising effects than AECP may be because of its multiple mechanisms. Anti-obesity activity produced by MECP is because of inhibition of pancreatic lipase activity which delays the intestinal absorption of dietary fat. Inhibition of pancreatic lipase activity was confirmed by in-vitro studies. MECP also containsβ-sitosterol in abundant amount which was confirmed by HPTLC analysis. Moreover flavonoid content in the plant has anorexic property. By this study we concluded that MECP is beneficial for the suppression of obesity and associated complications like T2DM.

  8. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats.

    Science.gov (United States)

    Miana, María; Galán, María; Martínez-Martínez, Ernesto; Varona, Saray; Jurado-López, Raquel; Bausa-Miranda, Belén; Antequera, Alfonso; Luaces, María; Martínez-González, José; Rodríguez, Cristina; Cachofeiro, Victoria

    2015-06-01

    Extracellular matrix (ECM) remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD). Interestingly, treatment with β-aminopropionitrile (BAPN), a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters - it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA) index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4), as well as the increase in suppressor of cytokine signaling 3 (SOCS3) and dipeptidyl peptidase 4 (DPP4) levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX activity for

  9. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats

    Directory of Open Access Journals (Sweden)

    María Miana

    2015-06-01

    Full Text Available Extracellular matrix (ECM remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX family of amine oxidases, including LOX and LOX-like (LOXL isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD. Interestingly, treatment with β-aminopropionitrile (BAPN, a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters – it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4, as well as the increase in suppressor of cytokine signaling 3 (SOCS3 and dipeptidyl peptidase 4 (DPP4 levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX

  10. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

    Directory of Open Access Journals (Sweden)

    Najla Gooda Sahib Jambocus

    2016-01-01

    Full Text Available The prevalence of obesity is increasing worldwide, with high fat diet (HFD as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60. After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a 1H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate, amino acid metabolism (alanine, 2-hydroxybutyrate, choline metabolism (betaine, creatinine metabolism (creatinine, and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline. Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment.

  11. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

    Science.gov (United States)

    Gooda Sahib Jambocus, Najla; Saari, Nazamid; Ismail, Amin; Mahomoodally, Mohamad Fawzi; Abdul Hamid, Azizah

    2016-01-01

    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a 1H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment. PMID:26798649

  12. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a (1)H NMR Metabolomics Approach.

    Science.gov (United States)

    Gooda Sahib Jambocus, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Mohamad Fawzi; Abdul Hamid, Azizah

    2016-01-01

    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment. PMID:26798649

  13. Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    Young-Sil Lee; Bong-Keun Choi; Hae Jin Lee; Dong-Ryung Lee; Jinhua Cheng; Won-Keun Lee; Seung Hwan Yang; Joo-Won Suh

    2015-01-01

    Objective: To explore the anti-obesity effects and the mechanism of action of Monascus pilosus (M. pilosus)-fermented black soybean (MFBS) extracts (MFBSE) and MFBS powders (MFBSP) in adipocytes and high-fat diet (HFD)-induced obese mice, respectively. Methods:Black soybean was fermented with M. pilosus, and the main constituents in MFBS were analyzed by HPLC analysis. In vitro, MFBSE were examined for anti-adipogenic effects using Oil-Red O staining. In vivo, mice were fed a normal-fat diet (NFD) control, HFD control or HFD containing 1 g/kg MFBSP for 12 weeks, and then body weight gain and tissues weight measured. Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects. Results: MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity. MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice. MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes, such as peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS), in adipocytes and in white adipose tissue (WAT) of HFD-induced obese mice. Conclusions: These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFD-induced obese mice.

  14. Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Liew, Chong Wee; Boucher, Jeremie; Cheong, Jit Kong; Vernochet, Cecile; Koh, Ho-Jin; Mallol, Cristina; Townsend, Kristy; Langin, Dominique; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Hellerstein, Marc K; Farmer, Stephen R; Goodyear, Laurie; Doria, Alessandro; Blüher, Matthias; Hsu, Stephen I-Hong; Kulkarni, Rohit N

    2013-02-01

    Obesity develops as a result of altered energy homeostasis favoring fat storage. Here we describe a new transcription co-regulator for adiposity and energy metabolism, SERTA domain containing 2 (TRIP-Br2, also called SERTAD2). TRIP-Br2-null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of these knockout mice showed greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The knockout mice also have higher energy expenditure because of increased adipocyte thermogenesis and oxidative metabolism caused by upregulating key enzymes in their respective processes. Our data show that a cell-cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data, together with the observation that TRIP-Br2 expression is selectively elevated in visceral fat in obese humans, suggests that this transcriptional co-regulator is a new therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia. PMID:23291629

  15. Piperidine alkaloids from Piper retrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase.

    Science.gov (United States)

    Kim, Kyung Jin; Lee, Myoung-Su; Jo, Keunae; Hwang, Jae-Kwan

    2011-07-22

    The fruits of Piper retrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor δ (PPARδ) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPARδ protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300mg/kg/day for 8weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. Consistent with the in vitro results, PRPA activated AMPK signaling and altered the expression of lipid metabolism-related proteins in liver and skeletal muscle. Taken together, these findings demonstrate that PRPAs attenuate HFD-induced obesity by activating AMPK and PPARδ, and regulate lipid metabolism, suggesting their potential anti-obesity effects. PMID:21741367

  16. Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.

    Science.gov (United States)

    Wang, Shudong; Luo, Manyu; Zhang, Zhiguo; Gu, Junlian; Chen, Jing; Payne, Kristen McClung; Tan, Yi; Wang, Yuehui; Yin, Xia; Zhang, Xiang; Liu, Gilbert C; Wintergerst, Kupper; Liu, Quan; Zheng, Yang; Cai, Lu

    2016-09-01

    Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities: deficiency (ZD, 10mg zinc per 4057kcal), normal (ZN, 30mg zinc per 4057kcal) or supplement (ZS, 90mg zinc per 4057kcal). HFD induced a time-dependent obesity and ORCH, which was accompanied by increased cardiac inflammation and p38 MAPK activation. These effects were worsened by ZD in HFD/ZD mice and attenuated by ZS in HFD/ZS group, respectively. Also, administration of a p38 MAPK specific inhibitor in HFD mice for 3 months did not affect HFD-induced obesity, but completely abolished HFD-induced, and zinc deficiency-worsened, ORCH and cardiac inflammation. In vitro exposure of adult cardiomyocytes to palmitate induced cell hypertrophy accompanied by increased p38 MAPK activation, which was heightened by zinc depletion with its chelator TPEN. Inhibition of p38 MAPK with its specific siRNA also prevented the effects of palmitate on cardiomyocytes. These findings demonstrate that ZS alleviates but ZD heightens cardiac hypertrophy in HFD-induced obese mice through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways. PMID:27346292

  17. Chronic Treatment With a Melanocortin-4 Receptor Agonist Causes Weight Loss, Reduces Insulin Resistance, and Improves Cardiovascular Function in Diet-Induced Obese Rhesus Macaques

    OpenAIRE

    Kievit, Paul; Halem, Heather; Marks, Daniel L.; Dong, Jesse Z.; Glavas, Maria M.; Sinnayah, Puspha; Pranger, Lindsay; Cowley, Michael A.; Kevin L. Grove; Culler, Michael D.

    2013-01-01

    The melanocortin-4 receptor (MC4R) is well recognized as an important mediator of body weight homeostasis. Activation of MC4R causes dramatic weight loss in rodent models, and mutations in human are associated with obesity. This makes MC4R a logical target for pharmacological therapy for the treatment of obesity. However, previous studies in rodents and humans have observed a broad array of side effects caused by acute treatment with MC4R agonists, including increased heart rate and blood pre...

  18. The effect of exercise on expression of myokine and angiogenesis mRNA in skeletal muscle of high fat diet induced obese rat

    OpenAIRE

    Shin, Ki Ok; Bae, Ju Yong; Woo, Jinhee; Jang, Ki Soeng; Kim, Keun Su; Park, Jung Sub; Kim, In Ki; Kang, Sunghwun

    2015-01-01

    [Purpose] The purpose of this study was to investigate the effect of regular treadmill exercise on the mRNA expressions of myokines and angiogenesis factors in the skeletal muscle of obese rats. [Methods] Thirty two male Sprague-Dawley rats (4weeks old) were divided into the CO (control) and HF (high fat diet) groups. Obesity was induced in the HF group by consumption of 45% high-fat diet for 15 weeks. These groups were further subdivided into training groups (COT and HFT); the training group...

  19. Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice

    OpenAIRE

    Kim, Misung; Na, Woori; Sohn, Cheongmin

    2013-01-01

    Several reports suggest that obesity is a risk factor for osteoporosis. Vitamin K plays an important role in improving bone metabolism. This study examined the effects of vitamin K1 and vitamin K2 supplementation on the biochemical markers of bone turnover and morphological microstructure of the bones by using an obese mouse model. Four-week-old C57BL/6J male mice were fed a 10% fat normal diet group or a 45% kcal high-fat diet group, with or without 200 mg/1000 g vitamin K1 (Normal diet + K1...

  20. Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Jung, Un Ju; Cho, Yun-Young; Choi, Myung-Sook

    2016-01-01

    Several in vitro and in vivo studies have reported the anti-inflammatory, anti-diabetic and anti-obesity effects of the flavonoid apigenin. However, the long-term supplementary effects of low-dose apigenin on obesity are unclear. Therefore, we investigated the protective effects of apigenin against obesity and related metabolic disturbances by exploring the metabolic and transcriptional responses in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed an HFD or apigenin (0.005%, w/w)-supplemented HFD for 16 weeks. In HFD-fed mice, apigenin lowered plasma levels of free fatty acid, total cholesterol, apolipoprotein B and hepatic dysfunction markers and ameliorated hepatic steatosis and hepatomegaly, without altering food intake and adiposity. These effects were partly attributed to upregulated expression of genes regulating fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, electron transport chain and cholesterol homeostasis, downregulated expression of lipolytic and lipogenic genes and decreased activities of enzymes responsible for triglyceride and cholesterol ester synthesis in the liver. Moreover, apigenin lowered plasma levels of pro-inflammatory mediators and fasting blood glucose. The anti-hyperglycemic effect of apigenin appeared to be related to decreased insulin resistance, hyperinsulinemia and hepatic gluconeogenic enzymes activities. Thus, apigenin can ameliorate HFD-induced comorbidities via metabolic and transcriptional modulations in the liver. PMID:27213439

  1. Cafeteria diet induces obesity and insulin resistance associated with oxidative stress but not with inflammation: improvement by dietary supplementation with a melon superoxide dismutase.

    Science.gov (United States)

    Carillon, Julie; Romain, Cindy; Bardy, Guillaume; Fouret, Gilles; Feillet-Coudray, Christine; Gaillet, Sylvie; Lacan, Dominique; Cristol, Jean-Paul; Rouanet, Jean-Max

    2013-12-01

    Oxidative stress is involved in obesity. However, dietary antioxidants could prevent oxidative stress-induced damage. We have previously shown the preventive effects of a melon superoxide dismutase (SODB) on oxidative stress. However, the mechanism of action of SODB is still unknown. Here, we evaluated the effects of a 1-month curative supplementation with SODB on the liver of obese hamsters. Golden Syrian hamsters received either a standard diet or a cafeteria diet composed of high-fat, high-sugar, and high-salt supermarket products, for 15 weeks. This diet resulted in insulin resistance and in increased oxidative stress in the liver. However, inflammatory markers (IL-6, TNF-α, and NF-κB) were not enhanced and no liver steatosis was detected, although these are usually described in obesity-induced insulin resistance models. After the 1-month supplementation with SODB, body weight and insulin resistance induced by the cafeteria diet were reduced and hepatic oxidative stress was corrected. This could be due to the increased expression of the liver antioxidant defense proteins (manganese and copper/zinc superoxide dismutase, catalase, and glutathione peroxidase). Even though no inflammation was detected in the obese hamsters, inflammatory markers were decreased after SODB supplementation, probably through the reduction of oxidative stress. These findings suggest for the first time that SODB could exert its antioxidant properties by inducing the endogenous antioxidant defense. The mechanisms underlying this induction need to be further investigated. PMID:23792771

  2. Effects of Electroacupuncture on Pro-/Anti-inflammatory Adipokines in Serum and Adipose Tissue in Lean and Diet-induced Obese Rats.

    Science.gov (United States)

    Liaw, Jacqueline J T; Peplow, Philip V

    2016-04-01

    The effects of electroacupuncture (EA) on pro-/anti-inflammatory cytokines and blood glucose (BG) in lean and obese Long Evans rats were investigated. Group 1 and Group 3 had five lean and seven obese rats, respectively, and received EA at the Zhongwan/Guanyuan acupoints on Day 1, Day 3, Day 5, Day 8, Day 10, and Day 12. Group 2 and Group 4, with five lean and seven obese rats, respectively, did not undergo EA. After induction of anesthesia, BG was measured at 10 minutes and 20 minutes. EA was applied for 30 minutes, and BG was measured again. At the end of the study, blood and white adipose tissue were collected. Analyses showed that for all groups, the mean BG at 20 minutes (baseline) and 50 minutes were significantly greater on Day 1 than on any other day. Compared with Group 2, the baseline BG in Week 1 for Group 1 was significantly lower, but Groups 3 and 4 showed no difference. Group 1 had significantly higher serum interleukin-10 and tumor necrosis factor-α than Group 2, while Group 3's serum leptin was greater than Group 4's. White adipose tissue interleukin-10 and adiponectin:leptin ratio were higher for Group 1 than Group 2. EA affected no significant differences in any other components measured for lean and obese animals. PMID:27079227

  3. Green tea polyphenols benefits body composition and improves bone quality in long-term high-fat diet-induced obese rats

    Science.gov (United States)

    This study investigated the effects of green tea polyphenols (GTP) on body composition and 2 bone properties in obese female rats. Thirty-six 3-month-old SD female rats were fed either a 3 low-fat (LF) diet (n = 12) or a high-fat (HF) diet (n= 24) for 4 months. Animals in the LF diet 4 group continu...

  4. Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

    International Nuclear Information System (INIS)

    Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

  5. Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wei-Xin, E-mail: weixinliu@yahoo.com [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Wang, Ting; Zhou, Feng; Wang, Ying; Xing, Jun-Wei; Zhang, Shen [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Gu, Shou-Zhi [Department of Anatomy, Seirei Christopher College, Hamamatsu 433-8558 (Japan); Sang, Li-Xuan [Department of Cadre Ward II, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Dai, Cong [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Wang, Hai-Lan [Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, Guangdong (China)

    2015-04-10

    Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

  6. Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    Young-Sil; Lee; Bong-Keun; Choi; Hae; Jin; Lee; Dong-Ryung; Lee; Jinhua; Cheng; Won-Keun; Lee; Seung; Hwan; Yang; Joo-Won; Suh

    2015-01-01

    Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced obese mice,respectively.Methods:Black soybean was fermented with M.pilosus,and the main constituents in MFBS were analyzed by HPLC analysis.In vitro,MFBSE were examined for anti-adipogenic effects using Oil-Red O staining.In vivo,mice were fed a normal-fat diet(NFD)control,HFD control or HFD containing 1 g/kg MFBSP for 12 weeks,and then body weight gain and tissues weight measured.Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects.Results:MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity.MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice.MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes,such as peroxisome proliferator-activated receptorγ(PPARγ),fatty acid-binding protein 4(FABP4),and fatty acid synthase(FAS),in adipocytes and in white adipose tissue(WAT)of HFD-induced obese mice.Conclusions:These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFDinduced obese mice.

  7. COH-SR4 reduces body weight, improves glycemic control and prevents hepatic steatosis in high fat diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    James Lester Figarola

    Full Text Available Obesity is a chronic metabolic disorder caused by imbalance between energy intake and expenditure, and is one of the principal causative factors in the development of metabolic syndrome, diabetes and cancer. COH-SR4 ("SR4" is a novel investigational compound that has anti-cancer and anti-adipogenic properties. In this study, the effects of SR4 on metabolic alterations in high fat diet (HFD-induced obese C57BL/J6 mice were investigated. Oral feeding of SR4 (5 mg/kg body weight. in HFD mice for 6 weeks significantly reduced body weight, prevented hyperlipidemia and improved glycemic control without affecting food intake. These changes were associated with marked decreases in epididymal fat mass, adipocyte hypertrophy, increased plasma adiponectin and reduced leptin levels. SR4 treatment also decreased liver triglycerides, prevented hepatic steatosis, and normalized liver enzymes. Western blots demonstrated increased AMPK activation in liver and adipose tissues of SR4-treated HFD obese mice, while gene analyses by real time PCR showed COH-SR4 significantly suppressed the mRNA expression of lipogenic genes such as sterol regulatory element binding protein-1c (Srebf1, acetyl-Coenzyme A carboxylase (Acaca, peroxisome proliferator-activated receptor gamma (Pparg, fatty acid synthase (Fasn, stearoyl-Coenzyme A desaturase 1 (Scd1, carnitine palmitoyltransferase 1a (Cpt1a and 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr, as well as gluconeogenic genes phosphoenolpyruvate carboxykinase 1 (Pck1 and glucose-6-phosphatase (G6pc in the liver of obese mice. In vitro, SR4 activates AMPK independent of upstream kinases liver kinase B1 (LKB1 and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ. Together, these data suggest that SR4, a novel AMPK activator, may be a promising therapeutic compound for treatment of obesity, fatty liver disease, and related metabolic disorders.

  8. Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high-fat-diet-induced obese mice

    OpenAIRE

    Kawanishi, Noriaki; Niihara, Hiroyuki; Mizokami, Tsubasa; Yada, Koichi; Suzuki, Katsuhiko

    2015-01-01

    The innate immune system is associated with the development of local inflammation. Neutrophils play an essential role in the development of the adipose tissue (AT) inflammation associated with obesity by producing elastase, which can promote the activation and infiltration of macrophages. Exercise training attenuates AT inflammation via suppression of macrophage infiltration. However, the mechanisms driving this phenomenon remains to be elucidated. Here, we evaluated the effects of exercise t...

  9. Hypolipidemic effect of methanol fraction of Aconitum heterophyllum wall ex Royle and the mechanism of action in diet-induced obese rats

    OpenAIRE

    Arun Koorappally Subash; Anu Augustine

    2012-01-01

    Aconitum heterophyllum is an endangered Himalayan plant included in "lekhaneyagana," a pharmacological classification mentioned by Charaka in "Charakasamhita" which means reduce excess fat. The subterranean part of the plant is used for the treatment of diseases like nervous system disorders, fever, diarrhea, obesity, etc. In the present study, we are reporting the hypolipidemic effect of methanol fraction of A. heterophyllum. The methanol extract of A. heterophyllum was orally administered i...

  10. Hypolipidemic effect of methanol fraction of Aconitum heterophyllum wall ex Royle and the mechanism of action in diet-induced obese rats.

    OpenAIRE

    Arun Koorappally Subash; A Augustine

    2012-01-01

    Aconitum heterophyllum is an endangered Himalayan plant included in "lekhaneyagana," a pharmacological classification mentioned by Charaka in "Charakasamhita" which means reduce excess fat. The subterranean part of the plant is used for the treatment of diseases like nervous system disorders, fever, diarrhea, obesity, etc. In the present study, we are reporting the hypolipidemic effect of methanol fraction of A. heterophyllum. The methanol extract of A. heterophyllum was orally administered i...

  11. Possible modulation of FAS and PTP-1B signaling in ameliorative potential of Bombax ceiba against high fat diet induced obesity

    OpenAIRE

    Gupta, Paras; Goyal, Rohit; Chauhan, Yamini; Sharma, Pyare Lal

    2013-01-01

    Background Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains Lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. Methods Male Wistar albino ra...

  12. Loss of Protein Kinase Cβ Function Protects Mice Against Diet-Induced Obesity and Development of Hepatic Steatosis and Insulin Resistance

    OpenAIRE

    Huang, Wei; Bansode, Rishipal; Mehta, Madhu; Mehta, Kamal D

    2009-01-01

    Obesity is an energy balance disorder in which intake is greater than expenditure, with most excess calories stored as triglyceride (TG). We previously reported that mice lacking β-isoform of protein kinase C (PKCβ), a diacylglycerol- and phospholipid-dependent kinase, exhibit marked reduction in the whole body TG content, including white adipose tissue (WAT) mass. To investigate the role of this signaling kinase in metabolic adaptations to severe dietary stress, we studied the impact of a hi...

  13. Brown Fat and the Myth of Diet-Induced Thermogenesis

    OpenAIRE

    Kozak, Leslie P.

    2010-01-01

    The notion that brown adipose tissue (BAT) in mice or humans maintains energy balance by burning off excess calories seems incompatible with evolutionary biology. Studies in obese rats and mice lacking UCP1 indicate that diet-induced thermogenesis by BAT is unlikely.

  14. Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice

    Directory of Open Access Journals (Sweden)

    Yumiko Yoshizaki

    2014-08-01

    Full Text Available Rice koji is considered a readily accessible functional food that may have health-promoting effects. We investigated whether white, yellow, and red koji have the anti-obesity effect in C57BL/6J mice fed a high-fat diet (HFD, which is a model for obesity. Mice were fed HFD containing 10% (w/w of rice koji powder or steamed rice for 4 weeks. Weight gain, epididymal white adipose tissue, and total adipose tissue weight were significantly lower in all rice koji groups than in the HFD-rice group after 4 weeks. Feed efficiency was significantly reduced in the yellow koji group. Blood glucose levels were significantly lower in the white and red koji groups with HOMA-R and leptin levels being reduced in the white koji group. White and red koji increased glucose uptake and GLUT4 protein expression in L6 myotube cells. These results showed that all rice koji have the anti-obesity or anti-diabetes effects although the mechanisms may differ depending on the type of rice koji consumed.

  15. Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Maessen, Dionne E; Brouwers, Olaf; Gaens, Katrien H; Wouters, Kristiaan; Cleutjens, Jack P; Janssen, Ben J; Miyata, Toshio; Stehouwer, Coen D; Schalkwijk, Casper G

    2016-04-01

    Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity. PMID:26718500

  16. The Korean Mistletoe (Viscum album coloratum Extract Has an Antiobesity Effect and Protects against Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Hoe-Yune Jung

    2013-01-01

    Full Text Available This study investigates the inhibitory effects of Korean mistletoe extract (KME on adipogenic factors in 3T3-L1 cells and obesity and nonalcoholic fatty liver disease (NAFLD in mice fed a high-fat diet. Male C57Bl/6 mice fed a high-fat diet were treated with KME (3 g/kg/day for 15 weeks for the antiobesity and NAFLD experiments. Body weight and daily food intake were measured regularly during the experimental period. The epididymal pad was measured and liver histology was observed. The effects of KME on thermogenesis and endurance capacity were measured. The effects of KME on adipogenic factors were examined in 3T3-L1 cells. Body and epididymal fat pad weights were reduced in KME-treated mice, and histological examination showed an amelioration of fatty liver in KME-treated mice, without an effect on food consumption. KME potently induces mitochondrial activity by activating thermogenesis and improving endurance capacity. KME also inhibited adipogenic factors in vitro. These results demonstrate the inhibitory effects of KME on obesity and NAFLD in mice fed a high-fat diet. The effects appear to be mediated through an enhanced mitochondrial activity. Therefore, KME may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet.

  17. Radix Astragali Improves Dysregulated Triglyceride Metabolism and Attenuates Macrophage Infiltration in Adipose Tissue in High-Fat Diet-Induced Obese Male Rats through Activating mTORC1-PPARγ Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yang Long

    2014-01-01

    Full Text Available Increased levels of free fatty acids (FFAs and hypertriglyceridemia are important risk factors for cardiovascular disease. The effective fraction isolated from radix astragali (RA has been reported to alleviate hypertriglyceridemia. The mechanism of this triglyceride-lowering effect of RA is unclear. Here, we tested whether activation of the mTORC1-PPARγ signaling pathway is related to the triglyceride-lowering effect of RA. High-fat diet-induced obese (DIO rats were fed a high-fat diet (40% calories from fat for 9-10 weeks, and 4 g/kg/d RA was administered by gavage. RA treatment resulted in decreased fasting triglyceride levels, FFA concentrations, and adipocyte size. RA treated rats showed improved triglyceride clearance and fatty acid handling after olive oil overload. RA administration could also decrease macrophage infiltration and expression of MCP-1 and TNFα, but it may also increase the expression of PPARγ in epididymal adipose tissue from RA treated rats. Consistently, expressions of PPARγ and phospho-p70S6K were increased in differentiated 3T3-L1 adipocytes treated with RA. Moreover, RA couldnot upregulate the expression of PPARγ at the presence of rapamycin. In conclusion, the mTORC1-PPARγ signaling pathway is a potential mechanism through which RA exerts beneficial effects on the disturbance of triglyceride metabolism and dysfunction of adipose tissue in DIO rats.

  18. Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

    Science.gov (United States)

    Gotthardt, Juliet D; Verpeut, Jessica L; Yeomans, Bryn L; Yang, Jennifer A; Yasrebi, Ali; Roepke, Troy A; Bello, Nicholas T

    2016-02-01

    Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy. PMID:26653760

  19. Overexpression of β-Klotho in Adipose Tissue Sensitizes Male Mice to Endogenous FGF21 and Provides Protection From Diet-Induced Obesity.

    Science.gov (United States)

    Samms, Ricardo J; Cheng, Christine C; Kharitonenkov, Alexei; Gimeno, Ruth E; Adams, Andrew C

    2016-04-01

    The endocrine hormone fibroblast growth factor 21 (FGF21) is induced in the adaptive response to nutrient deprivation, where it serves to regulate the integrated response to fasting via its primary receptor complex, FGF receptor 1 coupled with the cofactor β-klotho (KLB) in target tissues. Curiously, endogenous FGF21 levels are also elevated in preclinical models of obesity and in obese/diabetic individuals. In addition to higher FGF21 levels, reduced KLB expression in liver and adipose tissue has been noted in these same individuals, suggesting that obesity may represent an FGF21 resistant state. To explore the contribution of tissue-specific KLB levels to endogenous FGF21 activity, in both fasting and high-fat diet feeding conditions, we generated animals overexpressing KLB in liver (LKLBOE) or adipose (ATKLBOE). Supportive of tissue-specific partitioning of FGF21 action, after chronic high-fat feeding, ATKLBOE mice gained significantly less weight than WT. Reduced weight gain was associated with elevated caloric expenditure, accompanied by a reduced respiratory exchange ratio and lower plasma free fatty acids levels, suggestive of augmented lipid metabolism. In contrast, LKLBOE had no effect on body weight but did reduce plasma cholesterol. The metabolic response to fasting was enhanced in LKLBOE mice, evidenced by increased ketone production, whereas no changes in this were noted in ATKLBOE mice. Taken together, these data provide further support that specific effects of FGF21 are mediated via engagement of distinct target organs. Furthermore, enhancing KLB expression in adipose may sensitize to endogenous FGF21, thus representing a novel strategy to combat metabolic disease. PMID:26901091

  20. Metabolic outcome of female mice exposed to a mixture of low-dose pollutants in a diet-induced obesity model.

    Science.gov (United States)

    Naville, Danielle; Labaronne, Emmanuel; Vega, Nathalie; Pinteur, Claudie; Canet-Soulas, Emmanuelle; Vidal, Hubert; Le Magueresse-Battistoni, Brigitte

    2015-01-01

    Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet. In the experimental studies described herein, we aimed to add further evidence on the metabolic impact of food pollutants using a recently set up model in which mice are life-long fed a high-fat/high-sucrose diet (HFSD) with/without common food pollutants shown to exhibit metabolic disrupting activities. Specifically, this mixture comprised bisphenol A, dioxin, polychlorobiphenyl PCB153, and phthalate and was added in HFSD at doses resulting in mice exposure at the Tolerable Daily Intake dose range for each pollutant. We herein focused on the 7-week-old females which exhibited early signs of obesity upon HFSD feeding. We observed no signs of toxicity and no additional weight gain following exposure to the mixture but alleviated HFSD-induced glucose intolerance in the absence of alteration of gluconeogenesis and steatosis. It suggested that the observed metabolic improvement was more likely due to effects on muscle and/or adipose tissues rather than on the liver. Consistently, female mice exhibited enhanced lean/fat mass ratio and skeletal muscle insulin sensitivity. Moreover, expression levels of inflammatory markers were reduced in adipose tissue at 7 but enhanced at 12 weeks of age in agreement with the inverse alterations of glucose tolerance observed at these ages upon pollutant exposure in the HFSD-fed females. Collectively, these data suggest apparent biphasic effects of pollutants upon HFSD feeding along with obesity development. These effects were not observed in males and may depend on interactions between diet and pollutants. PMID:25909471

  1. Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Rosa Martha Perez Gutierrez

    2014-01-01

    Full Text Available Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H in high-fat diet- (HFD- induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD and severely diabetic (SD mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

  2. Impact of Korean pine nut oil on weight gain and immune responses in high-fat diet-induced obese mice

    OpenAIRE

    Park, Soyoung; Lim, Yeseo; Shin, Sunhye; Han, Sung Nim

    2013-01-01

    Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or ...

  3. Indomethacin treatment prevents high fat diet-induced obesity and insulin resistance but not glucose intolerance in C57BL/6J Mice

    DEFF Research Database (Denmark)

    Fjære, Even; Aune, Ulrike Liisberg; Røen, Kristin;

    2014-01-01

    a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo...... by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response...

  4. Metabolic Outcome of Female Mice Exposed to a Mixture of Low-Dose Pollutants in a Diet-Induced Obesity Model

    OpenAIRE

    Vega, Nathalie; Pinteur, Claudie; Canet-Soulas, Emmanuelle; Vidal, Hubert

    2015-01-01

    Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet. In the experimental studies described herein, we aimed to add further evidence on the metabolic i...

  5. 5-HT2A/2C receptor and 5-HT transporter densities in mice prone or resistant to chronic high-fat diet-induced obesity: a quantitative autoradiography study.

    Science.gov (United States)

    Huang, Xu-Feng; Huang, Xin; Han, Mei; Chen, Feng; Storlien, Len; Lawrence, Andrew J

    2004-08-27

    The present study examined the density of 5-HT2A/2C receptors and 5-HT transporters in the brains of chronic high-fat diet-induced obese (cDIO) and obese-resistant (cDR) mice. Thirty-five male mice were used in this study. Twenty-eight mice were fed with a high-fat diet (40% of calories from fat) for 6 weeks and then classified as the cDIO (n=8) or cDR (n=8) mice according to the highest and lowest body weight gainers. Seven mice were placed on a low-fat diet (LF: 10% of calories from fat) and were used as controls. After 20 weeks of feeding, the sum of epididymal, perirenal, omental and inguinal fat masses was 9.3+/-0.3 g in the cDIO group versus 3.1+/-0.5 g in the cDR (pcDIO mice had a significantly higher 5-HT2A/2C binding density in the anterior olfactory nucleus and ventromedial hypothalamic nucleus (VMH) compared to the cDR and LF mice (+39% and +47%, p=0.003 and 0.045, respectively), whereas the latter two groups did not differ. The density of 5-HT2A/2C receptors in the VMH was associated with total amount of fat mass (r=0.617, p=0.032). On the other hand, the cDR mice had significantly lower 5-HT transporter binding than the cDIO and LF mice, respectively, in the nucleus accumbens (-44%, -38%, both pcDIO and cDR mice. It provides neural anatomical bases by which genetic variability in 5-HT2A/2C receptors and 5-HT transporter may influence satiety and sensory aspects of energy balance. PMID:15276882

  6. High-Fat Diet-Induced Neuropathy of Prediabetes and Obesity: Effect of PMI-5011, an Ethanolic Extract of Artemisia dracunculus L.

    Directory of Open Access Journals (Sweden)

    Pierre Watcho

    2010-01-01

    Full Text Available Artemisia species are a rich source of herbal remedies with antioxidant and anti-inflammatory properties. We evaluated PMI-5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-sfat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system. C57Bl6/J mice fed high-fat diet for 16 weeks developed obesity, moderate nonfasting hyperglycemia, nerve conduction deficit, thermal and mechanical hypoalgesia, and tactile allodynia. They displayed 12/15-lipoxygenase overexpression, 12(S-hydroxyeicosatetraenoic acid accumulation, and nitrosative stress in peripheral nerve and spinal cord. PMI-5011 (500 mgkg-1d-1, 7 weeks normalized glycemia, alleviated nerve conduction slowing and sensory neuropathy, and reduced 12/15-lipoxygenase upregulation and nitrated protein expression in peripheral nervous system. PMI-5011, a safe and nontoxic botanical extract, may find use in treatment of neuropathic changes at the earliest stage of disease.

  7. MGAT2 deficiency ameliorates high-fat diet-induced obesity and insulin resistance by inhibiting intestinal fat absorption in mice

    Directory of Open Access Journals (Sweden)

    Tsuchida Takuma

    2012-06-01

    Full Text Available Abstract Background Resynthesis of triglycerides in enterocytes of the small intestine plays a critical role in the absorption of dietary fat. Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2 is highly expressed in the small intestine and catalyzes the synthesis of diacylglycerol from monoacylglycerol and acyl-CoA. To determine the physiological importance of MGAT2 in metabolic disorders and lipid metabolism in the small intestine, we constructed and analyzed Mgat2-deficient mice. Results In oral fat tolerance test (OFTT, Mgat2-deficient mice absorbed less fat into the circulation. When maintained on a high-fat diet (HFD, Mgat2-deficient mice were protected from HFD-induced obesity and insulin resistance. Heterozygote (Mgat2+/− mice had an intermediate phenotype between Mgat2+/+ and Mgat2−/− and were partially protected from metabolic disorders. Despite of a decrease in fat absorption in the Mgat2-deficient mice, lipid levels in the feces and small intestine were comparable among the genotypes. Oxygen consumption was increased in the Mgat2-deficient mice when maintained on an HFD. A prominent upregulation of the genes involved in fatty acid oxidation was observed in the duodenum but not in the liver of the Mgat2-deficient mice. Conclusion These results suggest that MGAT2 has a pivotal role in lipid metabolism in the small intestine, and the inhibition of MGAT2 activity may be a promising strategy for the treatment of obesity-related metabolic disorders.

  8. Effect of hydroalcoholic fruit extract of Persea americana Mill. on high fat diet induced obesity: A dose response study in rats.

    Science.gov (United States)

    Monika, Padmanabhan; Geetha, Arumugam

    2016-06-01

    The fruits of Persea Americana Mill., commonly known as Avocado, are traditionally consumed for various health benefits including weight reduction. Here, we studied the effect of hydroalcoholic fruit extract of Persea americana (HAEPA) on high fat diet (HFD) induced obesity in rats. Obesity was induced in male Sprague Dawley rats by feeding HFD for 14 wk. The hypolipidemic effect was evaluated by co-administering 25, 50, 100 and 200 mg/kg body wt. of HAEPA. There was a significant increase in weight gain, body mass index (BMI), blood lipids, low density lipoproteins (LDL), lipid peroxides (LPO) and serum transaminases in HFD fed rats. HFD+HAEPA fed rats showed a significant decrease in blood lipids, LPO, liver lipids and increase in antioxidant status when compared to HFD control rats. The activity of lipid metabolic key enzymes such as fatty acid synthase and HMG CoA reductase in liver were also found to be decreased significantly in HAEPA co-administered rats. Lipoprotein lipase activity was found increased in HFD+HAEPA rats. Among the 4 doses studied, 100 mg of HAEPA/kg body wt. exhibited optimum hypolipidemic activity. Histopathological observations in liver and visceral adipose tissue added more evidence for the lipid lowering effect of HAEPA. It can be concluded that avocado fruit extract can act as hypolipidemic agent probably by modulating the activities of HMG CoA reductase and fatty acid synthase in liver. PMID:27468463

  9. Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice

    International Nuclear Information System (INIS)

    Metals and metalloid species are involved in homeostasis in energy systems such as glucose metabolism. Enlarged adipocytes are one of the most important causes of obesity-associated diseases. In this study, we studied the possibility that various metals, namely, CoCl2, HgCl2, NaAsO2 and MnCl2 pose risk to or have beneficial effects on white adipose tissue (WAT). Exposure to the four metals resulted in decreases in WAT weight and the size of enlarged adipocytes in mice fed a high-fat diet (HFD) without changes in liver weight, suggesting that the size and function of adipocytes are sensitive to metals. Repeated administration of CoCl2 significantly increased serum leptin, adiponectin and high-density lipoprotein (HDL) cholesterol levels and normalized glucose level and adipose cell size in mice fed HFD. In contrast, HgCl2 treatment significantly decreased serum leptin level with the down-regulation of leptin mRNA expression in WAT and a reduction in adipocyte size. Next, we tried to investigate possible factors that affect adipocyte size. Repeated exposure to HgCl2 significantly decreased the expression levels of factors upon the regulation of energy such as the PPARα and PPARγ mRNA expression levels in adipocytes, whereas CoCl2 had little effect on those genes expressions compared with that in the case of the mice fed HFD with a vehicle. In addition, repeated administration of CoCl2 enhanced AMPK activation in a dose-dependent manner in the liver, skeletal muscle and WAT; HgCl2 treatment also enhanced AMPK activation in the liver. Thus, both Co and Hg reduced WAT weight and the size of enlarged adipocytes, possibly mediated by AMKP activation in the mice fed HFD. However, inorganic cobalt may have a preventive role in obesity-related diseases through increased leptin, adiponectin and HDL-cholesterol levels, whereas inorganic mercury may accelerate the development of such diseases. These results may lead to the development of new approaches to establishing the

  10. Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u-ac.jp; Hanao, Norihide; Nishiyama, Kaori; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2012-01-01

    Metals and metalloid species are involved in homeostasis in energy systems such as glucose metabolism. Enlarged adipocytes are one of the most important causes of obesity-associated diseases. In this study, we studied the possibility that various metals, namely, CoCl{sub 2}, HgCl{sub 2}, NaAsO{sub 2} and MnCl{sub 2} pose risk to or have beneficial effects on white adipose tissue (WAT). Exposure to the four metals resulted in decreases in WAT weight and the size of enlarged adipocytes in mice fed a high-fat diet (HFD) without changes in liver weight, suggesting that the size and function of adipocytes are sensitive to metals. Repeated administration of CoCl{sub 2} significantly increased serum leptin, adiponectin and high-density lipoprotein (HDL) cholesterol levels and normalized glucose level and adipose cell size in mice fed HFD. In contrast, HgCl{sub 2} treatment significantly decreased serum leptin level with the down-regulation of leptin mRNA expression in WAT and a reduction in adipocyte size. Next, we tried to investigate possible factors that affect adipocyte size. Repeated exposure to HgCl{sub 2} significantly decreased the expression levels of factors upon the regulation of energy such as the PPARα and PPARγ mRNA expression levels in adipocytes, whereas CoCl{sub 2} had little effect on those genes expressions compared with that in the case of the mice fed HFD with a vehicle. In addition, repeated administration of CoCl{sub 2} enhanced AMPK activation in a dose-dependent manner in the liver, skeletal muscle and WAT; HgCl{sub 2} treatment also enhanced AMPK activation in the liver. Thus, both Co and Hg reduced WAT weight and the size of enlarged adipocytes, possibly mediated by AMKP activation in the mice fed HFD. However, inorganic cobalt may have a preventive role in obesity-related diseases through increased leptin, adiponectin and HDL-cholesterol levels, whereas inorganic mercury may accelerate the development of such diseases. These results may lead

  11. Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Koppo, Katrien; Siklová-Vitková, Michaela; Klimcáková, Eva;

    2012-01-01

    The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo...... low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at...... baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during...

  12. Antihyperglycemic and Anti-Inflammatory Effects of Standardized Curcuma xanthorrhiza Roxb. Extract and Its Active Compound Xanthorrhizol in High-Fat Diet-Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Mi-Bo Kim

    2014-01-01

    Full Text Available Xanthorrhizol, a natural compound isolated from Curcuma xanthorrhiza Roxb. (Java turmeric, has been reported to possess antioxidant and anticancer properties; however, its effects on metabolic disorders remain unknown. The aim of the present study was to evaluate the effects of xanthorrhizol (XAN and C. xanthorrhiza extract (CXE with standardized XAN on hyperglycemia and inflammatory markers in high-fat diet- (HFD- induced obese mice. Treatment with XAN (10 or 25 mg/kg/day or CXE (50 or 100 mg/kg/day significantly decreased fasting and postprandial blood glucose levels in HFD-induced obese mice. XAN and CXE treatments also lowered insulin, glucose, free fatty acid (FFA, and triglyceride (TG levels in serum. Epididymal fat pad and adipocyte size were decreased by high doses of XAN (26.6% and 20.1% and CXE (25.8% and 22.5%, respectively. XAN and CXE treatment also suppressed the development of fatty liver by decreasing liver fat accumulation. Moreover, XAN and CXE significantly inhibited production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, interleukin-1β (IL-1β, and C-reactive protein (CRP in adipose tissue (27.8–82.7%, liver (43.9–84.7%, and muscle (65.2–92.5%. Overall, these results suggest that XAN and CXE, with their antihyperglycemic and anti-inflammatory activities, might be used as potent antidiabetic agents for the treatment of type 2 diabetes.

  13. The lysyl oxidase inhibitor (β-aminopropionitrile) reduces leptin profibrotic effects and ameliorates cardiovascular remodeling in diet-induced obesity in rats.

    Science.gov (United States)

    Martínez-Martínez, Ernesto; Rodríguez, Cristina; Galán, María; Miana, María; Jurado-López, Raquel; Bartolomé, María Visitación; Luaces, María; Islas, Fabián; Martínez-González, José; López-Andrés, Natalia; Cachofeiro, Victoria

    2016-03-01

    Lysyl oxidase (LOX) is an extracellular matrix (ECM)-modifying enzyme that has been involved in cardiovascular remodeling. We explore the impact of LOX inhibition in ECM alterations induced by obesity in the cardiovascular system. LOX is overexpressed in the heart and aorta from rats fed a high-fat diet (HFD). β-Aminopropionitrile (BAPN), an inhibitor of LOX activity, significantly attenuated the increase in body weight and cardiac hypertrophy observed in HFD rats. No significant differences were found in cardiac function or blood pressure among any group. However, HFD rats showed cardiac and vascular fibrosis and enhanced levels of superoxide anion (O2(-)), collagen I and transforming growth factor β (TGF-β) in heart and aorta and connective tissue growth factor (CTGF) in aorta, effects that were attenuated by LOX inhibition. Interestingly, BAPN also prevented the increase in circulating leptin levels detected in HFD fed animals. Leptin increased protein levels of collagen I, TGF-β and CTGF, Akt phosphorylation and O2(-) production in both cardiac myofibroblasts and vascular smooth muscle cells in culture, while LOX inhibition ameliorated these alterations. LOX knockdown also attenuated leptin-induced collagen I production in cardiovascular cells. Our findings indicate that LOX inhibition attenuates the fibrosis and the oxidative stress induced by a HFD on the cardiovascular system. The reduction of leptin levels by BAPN in vivo and the ability of this compound to inhibit leptin-induced profibrotic mediators and ROS production in cardiac and vascular cells suggest that interactions between leptin and LOX regulate downstream events responsible for myocardial and vascular fibrosis in obesity. PMID:26780438

  14. Euterpe oleracea Mart.-Derived Polyphenols Protect Mice from Diet-Induced Obesity and Fatty Liver by Regulating Hepatic Lipogenesis and Cholesterol Excretion.

    Directory of Open Access Journals (Sweden)

    Paola Raquel B de Oliveira

    Full Text Available The aim of this study was to investigate the effect of a polyphenol-rich Açaí seed extract (ASE, 300 mg/kg-1d-1 on adiposity and hepatic steatosis in mice that were fed a high-fat (HF diet and its underlying mechanisms based on hepatic lipid metabolism and oxidative stress. Four groups were studied: C57BL/6 mice that were fed with standard diet (10% fat, Control, 10% fat + ASE (ASE, 60% fat (HF, and 60% fat + ASE (HF + ASE for 12 weeks. We evaluated the food intake, body weight gain, serum glucose and lipid profile, hepatic cholesterol and triacyglycerol (TG, hepatic expression of pAMPK, lipogenic proteins (SREBP-1c, pACC, ACC, HMG-CoA reductase and cholesterol excretion transporters, ABCG5 and ABCG8. We also evaluated the steatosis in liver sections and oxidative stress. ASE reduced body weight gain, food intake, glucose levels, accumulation of cholesterol and TG in the liver, which was associated with a reduction of hepatic steatosis. The increased expressions of SREBP-1c and HMG-CoA reductase and reduced expressions of pAMPK and pACC/ACC in HF group were antagonized by ASE. The ABCG5 and ABCG8 transporters expressions were increased by the extract. The antioxidant effect of ASE was demonstrated in liver of HF mice by restoration of SOD, CAT and GPx activities and reduction of the increased levels of malondialdehyde and protein carbonylation. In conclusion, ASE substantially reduced the obesity and hepatic steatosis induced by HF diet by reducing lipogenesis, increasing cholesterol excretion and improving oxidative stress in the liver, providing a nutritional resource for prevention of obesity-related adiposity and hepatic steatosis.

  15. Calorie control increased vaspin levels of serum and periepididymal adipose tissue in diet-induced obese rats in association with serum free fatty acid and tumor necrosis factor alpha

    Institute of Scientific and Technical Information of China (English)

    WANG You-min; WANG Wen-ping; WANG Li-ping; L(U) Qi-huan; ZHOU Xiao-hui

    2010-01-01

    Background Vaspin was recently identified as a novel adipokine that is predominantly secreted from adipose tissue and exerts insulin-sensitizing effects. This study was undertaken to elucidate the regulative effects of calorie control on the expression of vaspin and its potential mechanism.Methods Diet-induced obese Sprague Dawley (SD) rats were adopted as experimental models and accepted interventions of various ingestions and pioglitazone. Various differentiated stages of cultured 3T3-L1 cells were dealt with pioglitazone or TNFα in vitro for 48 hours to further verify findings in animal experiments.Results The rats were successfully induced into an obese experimental model with hyperinsulinemia, hyperlipidemia, and increased serum free fatty acid and TNFa by 12-week high-fat diet. It was found that depending on whether the rats were fed by a high-fat diet or a basal diet, there was extremely higher vaspin in the periepididymal fat pad than in subcutaneous adipose tissues by 16 weeks. Vaspin in sera and the periepididymal fat pad was much lower in rats with a high-fat diet than those with a basal diet (all P <0.05), but vaspin in subcutaneous fat tissues was prone to increase in rats with a high-fat diet. A 4-week calorie restriction or pioglitazone on the obese rats resulted in a partial recovery of vaspin levels in sera and periepididymal adipose tissues, especially the latter revealed a more obvious superiority and increased vaspin levels of subcutaneous adipose. Surprisingly, the treatment of 4-week high-fat diet on non-obese rats did not significantly depress vaspin of sera and periepididymal adipose tissues. However, it is unknown if re-feeding generated the effect on vaspin levels of obese and non-obese rats on sera or adipose tissues. The correlation analysis showed that vaspin levels of serum and periepididymal fat tissues were negatively correlated with serum FFA, TNFα and insulin; meanwhile, there was a positive correlation between serum vaspin and

  16. Vinegar-Baked Radix Bupleuri Regulates Lipid Disorders via a Pathway Dependent on Peroxisome-Proliferator-Activated Receptor-α in High-Fat-Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Thing-Fong Tzeng

    2012-01-01

    Full Text Available The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of vinegar-baked Radix Bupleuri (VBRB on high-fat diet- (HFD- induced obese rats. After being fed HFD for two weeks, rats were dosed orally with VBRB or fenofibrate, once daily for further twelve weeks. VBRB (1.0 g kg−1 per day produced effects similar to fenofibrate (100 mg kg−1 in reducing body weight (BW gain, visceral fat-pad weights, plasma lipid levels, as well as hepatic TG and cholesterol content of HFD-fed rats. VBRB also lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. VBRB and fenofibrate reversed the HFD-induced downregulation of hepatic peroxisome proliferator-activated receptor (PPARα. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO and cytochrome P450 isoform 4A1 (CYP4A1 proteins were reversed by VBRB and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs in HFD-fed rats was lowered by VBRB and fenofibrate. The results of this study show that VBRB suppresses BW gain and body fat accumulation by increasing fatty acid oxidation, an effect which is likely mediated via upregulation of PPARα and downregulation of SREBP expression in the liver of HFD-fed rats.

  17. High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon.

    Science.gov (United States)

    Bhattarai, Yogesh; Fried, David; Gulbransen, Brian; Kadrofske, Mark; Fernandes, Roxanne; Xu, Hui; Galligan, James

    2016-08-01

    We tested the hypothesis that colonic enteric neurotransmission and smooth muscle cell (SMC) function are altered in mice fed a high-fat diet (HFD). We used wild-type (WT) mice and mice lacking the β1-subunit of the BK channel (BKβ1 (-/-)). WT mice fed a HFD had increased myenteric plexus oxidative stress, a 28% decrease in nitrergic neurons, and a 20% decrease in basal nitric oxide (NO) levels. Circular muscle inhibitory junction potentials (IJPs) were reduced in HFD WT mice. The NO synthase inhibitor nitro-l-arginine (NLA) was less effective at inhibiting relaxations in HFD compared with control diet (CD) WT mice (11 vs. 37%, P < 0.05). SMCs from HFD WT mice had depolarized membrane potentials (-47 ± 2 mV) and continuous action potential firing compared with CD WT mice (-53 ± 2 mV, P < 0.05), which showed rhythmic firing. SMCs from HFD or CD fed BKβ1 (-/-) mice fired action potentials continuously. NLA depolarized membrane potential and caused continuous firing only in SMCs from CD WT mice. Sodium nitroprusside (NO donor) hyperpolarized membrane potential and changed continuous to rhythmic action potential firing in SMCs from HFD WT and BKβ1 (-/-) mice. Migrating motor complexes were disrupted in colons from BKβ1 (-/-) mice and HFD WT mice. BK channel α-subunit protein and β1-subunit mRNA expression were similar in CD and HFD WT mice. We conclude that HFD-induced obesity disrupts inhibitory neuromuscular transmission, SMC excitability, and colonic motility by promoting oxidative stress, loss of nitrergic neurons, and SMC BK channel dysfunction. PMID:27288421

  18. Peroxisome proliferator-activated receptors (PPARs-independent functions of fish oil on glucose and lipid metabolism in diet-induced obese mice

    Directory of Open Access Journals (Sweden)

    Wakutsu Masaki

    2010-09-01

    Full Text Available Abstract Background Fish oil is known to improve lifestyle-related diseases. These effects occur partly via activation of PPARs by the n-3 polyunsaturated fatty acids included abundantly in fish oil. We investigated fish oil functions on glucose and lipid metabolism that are both dependent on and independent of PPARs pathway. Methods Mice were fed a diet containing 30 en% beef tallow (B diet for twelve weeks to induce obesity. The mice were then divided into two groups which were fed either a B diet or a diet containing 30 en% fish oil (F diet. Each group was further divided into two groups which were administered PPARα and γ antagonists or vehicle once a day for three weeks. Results The F diet groups showed lower triglyceride levels in plasma and liver than the B diet groups, but PPARs antagonists did not affect the triglyceride levels in either diet groups. The F diet groups also showed improvement of glucose tolerance compared with the B diet groups. However, PPARs antagonists made glucose tolerance worse in the F diet group but improved it in the B diet group. Therefore, by the administration of antagonists, glucose tolerance was inversely regulated between the B and F diets, and hypolipidemic action in the plasma and liver of the F diet group was not affected. Conclusion These results suggest that fish oil decreases lipid levels in plasma and liver via PPARs pathway-independent mechanism, and that glucose tolerance is inversely regulated by PPARs antagonists under diets containing different oils.

  19. Diet-induced obesity resistance of adult female mice selectively bred for increased wheel-running behavior is reversed by single perinatal exposure to a high-energy diet.

    Science.gov (United States)

    Guidotti, Stefano; Meyer, Neele; Przybyt, Ewa; Scheurink, Anton J W; Harmsen, Martin C; Garland, Theodore; van Dijk, Gertjan

    2016-04-01

    Female mice from independently bred lines previously selected over 50 generations for increased voluntary wheel-running behavior (S1, S2) resist high energy (HE) diet-induced obesity (DIO) at adulthood, even without actual access to running wheels, as opposed to randomly bred controls (CON). We investigated whether adult S mice without wheels remain DIO-resistant when exposed - via the mother - to the HE diet during their perinatal stage (from 2 weeks prior to conception until weaning on post-natal day 21). While S1 and S2 females subjected to HE diet either perinatally or from weaning onwards (post-weaning) resisted increased adiposity at adulthood (as opposed to CON females), they lost this resistance when challenged with HE diet during these periods combined over one single cycle of breeding. When allowed one-week access to wheels (at week 6-8 and at 10 months), however, tendency for increased wheel-running behavior of S mice was unaltered. Thus, the trait for increased wheel-running behavior remained intact following combined perinatal and post-weaning HE exposure, but apparently this did not block HE-induced weight gain. At weaning, perinatal HE diet increased adiposity in all lines, but this was only associated with hyperleptinemia in S lines irrespective of gender. Because leptin has multiple developmental effects at adolescence, we argue that a trait for increased physical activity may advance maturation in times of plenty. This would be adaptive in nature where episodes of increased nutrient availability should be exploited maximally. Associated disturbances in glucose homeostasis and related co-morbidities at adulthood are probably pleiotropic side effects. PMID:26850290

  20. Resveratrol ameliorates the lipid metabolism in the diet-induced obese zebraifsh%白藜芦醇改善饮食诱导肥胖斑马鱼脂代谢的研究

    Institute of Scientific and Technical Information of China (English)

    冉盖; 应力; 李琳; 邓拓; 燕乔乔; 应晨江; 叶晓蕾

    2016-01-01

    目的:研究白藜芦醇(RSV)对饮食诱导肥胖斑马鱼脂代谢的影响。方法:120条野生型成年雄性斑马鱼(AB系),随机分为4组,即正常喂饲组(Con),正常喂饲+RSV组(Con+RSV),过度喂饲组(DIO),过度喂饲+RSV组(DIO+RSV)。每条鱼正常喂饲虫卵量每天为8 mg,过量喂饲量为每天60 mg,RSV干预剂量为20μmol/L,每天11 h。实验持续8周。实验结束时测定鱼体长、体质量,计算肥满度,检测血浆甘油三酯(TG)和总胆固醇(TC),观察肝组织形态。检测鱼体pAMPKα/AMPKα、Sirt1、Cav-1和LC3蛋白表达水平。结果:DIO组斑马鱼体长、体质量和肥满度较对照组分别增加11.7%、61.9%和15.1%(P<0.01),虽然喂食量和RSV对斑马鱼体长的影响存在交互效应(P<0.05),但RSV干预对上述指标的影响差异均无统计学意义(P>0.05)。RSV干预能显著改善过度喂饲诱导的脂肪浸润和肝脏脂滴形成,上调鱼体AMPKα蛋白磷酸化水平及显著提升Sirt1蛋白表达水平(725.8% DIO+RSV组 vs DIO组,P<0.01),RSV干预同时显著提升自噬标志蛋白LC3-II的水平(P<0.05)。结论:RSV在没有影响体长、体质量和血脂的情况下,可以调节饮食诱导肥胖斑马鱼的脂代谢,这可能与pAMPKa/Sirt1/自噬通路有关。%Objective:To investigate the effect of resveratrol (RSV) on lipid metabolism in diet-induced obese zebrafish. Methods: One hundred and twenty adult zebrafish (Danio rerio) of the wild-type strain (AB) were randomly allocated into 4 groups: control group (Con), Con+RSV, diet-induced obese (DIO), and DIO+RSV. The Con group was fed on freshly hatched live Artemia (8 mg cysts/ifsh/day) once a day for 8 weeks. The DIO group was fed on freshly hatched live Artemia (60 mg cysts/ifsh/day) three times a day for 8 weeks. The ifsh were exposed to 20 mmol/L resveratrol for 11 hours every day. After 8 weeks, the body length

  1. 游泳运动对高脂诱导肥胖SD大鼠Ghrelin表达的影响%Effects of swimming exercise on Ghrelin levels in high-diet induced obesity SD rats

    Institute of Scientific and Technical Information of China (English)

    高雅; 潘天荣; 王长江

    2013-01-01

    目的:观察游泳运动干预后肥胖大鼠血清及下丘脑Ghrelin水平的变化,探讨其在肥胖及代谢紊乱中的作用.方法:SD大鼠50只随机分为普食(NC,n=10)组和高脂(HD,n=40)组.筛选出成功建立肥胖模型20只随机分为肥胖对照(OB)组、游泳(SWI)组,各10只.SWI组予以每天1 h,每周5 d,共行6周游泳训练;OB组及NC组予等剂量蒸馏水灌胃.分别测定干预6周前后各组体重(BW)、空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TCH)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)及血清Ghrelin.免疫组织化学法检测各组大鼠下丘脑Ghrelin表达水平.结果:干预前,OB组、SWI组均较NC组BW、FPG、TG、TCH、FINS、HOMA-IR显著升高,Ghrelin明显降低(P<0.01);干预后,SWI组均较OB组BW、TG、TCH、FPG、FINS、HOMA-IR明显降低,Ghrelin水平升高(P<0.01).免疫组织化学显示OB组下丘脑Ghrelin表达较NC组降低(P<0.01),SWI组较OB组升高(P<0.05).结论:游泳运动可改善胰岛素敏感性并减轻体重,降低肥胖大鼠Ghrelin水平.%Objective: To observe the changes of Ghrelin level in serum and hypothalamus of high-diet induced obesity rats after 6-week swimming exercise,and to investigate the association of Ghrelin with obesity and metabolic syndrome. Methods:Fifty SD rats were randomly divided into normal diet group( NC,n = 10) and high fat diet group(HD,n =40). Obesity models(n =20) were established from the HD group, and equally assigned to obesity group ( OB) and swimming exercise group ( SWI) . The SWI group received standard swimming exercise 1 hour/day,5 day/week for 6 weeks,and the other two groups were given distilled water. Their body weight( BW) , fasting plasma glucose(FPG) ,triglyceride(TG) ,total cholesterol(TCH) ,fasting insulin(FINS) ,H0MA index and fasting Ghrelin were measured 6 weeks before and after the intervene; the Ghrelin expression in the hypothalamus was detected by immunohistochemistry. Results:The BW

  2. Effects of BVT.2733 on the expression of Visfatin in mice with diet-induced obesity%BVT.2733影响饮食诱导肥胖小鼠中Visfatin表达的研究

    Institute of Scientific and Technical Information of China (English)

    谢宇; 姜敏; 尹震宇; 丁国宪; 王春

    2012-01-01

    目的:构建高脂饮食诱导肥胖小鼠模型,观察BVT.2733在改善胰岛素抵抗中的作用及对Visfatin表达的影响.方法:构建高脂饮食诱导的肥胖小鼠模型,分为肥胖对照组和BVT.2733治疗组,肥胖对照组给予安慰剂、治疗组给予BVT.2733灌胃2周,同时设正常饮食的小鼠为正常对照组.放射免疫法测小鼠空腹胰岛素水平,生化法检测血糖,实时定量RT-PCR检测内脏脂肪组织Visfatin的mRNA表达.观察各组小鼠脂肪组织的形态学变化.结果:与正常对照组相比,肥胖对照组小鼠脂肪细胞明显增大,体重增加,空腹血糖、血清胰岛素水平升高(P<0.05).与肥胖对照组相比,BVT.2733治疗组小鼠脂肪细胞体积减小,空腹血清胰岛素水平明显下降(P<0.01),脂肪组织Visfatin mRNA表达显著降低(p<0.05).结论:BVT.2733能够降低体重,减少脂肪组织,并且降低Visfatin的表达水平.%Objective:To investigate the effects of BVT.2733 on the expression of Visfatin and insulin resistance in the diet-induced obese (DIO) mice model. Methods:The C57BL/6J mice were randomly divided into the normal diet group and high-fat diet (HFD) group. After 20 weeks,the obese mice were randomly divided into obese control group and BVT.2733 treatment group. And they were orally administered placebo and BVT.2733, respectively, for two weeks. The levels of plasma glucose and serum insulin were measured by biochemistry technology and radioimmumty. The visfatin mRNA expression in adipose tissue were analyzed by realtime quantitative PCR. And the morphology changes of adipocyte were also observed. Results:Comparing to normal controls,the weight,plasma glucose and serum insulin levels increased in HFD group (P < 0.05) ,and the size of adipocyte in HFD group was big. Comparing to obese controls,in BVT.2733 treatment group,the serum insulin significantly decreased (P < 0.01) and the adipocyte sizes reduced,while the mRNA expression of Visfatin down

  3. Vascular rarefaction mediates whitening of brown fat in obesity

    OpenAIRE

    Shimizu, Ippei; Aprahamian, Tamar; Kikuchi, Ryosuke; Shimizu, Ayako; Papanicolaou, Kyriakos N.; MacLauchlan, Susan; Maruyama, Sonomi; Walsh, Kenneth

    2014-01-01

    Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet ...

  4. Diet-Induced and Age-Related Changes in the Quadriceps Muscle: MRI and MRS in a Rat Model of Sarcopenia

    OpenAIRE

    Fellner, Claudia; Schick, Fritz; Kob, Robert; Hechtl, Christine; Vorbuchner, Marianne; Büttner, Roland; Hamer, Okka W.; Sieber, Cornel C.; Stroszczynski, Christian; Bollheimer, L Cornelius

    2014-01-01

    Background: Knowledge about the molecular pathomechanisms of sarcopenia is still sparse, especially with regard to nutritional risk factors and the subtype of sarcopenic obesity. Objective: The aim of this study was to characterize diet-induced and age-related changes on the quality and quantity of the quadriceps muscle in a rat model of sarcopenia by different magnetic resonance (MR) techniques. Methods: A total of 36 6-month-old male Sprague-Dawley rats were randomly subdivid...

  5. Effect of Shengqing Herbs on Leptin Resistance of Diet-Induced Obesity Rats%升清中药对饮食诱导肥胖大鼠瘦素抵抗的影响

    Institute of Scientific and Technical Information of China (English)

    姜萍; 宋钦兰

    2014-01-01

    目的:探讨升清中药抑制饮食诱导肥胖(DIO)大鼠肥胖及瘦素抵抗的作用机制。方法取 Wistar大鼠,制作DIO大鼠40只和DIO抵抗(DIO-R)大鼠10只。DIO大鼠分为模型组、西布曲明组、健脾理气组、升清组,每日分别以生理盐水、西布曲明、健脾理气药物(陈皮、木香、枳实)、升清药物(柴胡、升麻、葛根)灌胃,空白组与DIO-R组予生理盐水,灌胃16周。测定干预前后体质量,检测干预后血清神经肽Y(NPY)、瘦素和脂肪瘦素、细胞因子信号传导抑制因子3(SOCS-3)。结果与DIO-R组比较,模型组体质量增加、NPY升高(P<0.01),血清和脂肪瘦素降低(P<0.05),SOCS-3升高(P<0.05)。药物干预后,各药物组体质量有所下降。健脾理气组脂肪瘦素升高(P<0.05);升清组在升高瘦素、降低体质量和 NPY、SOCS-3水平方面,优于西布曲明组和健脾理气组,差异有统计学意义(P<0.05,P<0.01)。结论升清药物能减轻肥胖,抑制瘦素抵抗。%Objective To observe the effects of Shengqing Chinese herbs on the obesity and leptin resistance of diet-induced obesity (DIO) rats.Methods Wistar rats were produced a rat model including of 40 DIO rats and 10 DIO-R rats. The DIO rats were divided into DIO model group, sibutramine group, Jianpi Liqi group and Shengqing group, which were respectively by gavage of saline, sibutramine, Jianpi Liqi herbs (Citri reticulatae pericarpium, Aucklandiae radix, Aurantii fructus immaturus), Shengqing herbs (Bupleuri radix, Cimicifugae rhizoma, Puerariae lobatae radix), blank control group and DIO-R group were by gavage of saline. Their weight, were examined after 16 weeks gavage. Leptin and neuropeptide Y in the serum were examined. Leptin, TNF-α, and suppressors of cytokine signaling-3 (SOCS-3) in the homogenized fat were examined. Results Compared with the DIO-R group, DIO model group's body weight, NPY significantly increased (P<0.01);leptin in the serum and homogenized

  6. Voluntary Exercise Improves High-Fat Diet-Induced Leptin Resistance Independent of Adiposity

    OpenAIRE

    Carhuatanta, Kimberly A. Krawczewski; Demuro, Giovanna; Tschöp, Matthias H.; Pfluger, Paul T.; Benoit, Stephen C.; Obici, Silvana

    2011-01-01

    The efficacy of exercise as primary prevention of obesity is the subject of intense investigation. Here, we show that voluntary exercise in a mouse strain susceptible to diet-induced obesity (C57B6J) decreases fat mass and increases energy expenditure. In addition, exercise attenuates obesity in mice fed a high-fat diet (HFD). Using FosB immunoreactivity as a marker of chronic neuronal activation, we found that exercise activates leptin receptor-positive neurons in the ventromedial hypothalam...

  7. Molecular signatures for obesity and associated disorders identified through partial least square regression models

    OpenAIRE

    Sinha, Neeraj; Sharma, Sachin; Tripathi, Parul; Negi, Simarjeet Kaur; Tikoo, Kamiya; Kumar, Dhiraj; Rao, Kanury VS; Chatterjee, Samrat

    2014-01-01

    Background Obesity is now a worldwide epidemic disease and poses a major risk for diet related diseases like type 2 diabetes, cardiovascular disease, stroke and fatty liver among others. In the present study we employed the murine model of diet-induced obesity to determine the early, tissue-specific, gene expression signatures that characterized progression to obesity and type 2 diabetes. Results We used the C57BL/6 J mouse which is known as a counterpart for diet-induced human diabetes and o...

  8. Immunity-Based Evolutionary Interpretation of Diet-Induced Thermogenesis.

    Science.gov (United States)

    Liao, Wan-Hui; Henneberg, Maciej; Langhans, Wolfgang

    2016-06-14

    Diet-induced thermogenesis (DIT) has often been argued to be a physiological defense against obesity, but no empirical proof of its effectiveness in limiting human body weight gain is available. We here propose an immune explanation of DIT-i.e., that it results from the coevolution of host and gut microbiota (especially Firmicutes) that ferment ingested food and proliferate, causing periodic, vagally mediated increases in thermogenesis aimed at curtailing their expansion. Because of this evolutionary adaptive significance related to the immune system, DIT is not effective as an "adaptation" to maintain a certain body mass. Were DIT an effective adaptation to prevent obesity, the current obesity epidemic might not have occurred. PMID:27304499

  9. Göttingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals

    DEFF Research Database (Denmark)

    Ludvigsen, Trine Pagh; Kirk, Rikke Kaae; Christoffersen, Berit Østergaard;

    2015-01-01

    From a pharmacological perspective, readily-available, well-characterized animal models of cardiovascular disease, including relevant in vivo markers of atherosclerosis are important for evaluation of novel drug candidates. Furthermore, considering the impact of diabetes mellitus on atherosclerosis...... metabolism were evaluated together with coronary and aortic atherosclerosis after 22 or 43 diet-weeks. Group differences were evaluated by analysis of variance for parametric data and Kruskal-Wallis test for non-parametric data. For qualitative assessments, Fisher's exact test was applied. For all analyses...

  10. Mechanism of retinal ganglion cells apoptosis in the diet -induced obese C57 BL/6 mice%膳食诱导的肥胖型 C57 BL/6小鼠视网膜神经节细胞凋亡的机制

    Institute of Scientific and Technical Information of China (English)

    白霞; 赵剑; 赵文青; 陈玉玲

    2014-01-01

    AIM:To investigate the mechanism of retinal ganglion cells (RGCs) apoptosis in the diet-induced obese C57BL/6 mice. METHODS: Mice were fed high-fat diet. After 19 weeks of feeding, the mice were divided into diet induced obesity-resistant ( DIO-R ) group and diet induced obesity ( DIO) group, while mice of the control ( CON) group were fed a basal diet at the same time. The apoptosis of RGCs was detected by TUNEL.Laser scanning confocal microscope was used to detect the intracellular calcium ion concentration. RESULTS: TUNEL staining showed apoptosis cells in ganglion cell layer ( GCL) in DIO group increased and the percentage of apoptotic cells was (6.7±1.2)%which was much higher than in CON and DIO-R groups ( P0.05 ).Laser scanning confocal microscope detection showed Ca2+ staining intensity of RGCs in DIO group increased and its staining intensity was significantly higher than in CON and DIO-R mice (P0.05 ) . CONCLUSION:Intracellular calcium ion overload might be involved in the RGCs apoptosis in the diet-induced obese C57BL/6 mice.%目的:探讨高脂饮食诱导的C57 BL/6肥胖小鼠视网膜神经节细胞( RGCs)凋亡的机制。  方法:高脂饲料喂养19 wk后,小鼠分为肥胖抵抗( DIO-R)组和肥胖倾向( DIO)组,同时对照组( CON)小鼠给予基础饲料。 TUNEL法检测各组小鼠RGCs的凋亡情况,并应用激光共聚焦显微镜检测RGCs内钙离子的浓度。  结果:TUNEL法凋亡检测结果显示,DIO组小鼠视网膜神经节细胞层可见较多黄色着染的凋亡细胞,其凋亡指数为(6.7±1.2)%,显著高于对照组和DIO-R组(P<0.01, P<0.05);对照组和DIO-R组间比较无显著差异( P>0.05)。激光共聚焦结果显示,与对照组和DIO-R组比较,DIO组小鼠视网膜神经节细胞内Ca2+荧光染色明显增强,其荧光染色强度比值显著升高(均P<0.01);对照组和DIO-R组视网膜神经节细胞内Ca2+荧

  11. Effects of Resistant Starch on Defecation and Intestinal Microflora of Diet Induced Obesity Rats%抗性淀粉对饮食诱导肥胖大鼠排便状况及肠道菌群的影响

    Institute of Scientific and Technical Information of China (English)

    王志凡; 杨秀琳; 陈旺盛; 马慧

    2016-01-01

    的肠道菌群紊乱。%This experiment was conducted to discuss the influence of resistant starch ( RS) on defecation and intestinal microflora of diet induced obesity ( DIO) rat, to provide basis for the usage of RS. A total of 100 health male SD rats were randomly divided into two groups, basal diet was given to the control group which with ten rats and the high⁃fat diet was given to the high⁃fat group ( HF group) which with ninety rats for seven weeks. Then twenty⁃seven DIO rats were picked out on the ground of their weight from the HF group, and ran⁃domly divided into three groups with nine replicates per group. Each group was offered one of the following di⁃ets:the high⁃fat diet in HF group, the high⁃fat diet with 10% RS in high⁃fat and resistant starch group ( HFRS group) and high⁃fat and resistant starch+dextran sulfate group ( HFRS+DS group) . The experimental period was five weeks. During period, 1 mL 5% DS was given by gavage to HFRS+DS group, while 1 mL distilled water was administrated to other two groups. One gram fresh feces was collected in the 7th and the 12th week. The number of Bacillus coli, Enterococcus, Bacillus bifidus, Lacticacid bacillus, and Bacteroid were tested u⁃sing selective culture medium after dilution. The results showed as follows:1) in the 7th week, compared with the control group, wet weight and water content of feces, and the number of Enterococcus, Bacillus bifidus, Lacticacid bacillus and Bacteroid of feces in HF group were significantly decreased ( P<0.05) , while the pellet number and the Bacillus coli number of feces in HF group were significantly increased (P<0.05). 2) In the 12th week, compared with the control group, wet weight and water content of feces, and the number of Entero⁃coccus, Bacillus bifidus, Lacticacid bacillus and Bacteroid of feces in HF group were significantly decreased ( P<0.05) , while the pellet number and the Bacillus coli number of feces in HF group were significantly in⁃creased ( P<0.05) . Compared with the HF

  12. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Axel, Anne Marie Dixen; Mikkelsen, Jens D; Hansen, Henrik H

    2010-01-01

    Tesofensine is a novel monoamine reuptake inhibitor that inhibits both norepinephrine, 5-HT, and dopamine (DA) reuptake function. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong effect in obesity management is not cl......Tesofensine is a novel monoamine reuptake inhibitor that inhibits both norepinephrine, 5-HT, and dopamine (DA) reuptake function. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong effect in obesity management...... antagonist), or ritanserin (0.03 mg/kg, 5-HT(2A/C) receptor antagonist). Hence, the mechanism underlying the suppression of feeding by tesofensine in the obese rat is dependent on the drug's ability to indirectly stimulate alpha(1) adrenoceptor and DA D(1) receptor function....

  13. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1.

    Science.gov (United States)

    Moyer, Benjamin J; Rojas, Itzel Y; Kerley-Hamilton, Joanna S; Hazlett, Haley F; Nemani, Krishnamurthy V; Trask, Heidi W; West, Rachel J; Lupien, Leslie E; Collins, Alan J; Ringelberg, Carol S; Gimi, Barjor; Kinlaw, William B; Tomlinson, Craig R

    2016-06-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding specificity

  14. High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats.

    Science.gov (United States)

    Panchal, Sunil K; Poudyal, Hemant; Iyer, Abishek; Nazer, Reeza; Alam, Md Ashraful; Diwan, Vishal; Kauter, Kathleen; Sernia, Conrad; Campbell, Fiona; Ward, Leigh; Gobe, Glenda; Fenning, Andrew; Brown, Lindsay

    2011-05-01

    The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome. PMID:21572266

  15. Pro-Inflammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity

    OpenAIRE

    Wentworth, John M.; Naselli, Gaetano; Brown, Wendy A.; Doyle, Lisa; Phipson, Belinda; Smyth, Gordon K.; Wabitsch, Martin; O'Brien, Paul E.; Harrison, Leonard C.

    2010-01-01

    OBJECTIVE Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity. RESEARCH DESIGN AND METHODS Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs c...

  16. The Herbal Medicine KBH-1 Inhibits Fat Accumulation in 3T3-L1 Adipocytes and Reduces High Fat Diet-Induced Obesity through Regulation of the AMPK Pathway.

    Directory of Open Access Journals (Sweden)

    Ji-Hye Lee

    Full Text Available The aim of this study was to investigate whether a novel formulation of an herbal extract, KBH-1, has an inhibitory effect on obesity. To determine its anti-obesity effects and its underlying mechanism, we performed anti-obesity-related experiments in vitro and in vivo. 3T3-L1 preadipocytes were analyzed for lipid accumulation as well as the protein and gene expression of molecular targets involved in fatty acid synthesis. To determine whether KBH-1 oral administration results in a reduction in high-fat diet (HFD-induced obesity, we examined five groups (n = 9 of C57BL/6 mice as follows: 10% kcal fat diet-fed mice (ND, 60% kcal fat diet-fed mice (HFD, HFD-fed mice treated with orlistat (tetrahydrolipstatin, marketed under the trade name Xenical, HFD-fed mice treated with 150 mg/kg KBH-1 (KBH-1 150 and HFD-fed mice treated with 300 mg/kg KBH-1 (KBH-1 300. During adipogenesis of 3T3-L1 cells in vitro, KBH-1 significantly reduced lipid accumulation and down-regulated the expression of master adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBP β, C/EBP α and peroxisome proliferation-activity receptor (PPAR γ, which led to the suppression of the expression of several adipocyte-specific genes and proteins. KBH-1 also markedly phosphorylated the adenosine monophosphate-activated protein kinase (AMPK and acetyl-CoA carboxylase (ACC. In addition, KBH-1-induced the inhibition effect on lipid accumulation and AMPK-mediated signal activation were decreased by blocking AMPK phosphorylation using AMPK siRNA. Furthermore, daily oral administration of KBH-1 resulted in dose-dependent decreases in body weight, fat pad mass and fat tissue size without systemic toxicity. These results suggest that KBH-1 inhibits lipid accumulation by down-regulating the major transcription factors of the adipogenesis pathway by regulating the AMPK pathway in 3T3-L1 adipocytes and in mice with HFD-induced obesity. These results implicate KBH-1, a

  17. Neuroprotective effects of lomerizine on retinal ganglion cellsin the diet-induced obese C57BL/6J mice%洛美利嗪对膳食诱导的C57BL/6J肥胖小鼠视网膜神经节细胞凋亡的保护作用

    Institute of Scientific and Technical Information of China (English)

    白霞; 赵剑; 赵文青; 陈玉玲

    2014-01-01

    目的:探讨洛美利嗪(LOM)对高脂饮食诱导的C57BL/6J肥胖小鼠视网膜神经节细胞( RGCs)凋亡的保护作用。  方法:小鼠54只随机分为两组,高脂饲料喂养19wk,其中一组同时每天按80 mg/kg给予LOM灌胃。筛选出肥胖组( DIO )和肥胖+洛美利嗪组( DIO+LOM ),对照组(CON)小鼠给予基础饲料。至第19wk末,应用透射电镜观察各组小鼠RGCs的超微结构改变,采用TUNEL法检测各组小鼠RGCs的凋亡情况,并应用激光共聚焦显微镜检测RGCs内钙离子的浓度。  结果:透射电镜结果显示,与CON 组比较, DIO组小鼠RGCs体积变小,细胞质分布紊乱,核染色质发生固缩,而DIO+LOM组小鼠RGCs的形态学改变较DIO组明显减轻。 TUNEL法检测结果显示,与CON组比较, DIO组小鼠GCL层可见较多的凋亡细胞,其细胞凋亡率显著升高( P<0.01),DIO+LOM组RGCs的凋亡率与DIO组比较显著降低( P<0.05)。激光共聚焦结果显示,与CON组比较,DIO组小鼠RGCs内Ca2+荧光染色明显增强,其荧光染色强度比值显著升高( P<0.01),而DIO+LOM组RGCs内Ca2+荧光染色强度较DIO组有明显下降(P<0.01)。  结论:洛美利嗪对肥胖引起的RGCs的损伤和凋亡具有保护作用,其机制可能与减轻细胞内Ca2+超载有关。%AIM: To research the neuroprotective effects of lomerizine ( LOM ) on retinal gangli on cells ( RGCs ) in the diet-induced obeseC57BL/6J mice. METHODS:Fifty-four mice were randomly divided into two groups which were fed a high-fat diet for 19wk.One group mice were lavaged LOM by the dosage of 80mg/kg daily at the same time.The obese mice were selected and divided into diet-induced obesity ( DIO) group, diet-induced obesity and lomerizine (DIO+LOM) group.The mice in the control ( CON) groupw ere fed abasal diet. The ultrastructural changes of RGCs were detected by transmission

  18. CNX-012-570, a direct AMPK activator provides strong glycemic and lipid control along with significant reduction in body weight; studies from both diet-induced obese mice and db/db mice models

    OpenAIRE

    Anil, Tharappel M; Harish, Chandrashekaran; Lakshmi, Mudigere N; Harsha, KrishnaReddy; Onkaramurthy, Mallappa; Sathish Kumar, Venkatesh; Shree, Nitya; Geetha, Venkatachalaiah; Balamurali, Gundalmandikal V; Gopala, Aralakuppe S; Madhusudhan Reddy, Bobbili; Govind, Madabosse K; Anup, Mammen O; Moolemath, Yoganand; Venkataranganna, Marikunte V.

    2014-01-01

    Objectives AMP activated protein kinase (AMPK) regulates the coordination of anabolic and catabolic processes and is an attractive therapeutic target for T2DM, obesity and metabolic syndrome. We report the anti-hyperglycemic and anti-hyperlipidemic effects of CNX-012-570 is an orally bioavailable small molecule (molecular weight of 530 Daltons) that directly activates AMPK in DIO and db/db animal models of diabetes. Methods Activity and efficacy of the compound was tested in cell based as wel...

  19. GPR39, a receptor of the ghrelin receptor family, plays a role in the regulation of glucose homeostasis in a mouse model of early onset diet-induced obesity.

    Science.gov (United States)

    Verhulst, P J; Lintermans, A; Janssen, S; Loeckx, D; Himmelreich, U; Buyse, J; Tack, J; Depoortere, I

    2011-06-01

    GPR39, which may function as a Zn(2+) sensor, is a member of the G protein-coupled receptor family that also includes the receptor for the hunger hormone ghrelin. The down-regulation of GPR39 mRNA in adipose tissue of obese type 2 diabetic patients suggests that GPR39 may contribute to the pathogenesis of the disease. The present study aimed to investigate the role of GPR39 in the regulation of energy balance and glucose homeostasis in wild-type (GPR39(+/+) ) and GPR39 knockout mice (GPR39(-/-) ) with obesity-related type 2 diabetes. GPR39 mRNA levels in adipose tissue of fasted GPR39(+/+) mice fed a high-fat diet (HFD) for 30 weeks were reduced and correlated positively with blood glucose levels. Body weight, fat percentage and energy intake were increased in the HFD group but did not differ between both genotypes. Within the HFD group, blood glucose levels were lower in GPR39(-/-) than in GPR39(+/+) mice, despite significant reductions in prandial plasma insulin levels. The latter may not be a result of changes in β-cell hyperplasia because immunohistochemical staining of pancreata of mice on a HFD showed no differences between genotypes. The lower blood glucose levels may involve alterations in insulin sensitivity as revealed by glucose tolerance tests and respiratory quotient measurements that showed a preference of obese GPR39(-/-) mice for the use of carbohydrates as metabolic fuel. The increase in plasma ghrelin levels in GPR39(-/-) mice fed a HFD may contribute to the alterations in glucose homeostasis, whereas changes in gastric emptying or intestinal Zn(2+) absorption are not involved. The results obtained in the present study suggest that GPR39 plays a role in the pathogenesis of obesity-related type 2 diabetes by affecting the regulation of glucose homeostasis. PMID:21470317

  20. Effect of sodium butyrate on diet-induced obesity in the Sprague-Dawley rat%丁酸钠对饮食诱导肥胖大鼠的作用

    Institute of Scientific and Technical Information of China (English)

    朱涵; 谭莎莎; 杨虹; 王凌

    2015-01-01

    Summary Obesity has been reported as an increasingly prevalent and highly heritable health problem leading to increased risks for several common diseases . Human obesity can be induced by genetic factors such as loss‐of‐function mutations in individual genes . The products of these genes are essential for normal body mass regulation in both laboratory animals and humans . Nevertheless , the role of gene‐environment interactions in the etiology of obesity cannot be ignored . Diet is a major factor of our current obesogenic environment , and the interests have been aroused in rodent models of diet‐induced obesity (DIO) . The SD (Sprague‐Dawley) rat model of DIO was been reported to exhibit a clear segregation into susceptible and resistant subpopulations shortly after being transferred to a high energy diet . We established the obesity‐susceptible ( OS) and obesity‐resistant ( OR) rat model and examined the effect of butyric acid , a short chain fatty acid formed by fermentation in the large intestine , in the regulation of obesity in mice fed a high‐fat diet . Male SD rats were divided into OS rats and OR rats after being fed with high fat diet for three weeks . Then both of them were fed with high fat diet for another 12 weeks . Measurements of body mass , body length , Lee�s index , and body mass index (BMI) were performed . After the rats were sacrificed , body fat content , serum total cholesterol ( TC ) , triglyceride ( TG ) , high density lipoprotein ( HDL ) , low density lipoprotein ( LDL) and serum leptin were measured . The results showed that there were significant differences in body mass , BMI , body fat content , TC , TG , LDL and serum leptin between OS rats and control rats . But there were no significant differences between OR rats and control rats . In the OS rats , sodium butyrate was administrated in the high‐fat diet at the concentration of 8 mmol/L for 16 weeks . Body mass , body length , Lee�s index , BMI , body fat

  1. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    Science.gov (United States)

    van Drongelen, Joris; van Koppen, Arianne; Pertijs, Jeanne; Gooi, Jonathan H; Parry, Laura J; Sweep, Fred C G J; Lotgering, Frederik K; Smits, Paul; Spaanderman, Marc E A

    2012-03-01

    Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a reduction in arterial diameter. In this study, we tested the hypothesis that local vascular responses to relaxin are impaired in diet-induced overweight female rats on a high-fat cafeteria-style diet for 9 wk. Rats were chronically infused with either relaxin or placebo for 5 days, and vascular responses were measured in isolated mesenteric arteries and the perfused kidney. Diet-induced overweight significantly increased sensitivity to phenylephrine (by 17%) and vessel wall thickness, and reduced renal perfusion flow (RPFF; by 16%), but did not affect flow-mediated vasodilation, myogenic reactivity, and vascular compliance. In the normal weight rats, relaxin treatment significantly enhanced flow-mediated vasodilation (2.67-fold), decreased myogenic reactivity, and reduced sensitivity to phenylephrine (by 28%), but had no effect on compliance or RPFF. NO blockade by l-NAME diminished most relaxin-mediated effects. In diet-induced overweight rats, the vasodilator effects of relaxin were markedly reduced for flow-mediated vasodilation, sensitivity to phenylephrine, and myogenic response compared with the normal diet rats, mostly persistent under l-NAME. Our data demonstrate that some of the vasodilator responses to in vivo relaxin administration are impaired in isolated mesenteric arteries and the perfused kidney in diet-induced overweight female rats. This does not result from a decrease in Rxfp1 (relaxin family peptide receptor) expression but is likely to result from downstream disruption to endothelial-dependent mechanisms in diet-induced overweight animals. PMID:22174401

  2. Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

    Directory of Open Access Journals (Sweden)

    Oosterveer Maaike H

    2011-12-01

    Full Text Available Abstract Background Overactivity and/or dysregulation of the endocannabinoid system (ECS contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1 in adipocyte function and CB1-receptor deficient (CB1-/- mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown. Methods We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB1-/- and CB1+/+ mice fed a high-fat (HF or a high-fat/fish oil (HF/FO diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB1 functioning. Results The adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL activities were also not altered in CB1-/- mice. Conclusions These findings indicate that protection against diet-induced adiposity in CB1-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.

  3. Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

    Science.gov (United States)

    Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

  4. AQP7 expression in high-fat diet induced obesity prone and obesity resistant rats%水甘油通道蛋白7在肥胖易感和肥胖抵抗大鼠脂肪组织的表达

    Institute of Scientific and Technical Information of China (English)

    王晓珂; 赵健亚; 刘天娥; 张璇; 吴俊霞; 王春; 陈刚

    2013-01-01

    Objective:To establish high fat diet induced obesity prone and obesity resistant rats and investigate the AQP7 expression in white adipose tissue in each group. Methods: six-week-old outbred male SD rats were randomly di-vided into two groups: the high-fat diet group (HF, n=24) and the chow food group (C, n=10). After 8 weeks, rats in HF group were designated as OP and OR rats. Insulin sensitivity was determined by oral glucose tolerance test. AQP7 mRNA expression was detected by Real time Polymerase Chain Reaction (RT-PCR). Results:Among OP , OR group and C group, body weights were (556.8±10.6), (478.9±8.9) and (470.5±8.6)g, (P<0.05 );body fat was (6.47±0.48), (4.53±0.43) and (3.34± 0.28)%, (P<0.05);Serum TC was (1.43±0.14), (1.15±0.10) and (1.17±0.15), (P<0.05);TG was (0.78±0.13), (0.62±0.04) and (0.51 ±0.08), (P<0.05); Insulin was (66.09 ±8.06), (48.03 ±8.70) and (29.57 ±6.94), (P<0.05); HOMA-IR was (19.63 ±3.08), (14.74±9.51) and (8.08±0.81), (P<0.05); AQP7 mRNA expression in white adipose tissue was (3.80±0.38), (1.12±0.15) and (1.00±0.00), (P<0.05). Conclusion: AQP7 mRNA expression in white adipose tissue is closely related to high-fat diet in-duced obesity.%目的:探讨水甘油通道蛋白7与高脂膳食诱导的大鼠肥胖的关系。方法:雄性6周龄SD大鼠随机分为高脂饲料组24只,普通饲料组10只。8周后将高脂饲料组大鼠分为饮食诱导肥胖组(OP)和饮食诱导肥胖抵抗组(OR)大鼠,口服葡萄糖耐量实验检测各组大鼠的胰岛素敏感性。实验结束分离大鼠的肾周和睾周脂肪组织并准确称重,分离血清测定血糖血脂。实时荧光定量PCR技术检测大鼠脂肪组织AQP7的mRNA表达。结果:OP组大鼠体重(556.8±10.6)g、体脂(6.47±0.48)%、TC(1.43±0.14)mmoL/L、TG(0.78±0.13)mmoL/L、Insulin含量(66.09±8.06)μIU/mL和HOMA-IR (19.63±3.08)。显著高于OR组的(478.9±8.9)g、(4.53±0.43)%、(1.15±0.10

  5. Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue

    OpenAIRE

    Hoffmann, Linda S.; Etzrodt, Jennifer; Willkomm, Lena; Sanyal, Abhishek; Scheja, Ludger; Fischer, Alexander W.C.; Stasch, Johannes-Peter; Bloch, Wilhelm; Friebe, Andreas; Heeren, Joerg; Pfeifer, Alexander

    2015-01-01

    Obesity is characterized by a positive energy balance and expansion of white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) combusts energy to produce heat. Here we show that a small molecule stimulator (BAY 41-8543) of soluble guanylyl cyclase (sGC), which produces the second messenger cyclic GMP (cGMP), protects against diet-induced weight gain, induces weight loss in established obesity, and also improves the diabetic phenotype. Mechanistically, the haeme-dependent sGC stimu...

  6. Expression of GnRH in the hypothalamic arcuate nucleus in rats with diet-induced obesity and its influence on spermatogenesis%营养性肥胖大鼠弓状核促性腺激素释放激素的表达变化以及对精子发生的影响

    Institute of Scientific and Technical Information of China (English)

    刘冉冉; 赵方欣; 张洪芹

    2013-01-01

    Objective:To investigate the expressions of neuropeptide Y (NPY), obesity receptor (ob-R) and gonadotropin-re-leasing hormone (GnRH) in the hypothalamic arcuate nucleus in rats with diet-induced obesity and its influence on spermatogenesis. Methods:Weanling SD male rats were fed with high-energy feed. After 14 weeks, obesity models were selected according to Lee's Index. The rats in the control group were established by feeding them with normal feed. We observed the expressions of NPY. ob-R and GnRH in the hypothalamic arcuate nucleus and the expression of androgen binding protein (ABP) in the testis and the changes of spermatogenic cells cycle with obesity. We also detected the level of leptin,follicule-stimula-ting hormone (FSH), luteinizing hormone (LH) in serum and the concentration of testosterone in venous blood of testicle. Results:The level of leptin was higher in the obesity group than in the control group. The levels of testosterone, FSH and LH were lower than that in the control group. The expression of NPY increased, and the expressions of ob-R and GnRH decreased, as compared with the control group. The expression of ABP in testicles in obesity models was attenuated. The spermatogenic cells in S phase in obesity model decreased, while the cells in G2/M phase significantly increased. Conclusion:The low level of GnRH induced by neuroendocrine metabolic disorder lead to dysfunction of hypothalamic-pituitarytesticular axis, resulting in impediment of spermatogenesis, which might result in infertility.%目的:探讨营养性肥胖大鼠弓状核神经肽Y(NPY)、瘦素受体(ob-R)及与生殖相关的促性腺激素释放激素(GnRH)表达变化以及对精子发生的影响.方法:免疫组织化学观察NPY、ob R及GnRH在肥胖模型组下丘脑弓状核的表达情况以及睾丸支持细胞雄激素结合蛋白(ABP)表达变化;流式细胞分析检测睾丸生精细胞周期的改变.并测定血清中瘦素、睾酮、卵泡

  7. Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes

    DEFF Research Database (Denmark)

    Bartels, E D; Bang, C A; Nielsen, L B

    2009-01-01

    median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice. CONCLUSIONS: Our findings suggest that diet-induced type 2 diabetes causes early......BACKGROUND: Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia. MATERIALS AND METHODS: The effect of obesity and type 2 diabetes on the development of...

  8. Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

    OpenAIRE

    Oosterveer, Maaike H.; Koolman, Anniek H; de Boer, Pieter T; Bos, Trijnie; Bleeker, Aycha; Bloks, Vincent W.; Kuipers, Folkert; Sauer, Pieter J. J.; van Dijk, Gertjan

    2011-01-01

    Background: Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown. Methods: We evaluated adipose tissue differentiation/proliferation markers and q...

  9. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

    Science.gov (United States)

    van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state. PMID:26824042

  10. 白藜芦醇对小鼠营养性肥胖伴生殖功能损害的作用%Role of resveratrol in diet-induced obesity and reproductive insufficiency in mice

    Institute of Scientific and Technical Information of China (English)

    孟春燕; 蔡翔宇; 白婷; 李宏博; 李静; 唐向东

    2013-01-01

    目的 探讨白藜芦醇对肥胖性不育的防治作用.方法 36只雌性昆明小鼠按随机区组法分为3组(对照组、高脂组和干预组),每组12只,分别喂以正常饮食、高脂饮食和高脂饮食加白藜芦醇.分别在4周、8周和12周时监测动物体重、空腹血糖和糖耐量情况.喂养12周后检测小鼠空腹胰岛素、血清雌二醇、黄体生成素、睾酮水平,以阴道脱落细胞判断小鼠动情周期,以雌、雄个体3:1的比例进行交配,观察小鼠生育能力.结果 喂养12周后高脂组和干预组小鼠体重[(61.52±6.92),(63.06 ±5.80)g]都明显高于对照组[(47.76±5.02)g],差异具有统计学意义(P<0.05);而干预组体重相对于高脂组差异没有统计学意义(P>0.05).高脂组空腹血糖[(6.98±0.33)mmol/L]和空腹胰岛素[(38.02 ±7.21) μIU/L]明显高于对照组[(5.30±0.36) mmol/L,(30.29±5.58)μIU/L],差异均具有统计学意义(P<0.05);干预组空腹血糖[(5.45 ±0.67) mmol/L]和空腹胰岛素[(30.21 ±4.60)μIU/L]与高脂组相比明显下降,且差异均具有统计学意义(P<0.05).性激素分析显示高脂组雌二醇[(5.67 ±0.98) ng/L]与黄体生成素[(0.346±0.025) IU/L]较对照组[(3.007 ±0.721) ng/L,(0.202 ±0.041) IU/L]明显升高(P<0.05);干预组雌二醇[(2.115 ±0.353)ng/L]和黄体生成素[(0.245 ±0.041) IU/L]与高脂组相比明显下降,差异均具有统计学意义(P<0.05).睾酮含量各组之间没有统计学差异.高脂饮食还导致动情周期紊乱甚至消失,卵巢组织学显示高脂饮食导致闭锁卵泡数量明显增加.结论 高脂饮食能够诱导雌性小鼠肥胖、代谢综合征与生殖功能损害,白藜芦醇对此能起到一定缓解作用.%Objective To investigate the role of reserveratrol in rescue of obesity-induced infertility.Methods According to randomized block design,thirty-six female Kunming mice were randomly divided into three groups (control group,high-fat group and treatment

  11. Region-Specific Diet-induced and Leptin-Induced Cellular Leptin Resistance Includes the Ventral Tegmental Area in Rats

    OpenAIRE

    Matheny, M.; Shapiro, A.; Tümer, N.; Scarpace, P. J.

    2010-01-01

    Diet-induced obesity (DIO) results in region-specific cellular leptin resistance in the arcuate nucleus (ARC) of the hypothalamus in one strain of mice and in several medial basal hypothalamic regions in another. We hypothesized that the ventral tegmental area (VTA) is also likely susceptible to diet-induced and leptin-induced leptin resistance in parallel to that in hypothalamic areas. We examined two forms of leptin resistance in F344xBN rats, that induced by 6-months of high fat (HF) feedi...

  12. Feasibility of simultaneous PET/MR in diet-induced atherosclerotic minipig

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Ludvigsen, Trine P; Johannesen, Helle H;

    2014-01-01

    Novel hybrid 18-fluoro-deoxy-D-glucose ((18)F-FDG) based positron emission tomography (PET) and magnetic resonance imaging (MRI) has shown promise for characterization of atherosclerotic plaques clinically. The purpose of this study was to evaluate the method in a pre-clinical model of diet-induc...

  13. Efeito do chá verde (Camelia sinensis em ratos com obesidade induzida por dieta hipercalórica Antiobesity effects of green tea (Camelia sinensis in high caloric diet-induced obese rats

    Directory of Open Access Journals (Sweden)

    Marta Vera-Cruz

    2010-10-01

    Full Text Available INTRODUÇÃO: A obesidade é fator de risco para várias doenças. Estudos têm demonstrado que os polifenóis do chá verde auxiliam na perda de peso e interferem nos mecanismos de diversas doenças. A insulina, agindo por meio de seu receptor (IR, desencadeia uma série de respostas. A via IR/Shc é ligada ao crescimento celular e à mitogênese. OBJETIVOS: Estudar o efeito do chá verde no peso corporal e no teste de tolerância à glicose (GTT. No fígado, estudar a fosforilação do IR, a presença e a expressão de IR e Shc e suas alterações morfológicas. MATERIAL E MÉTODOS: Ratos Wistar, jovens e tratados com dieta hipercalórica ou dieta própria para ratos, foram submetidos a tratamento com chá verde. Para retirada do fígado, após anestesia, foi infundida insulina ou solução salina. Para avaliar o grau de fosforilação do IR, o fragmento foi homogeneizado e submetido a técnicas de imunoprecipitação e imunoblotting. Para análise morfológica, foi utilizada a técnica de coloração por hematoxilina e eosina e para localizar a presença de IR e Shc, técnica de imuno-histoquímica. RESULTADOS E CONCLUSÃO: Observamos diminuição do peso corporal e da esteatose no fígado e melhora no GTT. Houve aumento da fosforilação do IR no fígado dos animais obesos tratados com relação aos obesos não submetidos a tratamento. Verificaram-se lesões que poderiam ser associadas ao tratamento, como necrose focal. A análise imuno-histoquímica demonstrou presença de IR e Shc em todos os grupos estudados e sugeriu alterações na expressão de IR e Shc nos grupos obesos e obesos tratados.INTRODUCTION: Obesity is a risk factor for several diseases. Studies have shown that polyphenols in green tea aid in weight loss and influence the mechanisms of several diseases. Insulin, acting through its receptor (IR, triggers a series of responses. IR/Shc pathway is linked to cell growth and mitogenesis. OBJECTIVES: To investigate the effect of

  14. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance

    DEFF Research Database (Denmark)

    Madsen, Lise; Guerre-Millo, Michéle; Flindt, Esben N;

    2002-01-01

    Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration...... completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA in the...... ranking order PPARalpha > PPARdelta > PPARgamma. Expression of PPARgamma target genes in adipose tissue was unaffected by TTA treatment, whereas the hepatic expression of PPARalpha-responsive genes encoding enzymes involved in fatty acid uptake, transport, and oxidation was induced. This was accompanied...

  15. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.

    Science.gov (United States)

    Ringling, Rebecca E; Gastecki, Michelle L; Woodford, Makenzie L; Lum-Naihe, Kelly J; Grant, Ryan W; Pulakat, Lakshmi; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis. PMID:27583382

  16. Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

    Science.gov (United States)

    Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

    2012-01-01

    Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

  17. Perilipin overexpression in mice protects against diet-induced obesity

    OpenAIRE

    Miyoshi, Hideaki; Souza, Sandra C.; Endo, Mikiko; Sawada, Takashi; Perfield, James W.; Shimizu, Chikara; Stancheva, Zlatina; Nagai, So; Strissel, Katherine J.; Yoshioka, Narihito; Obin, Martin S.; Koike, Takao; Greenberg, Andrew S.

    2010-01-01

    Perilipin A is the most abundant phosphoprotein on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced catecholamine-stimulated lipolysis, and increased insulin resistance. To understand the physiological consequences of increased perilipin expression in vivo, we generated transgenic mice that overexpressed either human or mouse perilipin using the adipocyte-specific aP2 promoter/en...

  18. Perilipin overexpression in mice protects against diet-induced obesity

    Science.gov (United States)

    Perilipin A is the most abundant phosphoprotein on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced catecholamine-stimulated lipolysis, and increased insulin resistance. To understand t...

  19. 蓝莓花青素对肥胖大鼠血脂、血清炎性因子及胰岛素敏感性的影响%Effects of blueberry anthocyanidin on dyslipidemia, proinflammatory cytokines and insulin sensitivity in high-fat-diet induced obese rats

    Institute of Scientific and Technical Information of China (English)

    余仁强; 马路一; 朱静; 周详; 吴小优; 靳姗姗; 昌维维; 宋晓彤

    2014-01-01

    Objective To investigate the effect of blueberry anthocyanidin on serum lipid profiles,proinflammatory cytokines and insulin sensitivity in high-fat-diet induced obese rats.Methods Male Sprague-Dawley rats were randomly grouped to receive a standard chow diet (control group,7 cases) or high-fat-diet (23 cases).Six weeks later,high-fat-diet induced obese rats were divided into the 2 groups.Then,rats received a standard chow diet,a high-fat-diet,or a high-fat-diet supplemented with anthocyanidin extracted from blueberry at 200 mg/(kg · d) for 4 weeks,and were then euthanized.Parameters of body weight,visceral adipose tissue,serum glucose,insulin,total cholesterol(TC),triglyceride (TG),low-density lipoprotein (LDL),high-density lipoprotein (HDL),tumor necrosis factor-or (TNF-α),interleukin-6(IL-6),high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment insulin resistance (HOMR-IR) were measured.Results The levels of glucose [(9.15 ± 1.10) mmol/L],TC[(462.5 ± 81.5) mg/L],TG[(152.5 ±19.1) mg/L],LDL[(203.7 ±31.1) mg/L],TNF-α[(4.03 ± 1.03) ng/L],IL-6[(1.81 ±0.31) ng/L],hs-CRP[(106.62 ± 15.52) ng/L] and HOMA-IR (3.94 ± 0.78)in blueberry anthocyanidin group were lower than those in the obese rats [(11.38 ± 1.50) mmol/L,(566.2 ± 113.2) mg/L,(192.5 ± 24.9) mg/L,(253.7 ± 58.3)mg/L,(5.74 ± 1.61) ng/L,(3.85 ±0.93) ng/L,(132.62 ± 17.18) ng/L,5.09 ±O.90],and the differences were significant(all P < 0.05).But the levels of the parameters in blueberry anthocyanidin group were higher than the control group [(7.52±1.37) mmol/L,(377.1 ±71.3) mg/L,(124.2 ±26.3) rng/L,(135.7 ±38.2) rng/L,(2.41 ±0.42)ng/L,(1.12 ±0.46) ng/L,(72.28 ±12.11) ng/L,2.41 ±0.23],and the differences were significant(all P <0.05).The level of HDL in blueberry anthocyanidin group [(126.2 ± 38.1) mg/L] was higher than that in obese group [(95.0 ±25.6 mg/L)],but the level of HDL in blueberry anthocyanidin group was lower than that in the control group [(165.7 ± 22

  20. Synthetic FXR Agonist GW4064 Prevents Diet-induced Hepatic Steatosis and Insulin Resistance

    OpenAIRE

    MA, YONGJIE; Huang, Yixuan; Yan, Linna; Gao, Mingming; Liu, Dexi

    2013-01-01

    The nuclear receptor farnesoid X receptor (FXR), an endogenous sensor for bile acids, plays an important role in cholesterol, lipid and carbohydrate metabolism. The objective of this study is to examine the effect of FXR activation on diet-induced obesity and hepatic steatosis. Activation of FXR by its synthetic agonist, 3-[2-[2-Chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid (GW4064), suppressed weight gain in C57BL/6 mice fed with either ...

  1. Intestinal GATA4 deficiency protects from diet-induced hepatic steatosis

    OpenAIRE

    Patankar, Jay V.; Obrowsky, Sascha; Doddapattar, Prakash; Hoefler, Gerald; Battle, Michele; Levak-Frank, Sanja; Kratky, Dagmar

    2012-01-01

    Background & Aims GATA4, a zinc finger domain transcription factor, is critical for jejunal identity. Mice with an intestine-specific GATA4 deficiency (GATA4iKO) are resistant to diet-induced obesity and insulin resistance. Although they have decreased intestinal lipid absorption, hepatic de novo lipogenesis is inhibited. Here, we investigated dietary lipid-dependent and independent effects on the development of steatosis and fibrosis in GATA4iKO mice. Methods GATA4iKO and control mice were f...

  2. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

    OpenAIRE

    Maharshi Bhaswant; Hemant Poudyal; Mathai, Michael L.; Ward, Leigh C.; Peter Mouatt; Lindsay Brown

    2015-01-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular ...

  3. Efeitos do exercício físico na expressão e atividade da AMPKα em ratos obesos induzidos por dieta rica em gordura Effects of physical exercise in the Ampkα expression and activity in high-fat diet induced obese rats

    Directory of Open Access Journals (Sweden)

    José Rodrigo Pauli

    2009-04-01

    Full Text Available INTRODUÇÃO: A ingestão de dieta hiperlipídica é um fator de risco singular no desenvolvimento de resistência à insulina e diabetes do tipo 2. OBJETIVO: O estudo investigou os efeitos do exercício físico na expressão e atividade da AMPKα em ratos obesos. MÉTODOS: Foram utilizados ratos Wistar, aleatoriamente divididos em quatro grupos, que receberam dieta padrão de manutenção (grupo controle ou dieta hiperlipídica (DHL (grupos sedentários e exercitados, por período de quatro meses. Dois diferentes protocolos de exercícios foram utilizados: exercício agudo ou crônico de natação. O teste de tolerância à insulina foi realizado para estimar a sensibilidade à insulina. Os níveis protéicos da AMPKα e do GLUT4 e também de p-AMPKα e pACC no músculo esquelético dos ratos foram determinados através da técnica de Western blot. RESULTADOS: O teste de tolerância à insulina revelou significativo prejuízo na ação da insulina após a alimentação com a DHL, indicando insulino-resistência quando comparado com grupo controle (p INTRODUCTION: High-fat diet is a special risk factor in the development of insulin resistance and type 2 diabetes. OBJECTIVE: To investigate the effects of physical exercise on the AMPK expression and activity in high-fat diet induced obese rats. METHODS: Wistar rats were randomly divided into four groups and received either a rat maintenance diet (control group or an isocaloric high-fat diet (HFD (sedentary groups and exercised groups for four months. Two different exercise protocols were utilized: acute or chronic swimming exercise. Insulin tolerance test was performed to estimate whole-body insulin sensitivity. AMPKα and GLUT4 as well as p-AMPKα and pACC of rats' skeletal muscle levels were determined using Western blot. RESULTS: Insulin tolerance test revealed a significantly impaired insulin action after HFDt feeding, indicating high-fat induced insulin resistance when compared to control

  4. Transgenic Rescue of Adipocyte Glucose-dependent Insulinotropic Polypeptide Receptor Expression Restores High Fat Diet-induced Body Weight Gain

    DEFF Research Database (Denmark)

    Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria;

    2011-01-01

    The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and...... the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression...... targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass...

  5. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E

    OpenAIRE

    Yinhua Ni; Mayumi Nagashimada; Fen Zhuge; Lili Zhan; Naoto Nagata; Akemi Tsutsui; Yasuni Nakanuma; Shuichi Kaneko; Tsuguhito Ota

    2015-01-01

    Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese ...

  6. Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice

    OpenAIRE

    Fukumitsu, S.; Aida, K; Ueno, N; Ozawa, S.; Takahashi, Y.; Kobori, M

    2008-01-01

    Flaxseed lignan secoisolariciresinol diglucoside (SDG) has been reported to prevent and alleviate lifestyle-related diseases including diabetes and hypercholesterolaemic atherosclerosis. This study assesses the effect of SDG on the development of diet-induced obesity in mice and the effect of the SDG metabolite enterodiol (END) on adipogenesis in 3T3-L1 adipocytes. We compared body weight, visceral fat weight, liver fat content, serum parameters, mRNA levels of lipid metabolism-related enzyme...

  7. Characterization of Obesity Phenotypes in Psammomys Obesus (Israeli Sand Rats)

    OpenAIRE

    Walder, Ken R.; Fahey, Richard P.; Morton, Greg J.; Zimmet, Paul Z.; Collier, Greg R

    2000-01-01

    Psammomys obesus (the Israeli sand rat) has been well studied as an animal model of Type 2 diabetes. However, obesity phenotypes in these animals have not been fully characterized. We analyzed phenotypic data including body weight, percentage body fat, blood glucose and plasma insulin concentration for over 600 animals from the Psammomys obesus colony at Deakin University to investigate the relationships between body fat, body weight and Type 2 diabetes using regression analysis and general l...

  8. Changes in global DNA methylation and the effects of n-3 polyunsaturated fatty acids in diet-induced obese mice%肥胖小鼠DNA甲基化改变以及n-3多不饱和脂肪酸的影响作用

    Institute of Scientific and Technical Information of China (English)

    申文雯; 樊超男; 夏露露; 王翠; 董华; 齐可民

    2012-01-01

    ,the rates of global DNA methylation in adipose tissue were significantly increased in the two groups of diet-induced obese (DIO) mice. If the two groups of DIO mice were, compared, the n-3 PUFAs in diets had inhibitory effects on the global DNA methylation. The expressions of DNMT1 ,DNMT3a and DNMT3b in the adipose tissue were higher in DIO mice fed the n-6 PUFAs diet compared to the normal-fat diet, whereas no changes were shown in the expression of these DNMTs in DIO mice fed the n-3 PUFAs diet. [Conclusion] The global DNA methylation in the adipose tissue of obesity increases and dietary fish oil n-3 PUFAs have inhibitory effects on DNA methylation.

  9. A low-fat diet has a higher potential than energy restriction to improve high-fat diet-induced insulin resistance in mice

    NARCIS (Netherlands)

    Muurling, M.; Jong, M.C.; Mensink, R.P.; Hornstra, G.; Dahlmans, V.E.H.; Pijl, H.; Voshol, P.J.; Havekes, L.M.

    2002-01-01

    Previous studies have shown that energy restriction (ER) or low-fat (LF) diets have beneficial effects on high-fat (HF) diet-induced obesity and non-insulin-dependent diabetes. However, comparison between ER and low-fat diet regarding the effect on insulin resistance and lipid metabolism has not bee

  10. 高脂膳食诱导肥胖并影响脂肪组织MCHR1和OB-Rb的表达%High fat diet induces obesity and alters the expression of MCHR1 and OB-Rb in the adipose tissue

    Institute of Scientific and Technical Information of China (English)

    李金容; 闫剑群; 陈坷; 王倩; 赵小林; 张嫄

    2011-01-01

    Objective To investigate the effect of high-fat (HF) diet on the body weight and the mRNA expression of melanin concentrating hormone receptor 1 ( MCHR1) and leptin receptor ( OB-Rb) in the adipose tissue in rats, the two important and opposite factors in regulating the body weight. Methods Post-weaning rats were divided into 3 groups: the NC group were fed a normal-chow diet (NC) (13% calories from fat), the HF group with a HF-diet (47% calories from fat) and the PHF group pair-fed a HF-diet (47% calories from fat). At the end of 8th week, the gained bodyweight, the plasma melanin concentrating hormone (MCH) and leptin, and the expression levels of MCHR1 and OB-Rb in the adipose tissue were measured. Results Both the HF-diet and pair-fed HF-diet enhanced the body weight (P 0.05). Conclusion Chronic intake of iso-caloric HF-diet and ad libitum HF-diet obviously results in increase in the body weight, serum leptin, and MCH concentration. Diet-induced obesity and related metabolic disorders are possibly correlated with up-regulated expression of MCHR.1 and down-regulated expression of OB-Rb in the adipose tissue.%目的:比较不同方式高脂饮食对大鼠脂肪组织黑色素聚集激素受体1(melanin concentrating hormone receptor 1,MCHR1)和瘦素受体(OB-Rb)表达的影响.方法:断乳大鼠分成3组:正常膳食组(NC组,13%热卡来自脂肪),与正常膳食组等热量的高脂膳食组(PHF组,47%热卡来自脂肪)及自由摄入高脂膳食组(HF组,47%热卡来自脂肪).喂养8周后,称量大鼠体质量,检测血清中的黑色素聚集激素(melanin concentrating hormone,MCH)和瘦素(leptin)浓度.运用实时定量PCR检测脂肪组织的MCHRl和OB-Rb mRNA水平.结果:HF组和PHF组体质量显著高于NC组(P<0.01),血清中MCH和leptin浓度较NC组有明显增高( MCH,P<0.01;leptin,P<0.05).同对照组相比,HF组和PHF组脂肪组织中的MCHRl mRNA水平显著升高(P<0.05),而OB-Rb mRNA却显著降低(HF组,P<0.01

  11. High fat diet induced disturbances of energy metabolism

    NARCIS (Netherlands)

    Berg, Sjoerd Adrianus Antonius van den

    2010-01-01

    Obesity and insulin resistance (IR) are multifactorial pathologies, characterized by a complex etiology. In addition to genetics, age and sex, environmental factors such as dietary composition and lifestyle have profound effects on the development of both pathologies. Excess dietary energy intake (E

  12. Effect of Ginseng (Panax ginseng) Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement

    OpenAIRE

    Chang Hyeon Park; Seon Kyeong Park; Tae Wan Seung; Dong Eun Jin; Tianjiao Guo; Ho Jin Heo

    2015-01-01

    High-fat diet-induced obesity leads to type 2 diabetes. Recently, there has been growing apprehension about diabetes-associated cognitive impairment (DACM). The effect of ginseng (Panax ginseng) berry ethyl acetate fraction (GBEF) on mice with high-fat diet-induced cognitive impairment was investigated to confirm its physiological function. C57BL/6 mice were fed a high-fat diet for 5 weeks and then a high-fat diet with GBEF (20 and 50 mg/kg of body weight) for 4 weeks. After three in vivo beh...

  13. Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor

    OpenAIRE

    Hirose, Mai; Ando, Taishi; Shofiqur, Rahman; Umeda, Kouji; Kodama, Yoshikatsu; Van Nguyen, Sa; Goto, Tsuyoshi; Shimada, Masaya; Nagaoka, Satoshi

    2013-01-01

    Background There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model. Methods We determined the inhibitory action of Anti-lipase IgY on lipas...

  14. n-3多不饱和脂肪酸对肥胖小鼠食欲调节因子表达的影响%Dietary n-3 PUFAs affect the mRNA expression of satiety regulators in diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    刘新丽; 樊超男; 申文雯; 田春雨; 齐可民

    2011-01-01

    [目的]探讨n-3多不饱和脂肪酸(n-3 PUFAs)对饲料诱导肥胖小鼠食欲调节因子表达的影响.[方法]使用3~4周龄C57BL/6J雄性小鼠,随机分为3组,每组15只,分别给予两种高脂饲料(脂肪含量为34.9%,供能比为60%)-n-6PUFAs(来源于葵花籽油)饲料和n-3PUFAs(来源于鱼油)饲料喂养3个月;以正常脂饲料(脂肪含量为4.3%,供能比为10%)作为诱导肥胖鼠的对照.小鼠禁食12 h后,麻醉状态下心脏取血、脑和性腺周围脂肪.血浆瘦素含量测定采用酶联免疫分析法;脂肪组织瘦素及下丘脑瘦素受体、神经肽Y(NPY)和促阿片-黑素细胞皮质素原(POMC)mRNA表达采用实时荧光定量PCR进行.[结果]两组高脂饲料诱导的肥胖小鼠体重和血浆瘦素浓度均高于正常脂饲料组小鼠,但n-3PUFAs高脂饲料组肥胖小鼠在两项指标的增高程度显著低于n-6PUFAs高脂饲料组肥胖小鼠.与正常脂饲料喂养小鼠相比,n-6PUFAs高脂饲料诱导肥胖小鼠脂肪组织瘦素和下丘脑瘦素受体、POMC mRNA表达水平显著升高,而NPY mRNA水平降低;n-3PUFAs高脂饲料诱导肥胖小鼠的上述4种基因mRNA表达则未发生变化.[结论]n-3PUFAs可减轻肥胖状态下瘦素及其受体、NPY、POMC等食欲调节因子表达的异常,在肥胖发生中起着积极作用.%[Objective] To investigate the effects of n-3 polyunsaturated fatty acids(n-3 PUFAs) on the mRNA expression of satiety regulators in diet-induced obese (DIO) mice. [Methods] Three to four-week-old male C57BL/6J mice were randomly divided into 3 groups with 15 cases in each group. There mice were fed with two types of high-fat diet (34. 9% fat providing 60% of total energy) with n-6 PUFAs(originated from sunflower oil) and n-3 PUFAs(originated from fish oil) respectively to induce obesity, with a normal-fat diet(4.3% fat providing 10% of total energy) as lean control. After fasted for 12 hours, blood samples were drawn, and brains and epididymal fat

  15. High fat diet-induced obese rats and diabetic rats: a comparative study of glucose and lipid metabolism%高糖高脂饲料诱导的肥胖大鼠和糖尿病大鼠糖脂代谢对比分析

    Institute of Scientific and Technical Information of China (English)

    李娟; 邹大进; 冯正康

    2012-01-01

    Objective To compare the glucose and lipid metabolism between high sucrose plus high fat diet-induced obese rats and diabetic rats prepared with the same feed combined with low-dose streptozotocin. Methods Six to eight weeks old SD rats were randomly divided into normal control group and high fat group, fed with normal diet and high sucrose plus high fat diet for 8 weeks, respectively. Eight weeks later HF group was further randomized into two groups: one is diabetic mellitus group(DM group) injected with low dose streptozotocin (30 mg/kg). The other is obese groupCOB group). The animals were maintained on their diet and were observed for 4 weeks. The body weight, blood glucose, triglyceride, total cholesterol, fasting insulin, insulin sensitivity were examined. Intraperitoneal glucose tolerance test (IPGTT) and insulin release test were also performed. Results After treatment with high fat diet plus STZ injection, DM group gradually developed symptoms of excessive food & water consumption, polyuria and weight loss. At the end of the 12th week, the fasting blood glucose of DM group was significantly higher than that of the OB group (P<0. 01 ) and the insulin sensitivity was significantly lower than that of the OB group (P<0. 01 ). The rats of OB group presented impaired glucose tolerance and impaired insulin secretion, and DM group had more severely impaired glucose tolerance and impaired insulin secretion; and the serum total cholesterol, triglyceride levels in DM group were significantly higher than those in the OB group (P< 0. 01 ). Conclusion Continuous high sucrose-high fat diet can induce impaired glucose regulation, insulin secretion dysfunction and lipid metabolism disorders; high fat combined with STZ injection can further aggravate these disorders.%目的 对比分析高糖高脂饲料诱导的肥胖大鼠和相同饲料联合小剂量链脲佐菌素( STZ)制备的糖尿病大鼠糖脂代谢特点.方法 雄性SD大鼠随机分为正常组(NC组)

  16. Amelioration of diet-induced diabetes mellitus by removal of visceral fat.

    Science.gov (United States)

    Pitombo, Cid; Araújo, Eliana P; De Souza, Cláudio T; Pareja, José C; Geloneze, Bruno; Velloso, Lício A

    2006-12-01

    The effect of visceral fat removal upon glucose homeostasis, insulin signal transduction, and serum adipokine levels in an animal model of diet-induced obesity and diabetes mellitus (DIO) was evaluated. Swiss mice were initially divided into two groups fed with regular rodent chow or with chow containing 24 g% saturated fat (DIO). DIO mice became obese and overtly diabetic after 8 weeks. DIO mice were then divided into three groups: control, sham, and visceral (epididymal and perinephric) fat removal. All groups were submitted to evaluation of basal glucose and insulin levels and i.p. insulin tolerance test. Insulin signal transduction in muscle was evaluated by immunoprecipitation and immunoblot, and serum adipokine levels were determined by ELISA. DIO mice became diabetic (228 versus 115 mg/dl), hyperinsulinemic (7.59 versus 3.15 ng/ml) and insulin resistant (K(itt) 2.88 versus 4.97%/min) as compared with control. Visceral fat removal partially reverted all parameters (147 mg/dl glucose; 3.82 ng/ml insulin; and 4.20%/min K(itt)). In addition, visceral fat removal completely reversed the impairment of insulin signal transduction through insulin receptor, insulin receptor substrate (IRS)-1, IRS-2 and Akt in muscle. Finally, serum levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were significantly increased, while adiponectin levels were significantly reduced in DIO mice. After visceral fat removal the levels of adipokines returned to near control levels. The present study shows that removal of visceral fat improves insulin signal transduction and glucose homeostasis in an animal model of diet-induced obesity and diabetes mellitus and these metabolic and molecular outcomes are accompanied by the restoration of adipokine levels. PMID:17170226

  17. Obesity

    Science.gov (United States)

    Obesity means having too much body fat. It is different from being overweight, which means weighing too ... what's considered healthy for his or her height. Obesity occurs over time when you eat more calories ...

  18. A Comparative Study of Lung Host Defense in Murine Obesity Models. Insights into Neutrophil Function.

    Science.gov (United States)

    Ubags, Niki D J; Burg, Elianne; Antkowiak, Maryellen; Wallace, Aaron M; Dilli, Estee; Bement, Jenna; Wargo, Matthew J; Poynter, Matthew E; Wouters, Emiel F M; Suratt, Benjamin T

    2016-08-01

    We have shown that obesity-associated attenuation of murine acute lung injury is driven, in part, by blunted neutrophil chemotaxis, yet differences were noted between the two models of obesity studied. We hypothesized that obesity-associated impairment of multiple neutrophil functions contributes to increased risk for respiratory infection but that such impairments may vary between murine models of obesity. We examined the most commonly used murine obesity models (diet-induced obesity, db/db, CPE(fat/fat), and ob/ob) using a Klebsiella pneumoniae pneumonia model and LPS-induced pneumonitis. Marrow-derived neutrophils from uninjured lean and obese mice were examined for in vitro functional responses. All obesity models showed impaired clearance of K. pneumoniae, but in differing temporal patterns. Failure to contain infection in obese mice was seen in the db/db model at both 24 and 48 hours, yet this defect was only evident at 24 hours in CPE(fat/fat) and ob/ob models, and at 48 hours in diet-induced obesity. LPS-induced airspace neutrophilia was decreased in all models, and associated with blood neutropenia in the ob/ob model but with leukocytosis in the others. Obese mouse neutrophils from all models demonstrated impaired chemotaxis, whereas neutrophil granulocyte colony-stimulating factor-mediated survival, LPS-induced cytokine transcription, and mitogen-activated protein kinase and signal transducer and activator of transcription 3 activation in response to LPS and granulocyte colony-stimulating factor, respectively, were variably impaired across the four models. Obesity-associated impairment of host response to lung infection is characterized by defects in neutrophil recruitment and survival. However, critical differences exist between commonly used mouse models of obesity and may reflect variable penetrance of elements of the metabolic syndrome, as well as other factors. PMID:27128821

  19. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome.

    Science.gov (United States)

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L; Ward, Leigh C; Mouatt, Peter; Brown, Lindsay

    2015-09-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID:26378573

  20. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Maharshi Bhaswant

    2015-09-01

    Full Text Available Both black (B and green (G cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom.

  1. Partial Physiologic Differences between High-fat Diet Induced Obesity-prone and Obesity-resistant Rats%高脂饮食诱导下肥胖易感大鼠与肥胖抗性大鼠间部分生理学指标差异的研究

    Institute of Scientific and Technical Information of China (English)

    周旭华; 郭锡熔; 丁胜利; 陈荣华; 莫宝庆; 刘倩琦; 费莉

    2004-01-01

    Objective: To observe the differences of partial physiologic indexes including weight, food intake,Lee's index, the wet weight of fat pad, plasma lipids and the genetic expression of LPL mRNA in adipose tissue between obesity-prone rats (OP) and obesity-resistant rats (OR) on a high-fat diet. Methods: After 1 week of free access to a high-fat diet (HFD), 48 rats were separated on the basis of 1 week body weight percentage gained in OP (OP≥P75)or OR ( OR≤ P25) groups. Rats were continuously fed on the HFD for another 4 weeks. The body weight and food intake were recorded in the course of model-making. And the Lee's index, the plasma lipid and lipoproteius, the wet weight of both epididymal and retroperitoneal fat pad were measured after the rat was killed. And the level of LPL mRNA exgain, the cumulative energy intake, the Lee' s index, and the wet weight of fat pad at both epididymal and retroperitoneal sites were significantly higher than those in OR rats, but there was no significant difference in the level of plasma weight in OP rats were about 6.45 and 4.25 times of those in OR rats. Meanwhile, the cumulative energy intake in OP level of LPL mRNA expression in adipose tissue, there was a significant level of LPL mRNA in adipose tissue of OP rats compared with that in OR rats. Conclusion: The physiologic differences exist between OP and OR rats. Besides a higher level of energy intake, the higher energy efficiency associated with LPL mRNA expression in adipose tissue may also contribute to the enhancement of susceptibility to obesity in OP rats.%目的:探讨高脂饮食诱导下肥胖易感(OP)大鼠肥胖抗性(OR)大鼠在体重、食量、Lee's指数、脂肪湿重、血脂及脂肪组织脂蛋白脂酶(LPL)基因表达等方面的生理学差异.方法:48只SD大鼠,以高脂饲料饲养1周后,按体重增值从大到小百分排序,取第75百分位以上为OP组,第25百分位以下为OR组,继续高脂饲养4周;观察各大鼠体重变化、摄食

  2. Lessons from Mouse Models of High-Fat Diet-Induced NAFLD

    Directory of Open Access Journals (Sweden)

    Yasuo Terauchi

    2013-10-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD encompasses a clinicopathologic spectrum of diseases ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH, the more aggressive form of fatty liver disease that may progress to cirrhosis and cirrhosis-related complications, including hepatocellular carcinoma. The prevalence of NAFLD, including NASH, is also increasing in parallel with the growing epidemics of obesity and diabetes. However, the causal relationships between obesity and/or diabetes and NASH or liver tumorigenesis have not yet been clearly elucidated. Animal models of NAFLD/NASH provide crucial information, not only for elucidating the pathogenesis of NAFLD/NASH, but also for examining therapeutic effects of various agents. A high-fat diet is widely used to produce hepatic steatosis and NASH in experimental animals. Several studies, including our own, have shown that long-term high-fat diet loading, which can induce obesity and insulin resistance, can also induce NASH and liver tumorigenesis in C57BL/6J mice. In this article, we discuss the pathophysiology of and treatment strategies for NAFLD and subsequent NAFLD-related complications such as NASH and liver tumorigenesis, mainly based on lessons learned from mouse models of high-fat diet-induced NAFLD/NASH.

  3. Apelin administration ameliorates high fat diet-induced cardiac hypertrophy and contractile dysfunction.

    Science.gov (United States)

    Ceylan-Isik, Asli F; Kandadi, Machender R; Xu, Xihui; Hua, Yinan; Chicco, Adam J; Ren, Jun; Nair, Sreejayan

    2013-10-01

    Apelin has been recognized as an adipokine that plays an important role in regulating energy metabolism and is credited with antiobesity and antidiabetic properties. This study was designed to examine the effect of exogenous apelin on obesity-associated cardiac dysfunction. Oral glucose tolerance test, echocardiography, cardiomyocyte contractile and intracellular Ca(2+) properties were assessed in adult C57BL/6J mice fed - low or a - high-fat diet for 24weeks followed by apelin treatment (100nmol/kg, i.p. for 2weeks). High-fat diet resulted in increased left ventricular diastolic and systolic diameters, and wall thickness, compromised fractional shortening, impaired cardiomyocyte mechanics (peak-shortening, maximal velocity of shortening/relengthening, and duration of shortening and relengthening) and compromised intracellular Ca(2+) handling, all of which were reconciled by apelin. Apelin treatment also reversed high fat diet-induced changes in intracellular Ca(2+) regulatory proteins, ER stress, and autophagy. In addition, microRNAs (miR) -133a, miR-208 and miR-1 which were elevated following high-fat feeding were attenuated by apelin treatment. In cultured cardiomyocytes apelin reconciled palmitic acid-induced cardiomyocyte contractile anomalies. Collectively, these data depict a pivotal role of apelin in obesity-associated cardiac contractile dysfunction, suggesting a therapeutic potential of apelin in the management of cardiac dysfunction associated with obesity. PMID:23859766

  4. Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4 deficient mice

    OpenAIRE

    Yewei Ji; Shengyi Sun; Julia K. Goodrich; Hana Kim; Angela C. Poole; Gerald E. Duhamel; Ruth E. Ley; Ling Qi

    2014-01-01

    Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here we show that chronic intake of a high-fat diet (HFD), not a low-fat diet (LFD), leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors (TLR) 2 and 4 (DKO hereafter). Diet-induced pulmonary lesions are blocked by antibiotics treatment and transmissible to wildtype mice upon either cohousing or fecal transplantation, pointin...

  5. Role of resistin in diet-induced hepatic insulin resistance

    OpenAIRE

    Muse, Evan D.; Obici, Silvana; Bhanot, Sanjay; Monia, Brett P.; McKay, Robert A.; Rajala, Michael W.; Scherer, Philipp E.; Rossetti, Luciano

    2004-01-01

    Resistin is an adipose-derived hormone postulated to link adiposity to insulin resistance. To determine whether resistin plays a causative role in the development of diet-induced insulin resistance, we lowered circulating resistin levels in mice by use of a specific antisense oligodeoxynucleotide (ASO) directed against resistin mRNA and assessed in vivo insulin action by the insulin-clamp technique. After 3 weeks on a high-fat (HF) diet, mice displayed severe insulin resistance associated wit...

  6. Obesity

    Science.gov (United States)

    ... obese, follow an unhealthy diet, and have an eating disorder all at the same time. Sometimes, medical problems or treatments cause weight gain, including: Underactive thyroid (hypothyroidism) Medicines such ...

  7. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer

    Science.gov (United States)

    Asgharpour, Amon; Cazanave, Sophie C.; Pacana, Tommy; Seneshaw, Mulugeta; Vincent, Robert; Banini, Bubu A.; Kumar, Divya Prasanna; Daita, Kalyani; Min, Hae-Ki; Mirshahi, Faridoddin; Bedossa, Pierre; Sun, Xiaochen; Hoshida, Yujin; Koduru, Srinivas V.; Contaifer, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S.; Sanyal, Arun J.

    2016-01-01

    Background & Aims The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development. Methods A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains. Results Following initiation of the obesogenic diet, B6/129 mice developed obesity, insulin resistance, hypertriglyceridemia and increased LDL-cholesterol. They sequentially also developed steatosis (4–8 weeks), steatohepatitis (16–24 weeks), progressive fibrosis (16 weeks onwards) and spontaneous hepatocellular cancer (HCC). There was a strong concordance between the pattern of pathway activation at a transcriptomic level between humans and mice with similar histological phenotypes (FDR 0.02 for early and 0.08 for late time points). Lipogenic, inflammatory and apoptotic signaling pathways activated in human NASH were also activated in these mice. The HCC gene signature resembled the S1 and S2 human subclasses of HCC (FDR 0.01 for both). Only the B6/129 mouse but not the parent strains recapitulated all of these aspects of human NAFLD. Conclusions We here describe a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND) that recapitulates the key physiological, metabolic, histologic, transcriptomic and cell-signaling changes seen in humans with progressive NASH. Lay summary We have developed a diet-induced mouse model of non-alcoholic steatohepatitis (NASH) and hepatic cancers in a cross between two mouse strains (129S1/SvImJ and C57Bl/6J). This model mimics all the physiological, metabolic, histological, transcriptomic gene signature and clinical endpoints of human NASH and can facilitate preclinical development of therapeutic targets for NASH. PMID:27261415

  8. Treadmill Intervention Attenuates the Cafeteria Diet-Induced Impairment of Stress-Coping Strategies in Young Adult Female Rats

    Science.gov (United States)

    Cigarroa, Igor; Lalanza, Jaume F.; Caimari, Antoni; del Bas, Josep M.; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M.

    2016-01-01

    The current prevalence of diet-induced overweight and obesity in adolescents and adults is continuously growing. Although the detrimental biochemical and metabolic consequences of obesity are widely studied, its impact on stress-coping behavior and its interaction with specific exercise doses (in terms of intensity, duration and frequency) need further investigation. To this aim, we fed adolescent rats either an obesogenic diet (cafeteria diet, CAF) or standard chow (ST). Each group was subdivided into four subgroups according to the type of treadmill intervention as follows: a sedentary group receiving no manipulation; a control group exposed to a stationary treadmill; a low-intensity treadmill group trained at 12 m/min; and a higher intensity treadmill group trained at 17 m/min. Both the diet and treadmill interventions started at weaning and lasted for 8 weeks. Subjects were tested for anxiety-like behavior in the open field test and for coping strategies in the two-way active avoidance paradigm at week 7 and were sacrificed at week 8 for biometric and metabolic characterization. CAF feeding increased the weight gain, relative retroperitoneal white adipose tissue (RWAT %), and plasma levels of glucose, insulin, triglycerides and leptin and decreased the insulin sensitivity. Treadmill intervention partially reversed the RWAT% and triglyceride alterations; at higher intensity, it decreased the leptin levels of CAF-fed animals. CAF feeding decreased the motor activity and impaired the performance in a two-way active avoidance assessment. Treadmill intervention reduced defecation in the shuttle box, suggesting diminished anxiety. CAF feeding combined with treadmill training at 17 m/min increased the time spent in the center of the open field and more importantly, partially reversed the two-way active avoidance deficit. In conclusion, this study demonstrates that at doses that decreased anxiety-like behavior, treadmill exercise partially improved the coping strategy

  9. Obesity

    DEFF Research Database (Denmark)

    Morgen, Camilla Schmidt; Sørensen, Thorkild I A

    2014-01-01

    A new report provides compelling evidence of the high prevalence of overweight and obesity throughout the world. The prevalence has increased since 1980, but at different rates across ages, times and locations. Studies exploring the causes of these differences could aid development of effective...

  10. MRI characterization of brown adipose tissue in obese and normal-weight children

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Zhang, Huiyuan [John H. Stroger, Jr. Hospital of Cook County, Collaborative Research Unit, Chicago, IL (United States); Kwon, Soyang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Stanley Manne Children' s Research Institute, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Josefson, Jami L. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Endocrinology, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States)

    2015-10-15

    Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

  11. MRI characterization of brown adipose tissue in obese and normal-weight children

    International Nuclear Information System (INIS)

    Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

  12. Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance

    Science.gov (United States)

    Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben

    2015-01-01

    Objective Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Methods Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. Results The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca2+-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. Conclusions This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia. PMID:26909312

  13. Western-style diet induces insulin insensitivity and hyperactivity in adolescent male rats.

    Science.gov (United States)

    Marwitz, Shannon E; Woodie, Lauren N; Blythe, Sarah N

    2015-11-01

    The prevalence of obesity in children and adolescents has increased rapidly over the past 30 years, as has the incidence of attention deficit hyperactivity disorder (ADHD). In 2012, it was found that overweight children have a twofold higher chance of developing ADHD than their normal weight counterparts. Previous work has documented learning and memory impairments linked to consumption of an energy-dense diet in rats, but the relationship between diet and ADHD-like behaviors has yet to be explored using animal models. Therefore, the purpose of this study was to explore the role of diet in the etiology of attention and hyperactivity disorders using a rat model of diet-induced obesity. Male Sprague-Dawley rats were fed either a control diet or a Western-style diet (WSD) for ten weeks, and specific physiological and behavioral effects were examined. Tail blood samples were collected to measure fasting blood glucose and insulin levels in order to assess insulin insensitivity. Rats also performed several behavioral tasks, including the open field task, novel object recognition test, and attentional set-shifting task. Rats exposed to a WSD had significantly higher fasting insulin levels than controls, but both groups had similar glucose levels. The quantitative insulin sensitivity check index (QUICKI) indicated the development of insulin resistance in WSD rats. Performance in the open field test indicated that WSD induced pronounced hyperactivity and impulsivity. Further, control diet animals were able to discriminate between old and novel objects, but the WSD animals were significantly impaired in object recognition. However, regardless of dietary condition, rats were able to perform the attentional set-shifting paradigm. While WSD impaired episodic memory and induced hyperactivity, attentional set-shifting capabilities are unaffected. With the increasing prevalence of both obesity and ADHD, understanding the potential links between the two conditions is of clinical

  14. A Drosophila model of high sugar diet-induced cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Jianbo Na

    Full Text Available Diets high in carbohydrates have long been linked to progressive heart dysfunction, yet the mechanisms by which chronic high sugar leads to heart failure remain poorly understood. Here we combine diet, genetics, and physiology to establish an adult Drosophila melanogaster model of chronic high sugar-induced heart disease. We demonstrate deterioration of heart function accompanied by fibrosis-like collagen accumulation, insulin signaling defects, and fat accumulation. The result was a shorter life span that was more severe in the presence of reduced insulin and P38 signaling. We provide evidence of a role for hexosamine flux, a metabolic pathway accessed by glucose. Increased hexosamine flux led to heart function defects and structural damage; conversely, cardiac-specific reduction of pathway activity prevented sugar-induced heart dysfunction. Our data establish Drosophila as a useful system for exploring specific aspects of diet-induced heart dysfunction and emphasize enzymes within the hexosamine biosynthetic pathway as candidate therapeutic targets.

  15. Ganglioside GM3 synthase depletion reverses neuropathic pain and small fiber neuropathy in diet-induced diabetic mice

    Science.gov (United States)

    Jayaraj, Nirupa D; Wilson, Heather M; Ren, Dongjun; Flood, Kelsey; Wang, Xiao-Qi; Shum, Andrew; Miller, Richard J; Paller, Amy S

    2016-01-01

    Background Small fiber neuropathy is a well-recognized complication of type 2 diabetes and has been shown to be responsible for both neuropathic pain and impaired wound healing. In previous studies, we have demonstrated that ganglioside GM3 depletion by knockdown of GM3 synthase fully reverses impaired wound healing in diabetic mice. However, the role of GM3 in neuropathic pain and small fiber neuropathy in diabetes is unknown. Purpose Determine whether GM3 depletion is able to reverse neuropathic pain and small fibers neuropathy and the mechanism of the reversal. Results We demonstrate that GM3 synthase knockout and the resultant GM3 depletion rescues the denervation in mouse footpad skin and fully reverses the neuropathic pain in diet-induced obese diabetic mice. In cultured dorsal root ganglia from diet-induced diabetic mice, GM3 depletion protects against increased intracellular calcium influx in vitro. Conclusions These studies establish ganglioside GM3 as a new candidate responsible for neuropathic pain and small fiber neuropathy in diabetes. Moreover, these observations indicate that systemic or topically applied interventions aimed at depleting GM3 may improve both the painful neuropathy and the wound healing impairment in diabetes by protecting against nerve end terminal degeneration, providing a disease-modifying approach to this common, currently intractable medical issue. PMID:27590073

  16. Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

    Directory of Open Access Journals (Sweden)

    Deanna L. Gibson

    2012-08-01

    Full Text Available The gastrointestinal (GI microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.

  17. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

    Directory of Open Access Journals (Sweden)

    Carl-Johan Boraxbekk

    2015-07-01

    Full Text Available Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010 after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA. Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

  18. Vascular Smooth Muscle Sirtuin-1 Protects Against Diet-Induced Aortic Stiffness.

    Science.gov (United States)

    Fry, Jessica L; Al Sayah, Leona; Weisbrod, Robert M; Van Roy, Isabelle; Weng, Xiang; Cohen, Richard A; Bachschmid, Markus M; Seta, Francesca

    2016-09-01

    Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed a high-fat, high-sucrose (HFHS) diet, serving as a model of human metabolic syndrome, and it is associated with activation of proinflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD(+)-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity, in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO). Similarly, VSM-specific genetic SirT1 overexpression (SMTG) prevented pulse wave velocity increases induced by HFHS feeding, during 8 months. Administration of resveratrol or S17834, 2 polyphenolic compounds known to activate SirT1, prevented HFHS-induced arterial stiffness and were mimicked by global SirT1 overexpression (SirT1 bacterial artificial chromosome overexpressor), without evident metabolic improvements. In addition, HFHS-induced pulse wave velocity increases were reversed by 1-week treatment with a specific, small molecule SirT1 activator (SRT1720). These beneficial effects of pharmacological or genetic SirT1 activation, against HFHS-induced arterial stiffness, were associated with a decrease in nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and vascular cell adhesion molecule (VCAM-1) and p47phox protein expressions, in aorta and VSM cells. In conclusion, VSM SirT1 activation decreases arterial stiffness in the setting of obesity by stimulating anti-inflammatory and antioxidant pathways in the aorta. SirT1 activators may represent a novel therapeutic approach to prevent arterial stiffness and associated cardiovascular complications in overweight/obese individuals with metabolic syndrome. PMID:27432859

  19. The effect of aspirin on atherogenic diet-induced diabetes mellitus.

    Science.gov (United States)

    Sethi, Apoorva; Parmar, Hamendra S; Kumar, Anil

    2011-06-01

    Exploration of atherogenic diet-induced diabetes mellitus and the evaluation of antidiabetic potential of aspirin were carried out in this study. Male albino Wistar rats were divided into three groups of seven each (1, 2 and 3). Animals of groups 2 and 3 received CCT diet (normal rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5%, 2-thiouracil), whereas the animals of group 1 received normal feed and served as control. In addition to CCT, animals of group 3 (CCT + Asp) also received aspirin (8 gm/kg), commencing from day 8 till the end of study (day 15). In another experiment (exp. 2), aspirin-supplemented normal rat chow (Asp) was fed to the animals for 7 days and compared with the normal rat chow-fed control group. In experiment 3, an in vitro nitric oxide radical-scavenging potential of aspirin at three different doses (25, 50 and 100 μg/ml) was evaluated. In response to CCT diet, a decrease in serum insulin, α-amylase activity, hepatic glycogen, pancreatic calcium with a concomitant increase in serum glucose, lipid profile (except high-density lipoprotein cholesterol (HDL-C)), pancreatic nitrite and lipid peroxidation and the size of adipocytes along with macrophages infiltration were observed. Aspirin administration to CCT diet-fed animals (CCT + Asp) reverted all the studied biochemical and histological changes towards normality. In experiment 2, aspirin administration decreased the serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and VLDL-C with concomitantly increased HDL-C and insulin; however, it increased hepatic glycogen and pancreatic calcium concentration with a decrease in pancreatic and adipose lipid peroxidation. In vitro assay revealed the nitric oxide radical-scavenging potential of aspirin in all the studied doses. It is concluded that CCT diet-induced diabetes mellitus might be the outcome of nitric oxide radical-induced oxidative stress in pancreatic tissue, as well as diminished

  20. Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Laura J Dixon

    Full Text Available Nonalcoholic steatohepatitis (NASH is associated with caspase activation. However, a role for pro-inflammatory caspases or inflammasomes has not been explored in diet-induced liver injury. Our aims were to examine the role of caspase-1 in high fat-induced NASH. C57BL/6 wild-type and caspase 1-knockout (Casp1(-/- mice were placed on a 12-week high fat diet. Wild-type mice on the high fat diet increased hepatic expression of pro-caspase-1 and IL-1β. Both wild-type and Casp1(-/- mice on the high fat diet gained more weight than mice on a control diet. Hepatic steatosis and TG levels were increased in wild-type mice on high fat diet, but were attenuated in the absence of caspase-1. Plasma cholesterol and free fatty acids were elevated in wild-type, but not Casp1(-/- mice, on high fat diet. ALT levels were elevated in both wild-type and Casp1(-/- mice on high fat diet compared to control. Hepatic mRNA expression for genes associated with lipogenesis was lower in Casp1(-/- mice on high fat diet compared to wild-type mice on high fat diet, while genes associated with fatty acid oxidation were not affected by diet or genotype. Hepatic Tnfα and Mcp-1 mRNA expression was increased in wild-type mice on high fat diet, but not in Casp1(-/- mice on high fat diet. αSMA positive cells, Sirius red staining, and Col1α1 mRNA were increased in wild-type mice on high fat diet compared to control. Deficiency of caspase-1 prevented those increases. In summary, the absence of caspase-1 ameliorates the injurious effects of high fat diet-induced obesity on the liver. Specifically, mice deficient in caspase-1 are protected from high fat-induced hepatic steatosis, inflammation and early fibrogenesis. These data point to the inflammasome as an important therapeutic target for NASH.

  1. Efeitos do exercício crônico sobre a concentração circulante da leptina e grelina em ratos com obesidade induzida por dieta Effects of the chronic exercise on the circulating concentration of leptin and ghrelin in rats With diet-induced obesity

    Directory of Open Access Journals (Sweden)

    Ricardo Eguchi

    2008-06-01

    Full Text Available A obesidade vem se tornando uma das maiores epidemias mundiais, dessa forma, conhecer sua etiologia e mecanismos que regulam seu desenvolvimento é de grande relevância para o seu Tratamento. Portanto, o objetivo do presente estudo foi avaliar os efeitos da obesidade exógena induzida pela dieta de cafeteria e da atividade física crônica em ratos, sobre a adiposidade e a concentração sérica dos hormônios reguladores do balanço energético (leptina e grelina. Foram utilizados 32 ratos Wistar machos, divididos em quatro grupos: Sedentário alimentado com dieta padrão (SN, sedentário alimentado com dieta de cafeteria (SC, treinado alimentado com dieta padrão (TN e treinado alimentado com dieta de cafeteria (TC. A dieta de cafeteria aumentou significativamente a adiposidade central (RET e visceral (EPI (pObesity is becoming one of the biggest worldwide epidemics. Therefore, knowing its etiology and mechanisms that regulate its development is of great relevance for its treatment. Thus, the aim of the present study was to evaluate the effects of obesity induced by the palatable hyperlipidic diet and of the chronic physical activity in rats, on the adiposity and the serum concentration of regulating hormones of the energy balance (leptin and ghrelin. 32 male Wistar rats were divided in four groups: Sedentary fed with chow diet (SN, sedentary fed with cafeteria diet (SC, trained fed with chow diet (TN and trained fed with cafeteria diet (TC. The cafeteria diet led to a significant increase of central (RET and visceral (EPI adiposity (p<0.05. Conversely,the exercise training minimized the effect of the cafeteria diet, diminishing the central and visceral adiposity. Leptin was also increased in the groups fed with the cafeteria diet, suggesting increase of the resistance to the action of this hormone. Chronic physical activity did not hinder the development of hyperleptinemia. Reduction in the serum ghrelin concentration was observed only in

  2. Diet-Induced Alterations in Gut Microflora Contribute to Lethal Pulmonary Damage in TLR2/TLR4-Deficient Mice

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    Yewei Ji

    2014-07-01

    Full Text Available Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here, we show that chronic intake of a high-fat diet (HFD, not a low-fat diet, leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors 2 and 4 (DKO. Diet-induced pulmonary lesions are blocked by antibiotic treatment and are transmissible to wild-type mice upon either cohousing or fecal transplantation, pointing to the existence of bacterial pathogens. Indeed, diet and innate deficiency exert significant impact on gut microbiota composition. Thus, chronic intake of HFD promotes severe pulmonary damage and mortality in DKO mice in part via gut dysbiosis, a finding that may be important for immunodeficient patients, particularly those on chemotherapy or radiotherapy, where gut-microbiota-caused conditions are often life threatening.

  3. Cafeteria diet induce changes in blood flow that are more related with heat dissipation than energy accretion

    Science.gov (United States)

    Sabater, David; Agnelli, Silvia; Arriarán, Sofía; Romero, María del Mar; Fernández-López, José Antonio; Alemany, Marià

    2016-01-01

    Background. A “cafeteria” diet is a self-selected high-fat diet, providing an excess of energy, which can induce obesity. Excess of lipids in the diet hampers glucose utilization eliciting insulin resistance, which, further limits amino acid oxidation for energy. Methods. Male Wistar rats were exposed for a month to “cafeteria” diet. Rats were cannulated and fluorescent microspheres were used to determine blood flow. Results. Exposure to the cafeteria diet did not change cardiac output, but there was a marked shift in organ irrigation. Skin blood flow decreased to compensate increases in lungs and heart. Blood flow through adipose tissue tended to increase in relation to controls, but was considerably increased in brown adipose tissue (on a weight basis). Discussion. The results suggest that the cafeteria diet-induced changes were related to heat transfer and disposal. PMID:27547590

  4. 过氧化物酶体增殖物激活受体γ激动剂对肥胖小鼠非肾上腺素能原代棕色脂肪功能和分化的影响%Effect of peroxisome hyperplasia activated receptor γ agonists on the differentiation and function of nonadrenergic primary brown adipose tissue cells in mice with diet-induced obesity

    Institute of Scientific and Technical Information of China (English)

    胡苏荣; 胡淼

    2013-01-01

    Objective To investigate the effect of peroxisome hyperplasia activated receptor γ (PPAR-γ) agonist(PGZ) on the differentiation and function of nonadrenergic primary brown adipose tissue cells in mice with high fat diet-induced obesity,and try to provide new treatment for obesity and type 2 diabetes.Methods Primary BAT cells were separated from high fat diet-induced C57BL/6J obesity(HFD) mice and cultured in DMEM culture medium.The primary BAT cells were divided into 10 culture dishes equally,and assigned as PGZ treatment group,and control group(treated with normal saline),5 dishes each group.The effects of PGZ on BAT cells were assessed by quantitative real-time polymerase chain reaction (RT-PCR),Gene of BAT:uncoupling protein-1 (UCP-1); elongase of very long chain fatty acids (ELOVL3) ; PPAR-γ co-activator-1 α (PGC1-α) ; PPAR-γ co-activator-1 β (PGC1-β) ; PRD1-BF-1-RIZ1 homologous domain containing protein-16 (PRDM16) ; CCAAT/enhancer binding protein β (CEBP/β) ; adiponectin:adipocyte fatty acid-binding protein2 (AP2) ; cytochrome c oxidase1 (CYC1) ; mitochondrial transcription factor A(TFAM).Western blotting was used to assess the expression of UCP-1 protein; and Oil red O staining was applied to measure the adipogenesis function of BAT.The t test is used between two groups,ANOVA and LSD test is used between multiple groups.Results The expression of mRNA associated with BAT chararcteristic genes (UCP-1、ELOVL3、PGC1-α、PGC1-β),lipogeneic genes (AP2),mitochondrial genes(CYC1 、TFAM),and differential genes(PRDM16、CEBP/β) increased in PGZ treated group when compared with those in control group,the relative expression of the genes in the two groups were listed as following:UCP-1:1100.0 ± 612.0,2.0 ± 0.4 ; ELOVL3:1461.0 ± 617.0,2.0 ± 1.2 ; PGC1-α:8.1 ±2.8,2.0±1.1;PGC1-β:8.3 ±2.8,2.0 ± 1.3;adiponectin:2.6 ±0.8,1.0 ±0.7;AP2:5.1 ±2.2,1.00 ±0.24;CYC1:3.1 ±0.8,1.0 ±0.4;TFAM:1.2 ±0.4,1.00 ±0.25 ;PRDM16:4.8 ± 2.6,2.0 ±0.3;CEBP/β:6

  5. Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue.

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    Hoffmann, Linda S; Etzrodt, Jennifer; Willkomm, Lena; Sanyal, Abhishek; Scheja, Ludger; Fischer, Alexander W C; Stasch, Johannes-Peter; Bloch, Wilhelm; Friebe, Andreas; Heeren, Joerg; Pfeifer, Alexander

    2015-01-01

    Obesity is characterized by a positive energy balance and expansion of white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) combusts energy to produce heat. Here we show that a small molecule stimulator (BAY 41-8543) of soluble guanylyl cyclase (sGC), which produces the second messenger cyclic GMP (cGMP), protects against diet-induced weight gain, induces weight loss in established obesity, and also improves the diabetic phenotype. Mechanistically, the haeme-dependent sGC stimulator BAY 41-8543 enhances lipid uptake into BAT and increases whole-body energy expenditure, whereas ablation of the haeme-containing β1-subunit of sGC severely impairs BAT function. Notably, the sGC stimulator enhances differentiation of human brown adipocytes as well as induces 'browning' of primary white adipocytes. Taken together, our data suggest that sGC is a potential pharmacological target for the treatment of obesity and its comorbidities. PMID:26011238

  6. Bardoxolone methyl prevents obesity and hypothalamic dysfunction.

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    Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Wang, Hongqin; Dinh, Chi H L; Huang, Xu-Feng

    2016-08-25

    High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet. Oral administration of BM via drinking water (10 mg/kg daily) for 21 weeks significantly prevented an increase in body weight, energy intake, hyperleptinemia, and peripheral fat accumulation in mice fed a HF diet. Furthermore, BM treatment prevented HF diet-induced decreases in the anorexigenic effects of peripheral leptin administration. In the mediobasal and paraventricular nuclei regions of the hypothalamus, BM administration prevented HF diet-induced impairments of the downstream protein kinase b (Akt) pathway of hypothalamic leptin signalling. BM treatment also prevented an increase in inflammatory cytokines, tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in these two hypothalamic regions. These results identify a potential novel neuropharmacological application for BM in preventing HF diet-induced obesity, hypothalamic leptin resistance, and inflammation. PMID:27417254

  7. Effect of Ginseng (Panax ginseng Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement

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    Chang Hyeon Park

    2015-01-01

    Full Text Available High-fat diet-induced obesity leads to type 2 diabetes. Recently, there has been growing apprehension about diabetes-associated cognitive impairment (DACM. The effect of ginseng (Panax ginseng berry ethyl acetate fraction (GBEF on mice with high-fat diet-induced cognitive impairment was investigated to confirm its physiological function. C57BL/6 mice were fed a high-fat diet for 5 weeks and then a high-fat diet with GBEF (20 and 50 mg/kg of body weight for 4 weeks. After three in vivo behavioral tests (Y-maze, passive avoidance, and Morris water maze tests, blood samples were collected from the postcaval vein for biochemical analysis, and whole brains were prepared for an ex vivo test. A method based on ultra-performance liquid chromatography (UPLC accurate-mass quadrupole time-of-flight mass spectrometry (Q-TOF/MS was used to determine major ginsenosides. GBEF decreased the fasting blood glucose levels of high-fat diet-induced diabetes mellitus (DM mice and improved hyperglycemia. Cognitive behavior tests were examined after setting up the DM mice. The in vivo experiments showed that mice treated with GBEF exhibited more improved cognitive behavior than DM mice. In addition, GBEF effectively inhibited the acetylcholinesterase (AChE activity and malondialdehyde (MDA levels of DM mice brain tissues. Q-TOF UPLC/MS analyses of GBEF showed that ginsenoside Re was the major ginsenoside.

  8. Effect of Ginseng (Panax ginseng) Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement.

    Science.gov (United States)

    Park, Chang Hyeon; Park, Seon Kyeong; Seung, Tae Wan; Jin, Dong Eun; Guo, Tianjiao; Heo, Ho Jin

    2015-01-01

    High-fat diet-induced obesity leads to type 2 diabetes. Recently, there has been growing apprehension about diabetes-associated cognitive impairment (DACM). The effect of ginseng (Panax ginseng) berry ethyl acetate fraction (GBEF) on mice with high-fat diet-induced cognitive impairment was investigated to confirm its physiological function. C57BL/6 mice were fed a high-fat diet for 5 weeks and then a high-fat diet with GBEF (20 and 50 mg/kg of body weight) for 4 weeks. After three in vivo behavioral tests (Y-maze, passive avoidance, and Morris water maze tests), blood samples were collected from the postcaval vein for biochemical analysis, and whole brains were prepared for an ex vivo test. A method based on ultra-performance liquid chromatography (UPLC) accurate-mass quadrupole time-of-flight mass spectrometry (Q-TOF/MS) was used to determine major ginsenosides. GBEF decreased the fasting blood glucose levels of high-fat diet-induced diabetes mellitus (DM) mice and improved hyperglycemia. Cognitive behavior tests were examined after setting up the DM mice. The in vivo experiments showed that mice treated with GBEF exhibited more improved cognitive behavior than DM mice. In addition, GBEF effectively inhibited the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) levels of DM mice brain tissues. Q-TOF UPLC/MS analyses of GBEF showed that ginsenoside Re was the major ginsenoside. PMID:26161118

  9. Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

    Science.gov (United States)

    Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity. PMID:26846206

  10. Effects of pioglitazone on the expression of genes relative to differentiation and function of primary brown adipose tissue cells in mice with diet-induced obesity%吡格列酮对肥胖小鼠原代棕色脂肪细胞分化和功能基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    胡淼; 刘娟; 王龙; 丁国宪

    2011-01-01

    观察吡格列酮对肥胖小鼠原代棕色脂肪(brown adipose tissue,BAT)细胞分化和功能基因表达的影响,并为治疗肥胖相关疾病寻找新思路.结果显示吡格列酮通过增强特异基因表达、促进分化成脂、提高线粒体功能等方面增强BAT细胞功能(P<0.05);这可能是吡格列酮改善机体代谢的重要原因.%The effect of pioglitazone on the expression of genes relative to differentiation and function of primary brown adipose tissue cells was detected for the new treatment of obesity and type 2 diabetes.The results showed that pioglitazone promoted the differentiation and function of brown adipocytes( P<0.05 ).