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Sample records for high-fructose diet induces

  1. Preventive effect of grape seed extract against high-fructose diet-induced insulin resistance and oxidative stress in rats.

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    Suwannaphet, Wannaporn; Meeprom, Aramsri; Yibchok-Anun, Sirintorn; Adisakwattana, Sirichai

    2010-07-01

    The purpose of the present study was to investigate the preventive effect of grape seed extract (GSE) on insulin resistance and oxidative stress in rats fed a high-fructose diet. After 8 weeks of the experiment, the fasting plasma glucose, insulin concentrations, and the homeostasis model assessment of basal insulin resistance (HOMA-IR) of rats fed a high-fructose diet supplemented with 1% GSE were significantly lower than that of a high-fructose diet group. In the oral glucose tolerance test, rats fed a high-fructose diet supplemented with 1% GSE had a significantly reduced plasma glucose and insulin concentrations after 15 min of glucose loading, indicating that GSE improved glucose intolerance. In addition, fed rats fed a high-fructose diet supplemented with 1% GSE markedly increased activity of hepatic superoxide dismutase, catalase, and suppressed lipid peroxidation when compared to rats fed a high-fructose diet. However, rats fed a high-fructose diet supplemented with GSE were not found to have a significant change in the activity of hepatic glutathione peroxidase. In conclusion, intake of GSE may be a feasible therapeutic strategy for prevention of a high-fructose diet-induced insulin resistance and oxidative stress. 2010 Elsevier Ltd. All rights reserved.

  2. Role of AMPD2 in impaired glucose tolerance induced by high fructose diet

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    Athanasius Wrin Hudoyo

    2017-12-01

    Full Text Available A high intake of products containing fructose is known to mediate insulin resistance. In the liver, AMPD2, an isoform of AMPD, has important glucose metabolic homeostasis functions including maintenance of AMP-activated protein kinase (AMPK. We speculated that AMPD2 induces impaired glucose tolerance in individuals who consume a high-fructose diet. We gave either a normal-chow (NCD or high-fructose (HFrD diet for 40 days to 8-week-old male wild-type (WT and Ampd2−/− homozygote (A2−/− C57BL/6 mice. A glucose tolerance test (GTT and pyruvate tolerance test (PTT were used to evaluate glucose metabolism. In addition, gluconeogenesis and glycolysis enzymes, and AMPK phosphorylation in the liver were investigated. With consumption of the HFrD, A2−/− mice showed enhanced glucose tolerance in GTT and PTT results as compared to the WT mice, which were independent of changes in body weight. Also, the levels of phosphoenolpyruvate carboxy kinase and glucose-6-phosphatase (hepatic gluconeogenic enzymes were significantly reduced in A2−/− as compared to WT mice. The hepatic glycolytic enzymes glucokinase, phosphofructokinase, and pyruvate kinase were also examined, though there were no significant differences between genotypes in regard to both mRNA expression and protein expression under HFrD. Surprisingly, hepatic AMPK phosphorylation resulted in no changes in the A2−/− as compared to WT mice under these conditions. Our results indicated that Ampd2–deficient mice are protected from high fructose diet-induced glycemic dysregulation, mainly because of gluconeogenesis inhibition, and indicate a novel therapeutic target for type 2 diabetes mellitus.

  3. Maternal High Fructose Intake Increases the Vulnerability to Post-Weaning High-Fat Diet-Induced Programmed Hypertension in Male Offspring.

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    Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

    2018-01-09

    Widespread consumption of high-fructose and high-fat diets relates to the global epidemic of hypertension. Hypertension may originate from early life by a combination of prenatal and postnatal nutritional insults. We examined whether maternal high-fructose diet increases vulnerability to post-weaning high-fructose or high-fat diets induced hypertension in adult offspring and determined the underlying mechanisms. Pregnant Sprague-Dawley rats received regular chow (ND) or chow supplemented with 60% fructose (HFR) during the entire pregnancy and lactation periods. Male offspring were onto either the regular chow, 60% fructose, or high-fat diet (HFA) from weaning to 12 weeks of age and assigned to four groups: ND/ND, HFR/ND, HFR/HFR, and HFR/HFA. Maternal high-fructose diet exacerbates post-weaning high-fat diet-induced programmed hypertension. Post-weaning high-fructose and high-fat diets similarly reduced Sirt4, Prkaa2, Prkag2, Ppara, Pparb, and Ppargc1a mRNA expression in offspring kidneys exposed to maternal high-fructose intake. Additionally, post-weaning high-fat diet significantly reduced renal mRNA levels of Ulk1, Atg5, and Nrf2 and induced greater oxidative stress than did high-fructose diet. Although maternal high-fructose intake increases soluble epoxide hydrolase (SEH) expression in the kidney, which was restored by post-weaning high-fructose and high-fat diets. Maternal high-fructose diet programs differential vulnerability to developing hypertension in male offspring in response to post-weaning high-fructose and high-fat diets. Our data implicated that specific therapy targeting on nutrient sensing signals, oxidative stress, and SEH may be a promising approach to prevent hypertension in children and mothers exposed to high-fructose and high-fat consumption.

  4. Gastrodia elata Ameliorates High-Fructose Diet-Induced Lipid Metabolism and Endothelial Dysfunction

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    Min Chul Kho

    2014-01-01

    Full Text Available Overconsumption of fructose results in dyslipidemia, hypertension, and impaired glucose tolerance, which have documented correlation with metabolic syndrome. Gastrodia elata, a widely used traditional herbal medicine, was reported with anti-inflammatory and antidiabetes activities. Thus, this study examined whether ethanol extract of Gastrodia elata Blume (EGB attenuate lipid metabolism and endothelial dysfunction in a high-fructose (HF diet animal model. Rats were fed the 65% HF diet with/without EGB 100 mg/kg/day for 8 weeks. Treatment with EGB significantly suppressed the increments of epididymal fat weight, blood pressure, plasma triglyceride, total cholesterol levels, and oral glucose tolerance, respectively. In addition, EGB markedly prevented increase of adipocyte size and hepatic accumulation of triglycerides. EGB ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1 and adhesion molecules in the aorta. Moreover, EGB significantly recovered the impairment of vasorelaxation to acetylcholine and levels of endothelial nitric oxide synthase (eNOS expression and induced markedly upregulation of phosphorylation AMP-activated protein kinase (AMPKα in the liver, muscle, and fat. These results indicate that EGB ameliorates dyslipidemia, hypertension, and insulin resistance as well as impaired vascular endothelial function in HF diet rats. Taken together, EGB may be a beneficial therapeutic approach for metabolic syndrome.

  5. Blackcurrant Suppresses Metabolic Syndrome Induced by High-Fructose Diet in Rats

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    Ji Hun Park

    2015-01-01

    Full Text Available Increased fructose ingestion has been linked to obesity, hyperglycemia, dyslipidemia, and hypertension associated with metabolic syndrome. Blackcurrant (Ribes nigrum; BC is a horticultural crop in Europe. To induce metabolic syndrome, Sprague-Dawley rats were fed 60% high-fructose diet. Treatment with BC (100 or 300 mg/kg/day for 8 weeks significantly suppressed increased liver weight, epididymal fat weight, C-reactive protein (CRP, total bilirubin, leptin, and insulin in rats with induced metabolic syndrome. BC markedly prevented increased adipocyte size and hepatic triglyceride accumulation in rats with induced metabolic syndrome. BC suppressed oral glucose tolerance and protein expression of insulin receptor substrate-1 (IRS-1 and phosphorylated AMP-activated protein kinase (p-AMPK in muscle. BC significantly suppressed plasma total cholesterol, triglyceride, and LDL content. BC suppressed endothelial dysfunction by inducing downregulation of endothelin-1 and adhesion molecules in the aorta. Vascular relaxation of thoracic aortic rings by sodium nitroprusside and acetylcholine was improved by BC. The present study provides evidence of the potential protective effect of BC against metabolic syndrome by demonstrating improvements in dyslipidemia, hypertension, insulin resistance, and obesity in vivo.

  6. α-Amyrin attenuates high fructose diet-induced metabolic syndrome in rats.

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    Prabhakar, Pankaj; Reeta, K H; Maulik, Subir Kumar; Dinda, Amit Kumar; Gupta, Yogendra Kumar

    2017-01-01

    This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose-dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

  7. Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver.

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    Chukijrungroat, Natsasi; Khamphaya, Tanaporn; Weerachayaphorn, Jittima; Songserm, Thaweesak; Saengsirisuwan, Vitoon

    2017-08-01

    The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis. Copyright © 2017 the American Physiological Society.

  8. Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

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    El Mesallamy Hala O

    2010-06-01

    Full Text Available Abstract Background High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin. Methods Oral glucose tolerance tests (OGTT were carried out, homeostasis model assessment of insulin resistance (HOMA was calculated, homocysteine (Hcy, lipid concentrations and markers of oxidative stress were measured in male Wistar rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD, and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p. route for 35 days. Results Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy, lower total antioxidant capacity (TAC, lower paraoxonase (PON activity, and higher nitric oxide metabolites (NOx concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs by 22.5%, total cholesterol (T-Chol by 11%, and low density lipoprotein cholesterol (LDL-C by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration. Conclusion Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS, and that taurine has a protective role against

  9. A High-Fructose-High-Coconut Oil Diet Induces Dysregulating Expressions of Hippocampal Leptin and Stearoyl-CoA Desaturase, and Spatial Memory Deficits in Rats.

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    Lin, Ching-I; Shen, Chu-Fu; Hsu, Tsui-Han; Lin, Shyh-Hsiang

    2017-06-16

    We investigated the effects of high-fructose-high-fat diets with different fat compositions on metabolic parameters, hippocampal-dependent cognitive function, and brain leptin (as well as stearoyl-CoA desaturase (SCD1) mRNA expressions). Thirty-two male Wistar rats were divided into 3 groups, a control group ( n = 8), a high-fructose soybean oil group (37.5% of fat calories, n = 12), and a high-fructose coconut oil group (37.5% of fat calories, n = 12) for 20 weeks. By the end of the study, the coconut oil group exhibited significantly higher serum fasting glucose, fructosamine, insulin, leptin, and triglyceride levels compared to those of the control and soybean oil groups. However, hippocampal leptin expression and leptin receptor mRNA levels were significantly lower, while SCD1 mRNA was significantly higher in rats fed the high-fructose-high-coconut oil diet than in rats fed the other experimental diets. In addition, the coconut oil group spent significantly less time in the target quadrant on the probe test in the Morris water maze (MWM) task. Rats fed the high-fructose-high-coconut oil diet for 20 weeks were prone to develop hyperglycemia, hyperinsulinemia, hyperleptinemia, and hypertriglyceridemia. These metabolic consequences may contribute to hippocampal-dependent memory impairment, accompanied by a lower central leptin level, and a higher SCD1 gene expression in the brain.

  10. Beneficiary effect of Commiphora mukul ethanolic extract against high fructose diet induced abnormalities in carbohydrate and lipid metabolism in wistar rats

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    Ramesh Bellamkonda

    2018-01-01

    Full Text Available The present study was proposed to elucidate the effect of Commiphora mukul gum resin elthanolic extract treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats were divided into four groups: two of these groups (group C and C+CM were fed with standard pellet diet and the other two groups (group F and F+CM were fed with high fructose (66 % diet. C. mukul suspension in 5% Tween-80 in distilled water (200 mg/kg body weight/day was administered orally to group C+CM and group F+CM. At the end of 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. mukul treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F decreased significantly with C. mukul treatment in group F+CM. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. mukul treatment in group F+CM. In conclusion, our study demonstrated that C. mukul treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose induced alterations in carbohydrate and lipid metabolisms by the extract which was further supported by histopathological results from liver samples which showed regeneration of the hepatocytes. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

  11. Beneficiary effect ofCommiphora mukulethanolic extract against high fructose diet induced abnormalities in carbohydrate and lipid metabolism in wistar rats.

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    Bellamkonda, Ramesh; Karuna, Rasineni; Sasi Bhusana Rao, Bongu; Haritha, Ketham; Manjunatha, Bengeppagari; Silpa, Somavarapu; Saralakumari, Desireddy

    2018-01-01

    The present study was proposed to elucidate the effect of Commiphora mukul gum resin elthanolic extract treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats were divided into four groups: two of these groups (group C and C+CM) were fed with standard pellet diet and the other two groups (group F and F+CM) were fed with high fructose (66 %) diet. C. mukul suspension in 5% Tween-80 in distilled water (200 mg/kg body weight/day) was administered orally to group C+CM and group F+CM. At the end of 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. mukul treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F decreased significantly with C. mukul treatment in group F+CM. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. mukul treatment in group F+CM. In conclusion, our study demonstrated that C. mukul treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose induced alterations in carbohydrate and lipid metabolisms by the extract which was further supported by histopathological results from liver samples which showed regeneration of the hepatocytes. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

  12. Inhibitory effects of eucalyptus and banaba leaf extracts on nonalcoholic steatohepatitis induced by a high-fructose/high-glucose diet in rats.

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    Takahashi, Yoshihisa; Sugimoto, Keiichiro; Soejima, Yurie; Kumagai, Arisa; Koeda, Tatsuki; Shojo, Aiko; Nakagawa, Kazuya; Harada, Naoki; Yamaji, Ryoichi; Inui, Hiroshi; Yamanouchi, Toshikazu; Fukusato, Toshio

    2015-01-01

    Nonalcoholic steatohepatitis (NASH) is a liver disease associated with metabolic syndrome. The aim of this work was to examine whether eucalyptus (Eucalyptus globulus) leaf extract (ELE) and banaba (Lagerstroemia speciosa L.) leaf extract (BLE) inhibited NASH induced by excessive ingestion of fructose in rats. Wistar rats were divided into four groups according to four distinct diets: starch diet (ST), high-fructose/high-glucose diet (FG), FG diet supplemented with ELE, or FG diet supplemented with BLE. All rats were killed after 5 weeks of treatment. Serum alanine aminotransferase and total cholesterol levels were significantly lower in the BLE group than in the FG group. Liver histopathology, including steatosis, lipogranulomas, and perisinusoidal fibrosis, was significantly attenuated in the ELE and BLE groups compared with the FG group. Levels of 2-thiobarbituric acid reactive substances (TBARS), which reflect oxidative injury to the liver, were significantly suppressed by ELE and BLE. Western blotting analysis indicated that interleukin-6 expression levels were significantly lower in the ELE and BLE groups than in the FG group. These results suggest that ELE and BLE reduced lipogenesis, oxidative stress, and inflammatory cytokine expression and thus inhibited NASH induced by excessive ingestion of fructose in rats.

  13. Aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (Apocynaceae) palliates hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome in rats.

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    Ajiboye, T O; Hussaini, A A; Nafiu, B Y; Ibitoye, O B

    2017-02-23

    Hunteria umbellata is used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous seed extract of Hunteria umbellata on insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome MATERIALS AND METHODS: Rats were randomized into seven groups (A-G). Control (group A) and group C rats received control diet for nine weeks while rats in groups B, D - G were placed on high-fructose diet for 9 weeks. In addition to the diets, groups C - F rats orally received 400, 100, 200 and 400mg/kg body weight aqueous seed extract of Hunteria umbellata for 3 weeks starting from 6th - 9th week. High-fructose diet (when compared to control rats) mediated a significant (p<0.05) increase in body weight, body mass index and abdominal circumference. Similarly, levels of blood glucose, insulin, leptin, adiponectin and insulin resistance were increased. It also caused a significant increase in the levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index while high-density lipoprotein cholesterol was decreased significantly. Levels of proinflammatory factor, tumour necrosis factor-α, interleukin-6 and 8 were also increased by the high fructose diet. Moreover, it mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and level of glutathione reduced. Conversely, levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were elevated. Aqueous seed extract of Hunteria umbellata significantly ameliorated the high fructose diet-mediated alterations. From this study, it is concluded that aqueous seed extract of Hunteria umbellata possesses hypoglycemic, hypolipidemic and antioxidants abilities as evident from its capability to

  14. Ambient fine particulate matter and ozone exposures induce inflammation in epicardial and perirenal adipose tissues in rats fed a high fructose diet

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    2013-01-01

    Background Inflammation and oxidative stress play critical roles in the pathogenesis of inhaled air pollutant-mediated metabolic disease. Inflammation in the adipose tissues niches are widely believed to exert important effects on organ dysfunction. Recent data from both human and animal models suggest a role for inflammation and oxidative stress in epicardial adipose tissue (EAT) as a risk factor for the development of cardiovascular disease. We hypothesized that inhalational exposure to concentrated ambient fine particulates (CAPs) and ozone (O3) exaggerates inflammation and oxidative stress in EAT and perirenal adipose tissue (PAT). Methods Eight- week-old Male Sprague–Dawley rats were fed a normal diet (ND) or high fructose diet (HFr) for 8 weeks, and then exposed to ambient AIR, CAPs at a mean of 356 μg/m3, O3 at 0.485 ppm, or CAPs (441 μg/m3) + O3 (0.497 ppm) in Dearborn, MI, 8 hours/day, 5 days/week, for 9 days over 2 weeks. Results EAT and PAT showed whitish color in gross, and less mitochondria, higher mRNA expression of white adipose specific and lower brown adipose specific genes than in brown adipose tissues. Exposure to CAPs and O3 resulted in the increase of macrophage infiltration in both EAT and PAT of HFr groups. Proinflammatory genes of Tnf-α, Mcp-1 and leptin were significantly upregulated while IL-10 and adiponectin, known as antiinflammatory genes, were reduced after the exposures. CAPs and O3 exposures also induced an increase in inducible nitric oxide synthase (iNOS) protein expression, and decrease in mitochondrial area in EAT and PAT. We also found significant increases in macrophages of HFr-O3 rats. The synergetic interaction of HFr and dirty air exposure on the inflammation was found in most of the experiments. Surprisingly, exposure to CAPs or O3 induced more significant inflammation and oxidative stress than co-exposure of CAPs and O3 in EAT and PAT. Conclusion EAT and PAT are both white adipose tissues. Short

  15. A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

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    Kanokwan Jarukamjorn

    2016-01-01

    Full Text Available Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD, associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx, were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD.

  16. Effects of ferulic acid and γ-oryzanol on high-fat and high-fructose diet-induced metabolic syndrome in rats.

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    Ou Wang

    Full Text Available The high morbidity of metabolic dysfunction diseases has heightened interest in seeking natural and safe compounds to maintain optimal health. γ-Oryzanol (OZ, the ferulic acid (FA ester with phytosterols, mainly present in rice bran has been shown to improve markers of metabolic syndrome. This study investigates the effects of FA and OZ on alleviating high-fat and high-fructose diet (HFFD-induced metabolic syndrome parameters.Male SD rats were fed with a regular rodent diet, HFFD, or HFFD supplemented with 0.05% FA or 0.16% OZ (equimolar concentrations for 13 weeks. Food intake, organ indices, serum lipid profiles, glucose metabolism, insulin resistance (IR index and cytokine levels were analyzed. The mechanisms were further investigated in oleic acid-stimulated HepG2 cells by analyzing triglyceride (TG content and lipogenesis-related gene expressions.In the in vivo study, FA and OZ exhibited similar effects in alleviating HFFD-induced obesity, hyperlipidemia, hyperglycemia, and IR. However, only OZ treatment significantly decreased liver index and hepatic TG content, lowered serum levels of C-reactive protein and IL-6, and increased serum concentration of adiponectin. In the in vitro assay, only OZ administration significantly inhibited intracellular TG accumulation and down-regulated expression of stearoyl coenzyme-A desaturase-1, which might facilitate OZ to enhance its hepatoprotective effect.OZ is more effective than FA in inhibiting hepatic fat accumulation and inflammation. Thus, FA and OZ could be used as dietary supplements to alleviate the deleterious effects of HFFD.

  17. Selenium-containing polysaccharides from Ziyang green tea ameliorate high-fructose diet induced insulin resistance and hepatic oxidative stress in mice.

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    Ren, Daoyuan; Hu, Yuanyuan; Luo, Yiyang; Yang, Xingbin

    2015-10-01

    The present study was designed to evaluate the effects of selenium-containing tea polysaccharides (Se-GTP) from a new variety of selenium-enriched Ziyang green tea against high fructose (HF)-induced insulin resistance and hepatic oxidative stress in mice. Healthy male Kunming mice were fed 20% high fructose water and administered 200, 400 and 800 mg per kg bw Se-GTP for 8 weeks. Mice fed HF in drinking water displayed significant insulin resistance, hepatic steatosis and oxidative stress observed by hyperglycemia and hyperinsulinemia, as well as increases in hepatic non-esterified fatty acid (NEFA) and malonaldehyde (MDA). The administration of Se-GTP at 400 and 800 mg per kg bw significantly improved insulin sensitivity, and reduced liver steatosis and oxidative stress damage, and brought back the antioxidants and hepatic lipids towards near-normal values. In the oral glucose tolerance test, the administration of Se-GTP at 400 and 800 mg per kg bw had reduced plasma glucose concentrations after 30 min of glucose loading in HF-fed mice, suggesting that Se-GTP improved glucose intolerance. Histopathological examination indicated that the impaired pancreatic/hepatic tissues were effectively restored in HF-fed mice following the Se-GTP treatment. This is the first report showing that Se-GTP can ameliorate the high fructose-induced insulin resistance and hepatic oxidative injury.

  18. Effect of pomegranate extracts on brain antioxidant markers and cholinesterase activity in high fat-high fructose diet induced obesity in rat model.

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    Amri, Zahra; Ghorbel, Asma; Turki, Mouna; Akrout, Férièle Messadi; Ayadi, Fatma; Elfeki, Abdelfateh; Hammami, Mohamed

    2017-06-27

    To investigate beneficial effects of Pomegranate seeds oil (PSO), leaves (PL), juice (PJ) and (PP) on brain cholinesterase activity, brain oxidative stress and lipid profile in high-fat-high fructose diet (HFD) induced-obese rat. In vitro and in vivo cholinesterase activity, brain oxidative status, body and brain weight and plasma lipid profile were measured in control rats, HFD-fed rats and HFD-fed rats treated by PSO, PL, PJ and PP. In vitro study showed that PSO, PL, PP, PJ inhibited cholinesterase activity in dose dependant manner. PL extract displayed the highest inhibitory activity by IC50 of 151.85 mg/ml. For in vivo study, HFD regime induced a significant increase of cholinesterase activity in brain by 17.4% as compared to normal rats. However, the administration of PSO, PL, PJ and PP to HDF-rats decreased cholinesterase activity in brain respectively by 15.48%, 6.4%, 20% and 18.7% as compared to untreated HFD-rats. Moreover, HFD regime caused significant increase in brain stress, brain and body weight, and lipid profile disorders in blood. Furthermore, PSO, PL, PJ and PP modulated lipid profile in blood and prevented accumulation of lipid in brain and body evidenced by the decrease of their weights as compared to untreated HFD-rats. In addition administration of these extract protected brain from stress oxidant, evidenced by the decrease of malondialdehyde (MDA) and Protein carbonylation (PC) levels and the increase in superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. These findings highlight the neuroprotective effects of pomegranate extracts and one of mechanisms is the inhibition of cholinesterase and the stimulation of antioxidant capacity.

  19. Epigenomic derangement of hepatic glucose metabolism by feeding of high fructose diet and its prevention by Rosiglitazone in rats.

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    Yadav, H; Jain, S; Yadav, M; Sinha, P R; Prasad, G B K S; Marotta, F

    2009-07-01

    The high consumption of fructose leads to the increasing incidence of insulin resistance by several unknown mechanisms. Hepatic glucose metabolism may also be an important target of fructose-induced-metabolic alterations. The aim of present study was to investigate alterations in hepatic glycogenolysis, glycogenesis and gluconeogenic fluxes by feeding of 21% high fructose diet and the effects of Rosiglitazone treatment to prevent these derangements in rats. Rats were maintained on normal chow and high fructose diet with or without Rosiglitazone for 8 weeks and various biochemical and gene expression measures were estimated. The feeding of high fructose diet impaired glucose, insulin and pyruvate tolerance tests and increased blood HbA(1c), insulin, triglyceride, free fatty acids and homeostasis model assessment after 8 weeks. In addition, high fructose diet feeding increased expression of phosphoenol-pyruvatecorboxykinase, glucose-6-phosphatase, sterol regulatory element binding proteins-1 and fatty acid synthase through enhanced expression of fork-head receptor, peroxisome proliferator activated receptor-gamma-co-activator 1 and cAMP reactive element binding protein. The treatment with Rosiglitazone inhibited all these derangements, i.e. hepato-lipogenic and gluconeogenic effects of high fructose diet feeding in rats. Together these findings suggest that high fructose diet induced hepatic gluconeogenic and lipogenic rate, and increased circulating triglycerides and free fatty acids, which may be the major risk factors for glucose intolerance, hyperglycemia and insulin resistance in rats. In such situations high fructose flux also induces transcriptional cascade of gluconeogenic enzymes through the modulation of various associated transcriptional factors.

  20. Glucose transporter-8 (GLUT8) mediates glucose intolerance and dyslipidemia in high-fructose diet-fed male mice.

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    DeBosch, Brian J; Chen, Zhouji; Finck, Brian N; Chi, Maggie; Moley, Kelle H

    2013-11-01

    Members of the glucose transporter (GLUT) family of membrane-spanning hexose transporters are subjects of intensive investigation for their potential as modifiable targets to treat or prevent obesity, metabolic syndrome, and type 2 diabetes mellitus. Mounting evidence suggests that the ubiquitously expressed class III dual-specificity glucose and fructose transporter, GLUT8, has important metabolic homeostatic functions. We therefore tested the hypothesis that GLUT8 mediates the deleterious metabolic effects of chronic high-fructose diet exposure. Here we demonstrate resistance to high-fructose diet-induced glucose intolerance and dyslipidemia concomitant with enhanced oxygen consumption and thermogenesis in GLUT8-deficient male mice. Independent of diet, significantly lower systolic blood pressure both at baseline and after high-fructose diet feeding was also observed by tail-cuff plethysmography in GLUT8-deficient mice vs wild-type controls. Resistance to fructose-induced metabolic dysregulation occurred in the context of enhanced hepatic peroxisome proliferator antigen receptor-γ (PPARγ) protein abundance, whereas in vivo hepatic adenoviral GLUT8 overexpression suppressed hepatic PPARγ expression. Taken together, these findings suggest that GLUT8 blockade prevents fructose-induced metabolic dysregulation, potentially by enhancing hepatic fatty acid metabolism through PPARγ and its downstream targets. We thus establish GLUT8 as a promising target in the prevention of diet-induced obesity, metabolic syndrome, and type 2 diabetes mellitus in males.

  1. Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet.

    Science.gov (United States)

    Wada, Tsutomu; Kenmochi, Hiroki; Miyashita, Yusuke; Sasaki, Motohiro; Ojima, Minoru; Sasahara, Masakiyo; Koya, Daisuke; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2010-05-01

    Recent evidence suggests that treatment with mineralocorticoid receptor antagonist suppressed local inflammation in vascular tissues or cardiomyocytes; therefore, we examined the effect of spironolactone on glucose and lipid metabolism in a mouse model with diet-induced diabetes and nonalcoholic fatty liver disease. C57BL/6 mice were fed either the control diet, 60% fat diet with 30% fructose water (HFFD), or HFFD with spironolactone for 8 wk. HFFD mice demonstrated apparent phenotypes of metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and fatty liver. Although treatment with spironolactone did not affect the increased calorie intake and body weight by HFFD, the increments of epididymal fat weight, blood pressure, serum triglyceride, free fatty acids, leptin, and total cholesterol levels were significantly suppressed. Elevation of blood glucose during glucose and insulin tolerance tests in HFFD mice was significantly lowered by spironolactone. Notably, increased glucose levels during pyruvate tolerance test in HFFD mice were almost completely ameliorated to control levels by the treatment. Staining with hematoxylin-eosin (HE) and Oil-red-O demonstrated marked accumulation of triglycerides in the centrilobular part of the hepatic lobule in HFFD mice, and these accumulations were effectively improved by spironolactone. Concomitantly HFFD feeding markedly up-regulated hepatic mRNA expression of proinflammatory cytokines (TNFalpha, IL-6, and monocyte chemoattractant protein-1), gluconeogenic gene phosphoenolpyruvate carboxykinase, transcription factor carbohydrate response element binding protein, and its downstream lipogenic enzymes, all of which were significantly suppressed by spironolactone. These results indicate that inhibition of mineralocorticoid receptor might be a beneficial therapeutic approach for diet-induced phenotypes of metabolic syndrome and fatty liver.

  2. Long term metabolic syndrome induced by a high fat high fructose diet leads to minimal renal injury in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Romain Dissard

    Full Text Available Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD. C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat and drinking water enriched with fructose (30%. Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418 together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217 but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease.

  3. Individual CLA Isomers, c9t11 and t10c12, Prevent Excess Liver Glycogen Storage and Inhibit Lipogenic Genes Expression Induced by High-Fructose Diet in Rats

    Directory of Open Access Journals (Sweden)

    Edyta Maslak

    2015-01-01

    Full Text Available This study assessed the effects of individual conjugated linoleic acid isomers, c9t11-CLA and t10c12-CLA, on nonalcoholic fatty liver disease (NAFLD and systemic endothelial dysfunction in rats fed for four weeks with control or high-fructose diet. The high-fructose diet hampered body weight gain (without influencing food intake, increased liver weight and glycogen storage in hepatocytes, upregulated expression of fatty acid synthase (FAS and stearoyl-CoA desaturase-1 (SCD-1, and increased saturated fatty acid (SFA content in the liver. Both CLA isomers prevented excessive accumulation of glycogen in the liver. Specifically, t10c12-CLA decreased concentration of serum triacylglycerols and LDL + VLDL cholesterol, increased HDL cholesterol, and affected liver lipid content and fatty acid composition by downregulation of liver SCD-1 and FAS expression. In turn, the c9t11-CLA decreased LDL+VLDL cholesterol in the control group and downregulated liver expression of FAS without significant effects on liver weight, lipid content, and fatty acid composition. In summary, feeding rats with a high-fructose diet resulted in increased liver glycogen storage, indicating the induction of gluconeogenesis despite simultaneous upregulation of genes involved in de novo lipogenesis. Although both CLA isomers (c9t11 and t10c12 display hepatoprotective activity, the hypolipemic action of the t10c12-CLA isomer proved to be more pronounced than that of c9t11-CLA.

  4. Histologic and Metabolic Derangement in High-Fat, High-Fructose, and Combination Diet Animal Models

    Directory of Open Access Journals (Sweden)

    Jai Sun Lee

    2015-01-01

    Full Text Available Background. We used high-fat (HF, high-fructose (HFr, and combination diets to create a dietary animal model of nonalcoholic fatty liver disease (NAFLD. Comparison of both clinical phenotypes has not been well defined. The purpose of this study was to compare histologic and metabolic characteristics between diets in an animal model of NAFLD. Methods. NAFLD was induced in rats by feeding them HF, HFr, and combination (HF + HFr diets for 20 weeks. The degree of intrahepatic fat accumulation, inflammation, and oxidative stress was evaluated. Metabolic derangements were assessed by the oral glucose tolerance test and the intrahepatic insulin signal pathway. Results. Body weight gain and intrahepatic fat accumulation were more prominent in the HF feeding group than in the HFr group. The expressions of NOX-4 and TLR-4 were higher in the HF and HFr combination groups than in the HF-only group. Other intrahepatic inflammatory markers, MCP-1, TNF-α, and endoplasmic reticulum stress markers, were the highest in the HF + HFr combination group. Although intrahepatic fat deposition was less prominent in the HFr diet model, intrahepatic inflammation was noted. Conclusions. Intrahepatic inflammation and metabolic derangements were more prominent in the HF and HFr combination model than in the HF monodiet model.

  5. Carrot juice ingestion attenuates high fructose-induced circulatory pro-inflammatory mediators in weanling Wistar rats.

    Science.gov (United States)

    Mahesh, Malleswarapu; Bharathi, Munugala; Raja Gopal Reddy, Mooli; Pappu, Pranati; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

    2017-03-01

    Adipose tissue, an endocrine organ, plays a vital role not only in energy homeostasis, but also in the development and/or progression of various metabolic diseases, such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), via several factors and mechanisms, including inflammation. This study tested, whether carrot juice administration affected the adipose tissue development and its inflammatory status in a high fructose diet-induced rat model. For this purpose, male weanling Wistar rats were divided into four groups and fed either control or high fructose diet of AIN-93G composition with or without carrot juice ingestion for an 8 week period. Administration of carrot juice did not affect the adiposity and cell size of visceral fat depot; retroperitoneal white adipose tissue (RPWAT), which was corroborated with unaltered expression of genes involved in adipogenic and lipogenic pathways. However, it significantly reduced the high fructose diet-induced elevation of plasma free fatty acid (FFA) (P ≤ 0.05), macrophage chemoattractant protein 1 (MCP1) (P ≤ 0.01) and high sensitive C-reactive protein (hsCRP) (P ≤ 0.05) levels. Carrot juice administration attenuated the high fructose diet-induced elevation of levels of circulatory FFA and pro-inflammatory mediators; MCP1 and hsCRP without affecting the adiposity and cell size of visceral fat depot; RPWAT. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  6. Fish Oil Decreases Hepatic Lipogenic Genes in Rats Fasted and Refed on a High Fructose Diet

    Directory of Open Access Journals (Sweden)

    Gabriela S. de Castro

    2015-03-01

    Full Text Available Fasting and then refeeding on a high-carbohydrate diet increases serum and hepatic triacylglycerol (TAG concentrations compared to standard diets. Fructose is a lipogenic monosaccharide which stimulates de novo fatty acid synthesis. Omega-3 (n-3 fatty acids stimulate hepatic β-oxidation, partitioning fatty acids away from TAG synthesis. This study investigated whether dietary n-3 fatty acids from fish oil (FO improve the hepatic lipid metabolic response seen in rats fasted and then refed on a high-fructose diet. During the post-prandial (fed period, rats fed a FO rich diet showed an increase in hepatic peroxisome proliferator-activated receptor α (PPAR-α gene expression and decreased expression of carbohydrate responsive element binding protein (ChREBP, fatty acid synthase (FAS and microsomal triglyceride transfer protein (MTTP. Feeding a FO rich diet for 7 days prior to 48 h of fasting resulted in lower hepatic TAG, lower PPAR-α expression and maintenance of hepatic n-3 fatty acid content. Refeeding on a high fructose diet promoted an increase in hepatic and serum TAG and in hepatic PPAR-α, ChREBP and MTTP expression. FO did not prevent the increase in serum and hepatic TAG after fructose refeeding, but did decrease hepatic expression of lipogenic genes and increased the n-3 fatty acid content of the liver. n-3 Fatty acids can modify some components of the hepatic lipid metabolic response to later feeding with a high fructose diet.

  7. [Effects of rilmenidine on rats made insulin resistant and hypertensive by a high fructose diet].

    Science.gov (United States)

    Berthault, M F; Morin, J; Dubar, M; Ktorza, A; Ferré, P; Pénicaud, L

    1996-08-01

    This study was aimed to determine the effects of rilmenidine, an hypertensive drug, in an animal model of hypertension associated with insulin resistance, i.e. rats fed on a high fructose diet. Wistar rats were fed during four weeks either on a standard diet (S) or on a high fructose diet (F, 34.5% de fructose). In half of the F groups, rilmenidine (1 mg/kg/day) was added to the drinking water during the two last weeks of the diet (FR). Arterial blood pressure as well as insulin efficiency were determined at the end of the four weeks. Body weight gain was higher in F than in S rats (66 +/- 8 g versus 45 +/- 8 g; p metabolic disorders such as syndrom X and obesity.

  8. Dioscoreophyllum cumminsii (Stapf) Diels leaves halt high-fructose induced metabolic syndrome: Hyperglycemia, insulin resistance, inflammation and oxidative stress.

    Science.gov (United States)

    Ajiboye, T O; Aliyu, H; Tanimu, M A; Muhammad, R M; Ibitoye, O B

    2016-11-04

    Dioscoreophyllum cumminsii is widely used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous leaf extract of D. cumminsii on high-fructose diet-induced metabolic syndrome. Seventy male rats were randomized into seven groups. All rats were fed with high-fructose diet for 9 weeks except groups A and C rats, which received control diet. In addition to the diet treatment, groups A and B rats received distilled water for 3 weeks starting from the seventh week of the experimental period. Rats in groups C-F orally received 400, 100, 200 and 400mg/kg body weight of aqueous leaf extract of D. cumminsii respectively, while group G received 300mg/kg bodyweight of metformin for 3 weeks starting from the seventh week. There was significant (pinsulin, leptin and insulin resistance by aqueous leaf extract of D. cumminsii. Conversely, high-fructose diet-mediated decrease in adiponectin was reversed by the extract. Increased levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index were significantly lowered by the extract, while high-fructose diet mediated decrease in high-density lipoprotein cholesterol was increased by the extract. Tumour necrosis factor-α, interleukin-6 and interleukin-8 levels increased significantly in high-fructose diet-fed rats, which were significantly reversed by the extract. High-fructose mediated-decrease in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and glutathione reduced were significantly reversed by aqueous leaf extract of D. cumminsii. Conversely, elevated levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were significantly lowered by the extract. Data generated in this study further laid credence to the hypoglycemic activity of aqueous leaf extract

  9. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone

    Science.gov (United States)

    Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (03); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and th...

  10. Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet.

    Science.gov (United States)

    Hernández-Salinas, Romina; Decap, Valerie; Leguina, Alberto; Cáceres, Patricio; Perez, Druso; Urquiaga, Ines; Iturriaga, Rodrigo; Velarde, Victoria

    2015-09-30

    Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet. Male Sprague-Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C + WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA) index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thiobarbituric acid reactive substances (TBARS) level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney. Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups. Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.

  11. Aldosterone aggravates glucose intolerance induced by high fructose

    OpenAIRE

    Sherajee, Shamshad J.; Rafiq,Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira

    2013-01-01

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 μg/h, s.c., n=8), Unx+fructose (...

  12. Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

    Science.gov (United States)

    Hecker, Peter A.; Mapanga, Rudo F.; Kimar, Charlene P.; Ribeiro, Rogerio F.; Brown, Bethany H.; O'Connell, Kelly A.; Cox, James W.; Shekar, Kadambari C.; Asemu, Girma; Essop, M. Faadiel

    2012-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism. Oxidative stress may worsen systemic glucose tolerance and cardiometabolic syndrome. We hypothesized that G6PD deficiency exacerbates diet-induced systemic metabolic dysfunction by increasing oxidative stress but in myocardium prevents diet-induced oxidative stress and pathology. WT and G6PD-deficient (G6PDX) mice received a standard high-starch diet, a high-fat/high-sucrose diet to induce obesity (DIO), or a high-fructose diet. After 31 wk, DIO increased adipose and body mass compared with the high-starch diet but to a greater extent in G6PDX than WT mice (24 and 20% lower, respectively). Serum free fatty acids were increased by 77% and triglycerides by 90% in G6PDX mice, but not in WT mice, by DIO and high-fructose intake. G6PD deficiency did not affect glucose tolerance or the increased insulin levels seen in WT mice. There was no diet-induced hypertension or cardiac dysfunction in either mouse strain. However, G6PD deficiency increased aconitase activity by 42% and blunted markers of nonoxidative glucose pathway activation in myocardium, including the hexosamine biosynthetic pathway activation and advanced glycation end product formation. These results reveal a complex interplay between diet-induced metabolic effects and G6PD deficiency, where G6PD deficiency decreases weight gain and hyperinsulinemia with DIO, but elevates serum free fatty acids, without affecting glucose tolerance. On the other hand, it modestly suppressed indexes of glucose flux into nonoxidative pathways in myocardium, suggesting potential protective effects. PMID:22829586

  13. Aldosterone aggravates glucose intolerance induced by high fructose.

    Science.gov (United States)

    Sherajee, Shamshad J; Rafiq, Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira

    2013-11-15

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation. © 2013 Published by Elsevier B.V.

  14. The effect of high-fat--high-fructose diet on skeletal muscle mitochondrial energetics in adult rats.

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Coppola, Paola; Mazzoli, Arianna; Cigliano, Luisa; Liverini, Giovanna; Iossa, Susanna

    2015-03-01

    To study the effect of isoenergetic administration to adult rats of high-fat or high-fat--high-fructose diet for 2 weeks on skeletal muscle mitochondrial energetic. Body and skeletal muscle composition, energy balance, plasma lipid profile and glucose tolerance were measured, together with mitochondrial functionality, oxidative stress and antioxidant defense. Rats fed high-fat--high-fructose diet exhibited significantly higher plasma triglycerides and non-esterified fatty acids, together with significantly higher plasma glucose and insulin response to glucose load. Skeletal muscle triglycerides and ceramide were significantly higher in rats fed high-fat--high-fructose diet. Skeletal muscle mitochondrial energetic efficiency and uncoupling protein 3 content were significantly higher, while adenine nucleotide translocase content was significantly lower, in rats fed high-fat or high-fat--high-fructose diet. The results suggest that a high-fat--high-fructose diet even without hyperphagia is able to increase lipid flow to skeletal muscle and mitochondrial energetic efficiency, with two detrimental effects: (a) energy sparing that contributes to the early onset of obesity and (b) reduced oxidation of fatty acids and lipid accumulation in skeletal muscle, which could generate insulin resistance.

  15. Lactoferrin Dampens High-Fructose Corn Syrup-Induced Hepatic Manifestations of the Metabolic Syndrome in a Murine Model

    Science.gov (United States)

    Li, Yi-Chieh; Hsieh, Chang-Chi

    2014-01-01

    Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome. PMID:24816278

  16. The protective role of low-concentration alcohol in high-fructose induced adverse cardiovascular events in mice.

    Science.gov (United States)

    Wu, Xiaoqi; Pan, Bo; Wang, Ying; Liu, Lingjuan; Huang, Xupei; Tian, Jie

    2018-01-01

    Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice. From the results of hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and the expression of hypertrophic marker ANP, we found high-fructose result in myocardial hypertrophy and the low-concentration alcohol consumption would prevent the cardiomyocyte hypertrophy from happening. In addition, we observed low-concentration alcohol consumption could inhibit mitochondria swollen induced by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol in high-fructose group were reduced by low concentration alcohol. Low expression levels of SIRT1 and PPAR-γ induced by high-fructose were significantly elevated when fed with low-concentration alcohol. The histone lysine 9 acetylation (acH3K9) level was decreased in PPAR-γ promoter in high-fructose group but elevated when intake with low concentration alcohol. The binding levels of histone deacetylase SIRT1 were increased in the same region in high-fructose group, while the low concentration alcohol can prevent the increased binding levels. Overall, our study indicates that low-concentration alcohol consumption could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria damaged and disorders of glucose-lipid metabolism. Furthermore, these findings also provide new insights into histone acetylation-deacetylation mechanisms of low-concentration alcohol treatment that may contribute to the prevention of cardiovascular disease induced by high-fructose

  17. Methanol extract of Sorbus commixta cortex prevents vascular inflammation in rats with a high fructose-induced metabolic syndrome.

    Science.gov (United States)

    Kang, Dae Gill; Sohn, Eun Jin; Lee, An Sook; Kim, Jin Sook; Lee, Dae Ho; Lee, Ho Sub

    2007-01-01

    Feeding high fructose (Frc) to rats induces a moderate increase in blood pressure, which is associated with insulin resistance. The present study was designed to evaluate the effect of the methanol extract of Sorbus commixta cortex (MSC) on vascular inflammation in a rat model of the metabolic syndrome induced by a high Frc-diet. Male Sprague-Dawley rats were divided into 4 groups and treated for 7 weeks as follows: 1) control, 2) high Frc-diet group, 3) Frc/MSC1 group; high Frc-diet group treated with MSC (100 mg/kg/day), and 4) Frc/MSC2 group; high Frc-diet group treated with MSC (200 mg/kg/day). High Frc-induced decreases of the expression level of aortic endothelial nitric oxide synthase (ecNOS) while the production of cyclic GMP (cGMP) was restored by treatment with MSC. On the contrary, increases of the expression level of endothelin-1 (ET-1) in the aorta, the transcription factor, the cytokine related with vascular inflammation, and the adhesion molecules were suppressed by MSC treatment. Moreover, MSC treatment was shown to lessen the thickening noted in the aortic intima and media of the high Frc-diet group. Our findings suggest that MSC may have an anti-vascular inflammatory effect on rats with a high Frc-induced metabolic syndrome.

  18. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone

    Data.gov (United States)

    U.S. Environmental Protection Agency — pulmonary parameters, BALF biomarkers, body composition, motor activity data collected from rats exposed to ozone after high fructose or high fat diets. This dataset...

  19. Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats.

    Science.gov (United States)

    Mahesh, Malleswarapu; Bharathi, Munugala; Reddy, Mooli Raja Gopal; Kumar, Manchiryala Sravan; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

    2016-09-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and β-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.

  20. Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet.

    Science.gov (United States)

    Huang, Da-Wei; Chang, Wen-Chang; Wu, James Swi-Bea; Shih, Rui-Wen; Shen, Szu-Chuan

    2016-02-01

    Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 μg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress.

    Science.gov (United States)

    Balakumar, M; Raji, L; Prabhu, D; Sathishkumar, C; Prabu, P; Mohan, V; Balasubramanyam, M

    2016-12-01

    In the context of high human consumption of fructose diets, there is an imperative need to understand how dietary fructose intake influence cellular and molecular mechanisms and thereby affect β-cell dysfunction and insulin resistance. While evidence exists for a relationship between high-fat-induced insulin resistance and metabolic disorders, there is lack of studies in relation to high-fructose diet. Therefore, we attempted to study the effect of different diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats compared to control animals fed with normal pellet diet. Investigations include oral glucose tolerance test, insulin tolerance test, histopathology by H&E and Masson's trichrome staining, mRNA expression by real-time PCR, protein expression by Western blot, and caspase-3 activity by colorimetry. Rats subjected to high-fat/fructose diets became glucose intolerant, insulin-resistant, and dyslipidemic. Compared to control animals, rats subjected to different combination of fat/fructose diets showed increased mRNA and protein expression of a battery of ER stress markers both in pancreas and liver. Transcription factors of β-cell function (INSIG1, SREBP1c and PDX1) as well as hepatic gluconeogenesis (FOXO1 and PEPCK) were adversely affected in diet-induced insulin-resistant rats. The convergence of chronic ER stress towards apoptosis in pancreas/liver was also indicated by increased levels of CHOP mRNA & increased activity of both JNK and Caspase-3 in rats subjected to high-fat/fructose diets. Our study exposes the experimental support in that high-fructose diet is equally detrimental in causing metabolic disorders.

  2. Effect of skim milk and dahi (yogurt) on blood glucose, insulin, and lipid profile in rats fed with high fructose diet.

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    Yadav, Hariom; Jain, Shalini; Sinha, P R

    2006-01-01

    In the present study, the effect of skim milk and the fermented milk product named dahi (yogurt) on plasma glucose, insulin, and lipid levels as well as on liver glycogen and lipid contents in rats fed with high fructose diet has been investigated. Rats were fed with high fructose diet (21%) supplemented with skim milk, dahi (10 g/day each), or no milk product (control group) for 6 weeks. After 6 weeks of high fructose diet administration, the plasma glucose became significantly higher in control animals (246 mg/dL), whereas it was lower in skim milk (178 mg/dL)- and dahi (143 mg/dL)-fed rats. The glucose tolerance became impaired at the third week of feeding of high fructose diet in control animals, whereas in skim milk- and dahi-fed animals achievement of glucose intolerance was delayed until the fourth and fifth week, respectively. Blood glycosylated hemoglobin and plasma insulin were significantly lower in skim milk (10% and 34%, respectively)- and dahi (17%, and 48%, respectively)-fed animals than those of the control group. Plasma total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and very-low-density lipoprotein-cholesterol and blood free fatty acids were significantly lower in skim milk (13%, 14%, 14%, 19%, and 14%, respectively)- and dahi (22%, 33%, 30%, 33%, and 29%, respectively)-fed animals as compared with control animals. Moreover, the total cholesterol, triglyceride, and glycogen contents in liver tissues were also lower in skim milk (55%, 50%, and 36%, respectively)- and dahi (64%, 27%, and 4%, respectively)-fed animals as compared with control animals. In contrast, high-density lipoprotein-cholesterol in plasma was higher in skim milk (14%)- and dahi (29%)-fed animals as compared with control animals. These results indicate that skim milk and its fermented milk product, dahi, delay the progression of fructose-induced diabetes and dyslipidemia in rats and that these may be useful as antidiabetic food supplements that can be

  3. Reduced-calorie avocado paste attenuates metabolic factors associated with a hypercholesterolemic-high fructose diet in rats.

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    Pahua-Ramos, María Elena; Garduño-Siciliano, Leticia; Dorantes-Alvarez, Lidia; Chamorro-Cevallos, German; Herrera-Martínez, Julieta; Osorio-Esquivel, Obed; Ortiz-Moreno, Alicia

    2014-03-01

    The objective of this study was to evaluate the effect of reduced-calorie avocado paste on lipid serum profile, insulin sensitivity, and hepatic steatosis in rats fed a hypercholesterolemic-high fructose diet. Thirty five male Wistar rats were randomly separated in five groups: Control group (ground commercial diet); hypercholesterolemic diet plus 60% fructose solution (HHF group); hypercholesterolemic diet plus 60% fructose solution supplemented with avocado pulp (HHF+A group); hypercholesterolemic diet plus 60% fructose solution supplemented with reduced-calorie avocado paste (HHF+P group); and hypercholesterolemic diet plus 60% fructose solution supplemented with a reduced-calorie avocado paste plus fiber (HHF+FP group). The A, P, and FP were supplemented at 2 g/kg/d. The study was carried out for seven weeks. Rats belonging to the HHF group exhibited significantly (P ≤ 0.05) higher total cholesterol, triglycerides, and insulin levels in serum as well as lower insulin sensitivity than the control group. Supplementation with reduced-calorie avocado paste showed a significant (P ≤ 0.05) decrease in total cholesterol (43.1%), low-density lipoprotein (45.4%), and triglycerides (32.8%) in plasma as well as elevated insulin sensitivity compared to the HHF group. Additionally, the liver enzymes alanine aminotransferase and aspartate aminotransferase decreased significantly in the HHF-P group (39.8 and 35.1%, respectively). These results are likely due to biocompounds present in the reduced-calorie avocado paste, such as polyphenols, carotenoids, chlorophylls, and dietary fibre, which are capable of reducing oxidative stress. Therefore, reduced-calorie avocado paste attenuates the effects of a hypercholesterolemic-high fructose diet in rats.

  4. Effects of high fructose diets on central appetite signaling and cognitive function

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    Katrien eLowette

    2015-03-01

    Full Text Available The consumption of fructose has increased tremendously over the last five decades, which is to a large extent due to the development of high fructose corn syrup (HFCS, a commercial sugar additive that contains high amounts of free fructose. HFCS is often added to processed food and beverages partly because it is a powerful sweetener but even more so because the production is cheap. Although fructose in combination with fiber, vitamins and minerals, as present in fruits, is a healthy source of energy, isolated fructose, in processed food products has been associated with several health disorders such as insulin resistance and hypertension. Apart from its metabolic consequences, a growing body of literature suggests that free fructose can also affect neuronal systems. High fructose intake may on the one hand affect central appetite regulation by altering specific components of the endocannabinoid system. On the other hand it appears to impact on cognitive function by affecting phosphorylation levels of insulin receptor, synapsin 1 and synaptophysin. The present report reviews the recent evidence showing a negative effect of free fructose consumption on central appetite control, as well as cognitive function.

  5. Long-term feeding of red algae (Gelidium amansii ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model

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    Hshuan-Chen Liu

    2017-07-01

    Full Text Available This study was designed to investigate the effect of Gelidium amansii (GA on carbohydrate and lipid metabolism in rats with high fructose (HF diet (57.1% w/w. Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1 control diet group (Con; (2 HF diet group (HF; and (3 HF with GA diet group (HF + 5% GA. The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model.

  6. Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model.

    Science.gov (United States)

    Liu, Hshuan-Chen; Chang, Chun-Ju; Yang, Tsung-Han; Chiang, Meng-Tsan

    2017-07-01

    This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model. Copyright © 2016. Published by Elsevier B.V.

  7. Eicosapentaenoic acid (EPA) vs. Docosahexaenoic acid (DHA): Effects in epididymal white adipose tissue of mice fed a high-fructose diet.

    Science.gov (United States)

    Bargut, Thereza Cristina Lonzetti; Santos, Larissa Pereira; Machado, Daiana Guimarães Lopes; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

    2017-08-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to be beneficial for many diseases, including those associated with the metabolic syndrome (e.g. insulin resistance and hypertension). Nevertheless, not only their actions are not entirely understood, but also their only effects were not yet elucidated. Therefore, we aimed to compare the effects of EPA and DHA, alone or in combination, on the epididymal white adipose tissue (WAT) metabolism in mice fed a high-fructose diet. 3-mo-old C57Bl/6 mice were fed a control diet (C) or a high-fructose diet (HFru). After three weeks on the diets, the HFru group was subdivided into four new groups for another five weeks: HFru, HFru+EPA, HFru+DHA, and HFru-EPA+DHA (n=10/group). Besides evaluating biometric and metabolic parameters of the animals, we measured the adipocyte area and performed molecular analyses (inflammation and lipolysis) in the epididymal WAT. The HFru group showed adipocyte hypertrophy, inflammation, and uncontrolled lipolysis. The treated animals showed a reversion of adipocyte hypertrophy, inhibition of inflammation with activation of anti-inflammatory mediators, and regularization of lipolysis. Overall, the beneficial effects were more marked with DHA than EPA. Although the whole-body metabolic effects were similar between EPA and DHA, DHA appeared to be the central actor in WAT metabolism, modulating pro and anti-inflammatory pathways and alleviating adipocytes abnormalities. Therefore, when considering fructose-induced adverse effects in WAT, the most prominent actions were observed with DHA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone

    Science.gov (United States)

    pulmonary parameters, BALF biomarkers, body composition, motor activity data collected from rats exposed to ozone after high fructose or high fat diets.This dataset is associated with the following publication:Gordon , C., P. Phillips , A. Johnstone , T. Beasley , A. Ledbetter , M. Schladweiler , S. Snow, and U. Kodavanti. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, USA, 28(5): 203-15, (2016).

  9. Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet.

    Science.gov (United States)

    Huang, Da-Wei; Chang, Wen-Chang; Wu, James Swi-Bea; Shih, Rui-Wen; Shen, Szu-Chuan

    2016-02-10

    This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up-regulated the expression of hepatic glycogen synthase and hepatic glycolysis-related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus.

  10. Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes.

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    Richard A Anderson

    Full Text Available Insulin resistance leads to memory impairment. Cinnamon (CN improves peripheral insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain were measured in male Wistar rats fed a high fat/high fructose (HF/HFr diet to induce insulin resistance, with or without CN, for 12 weeks. There was a decrease in insulin sensitivity associated with the HF/HFr diet that was reversed by CN. The CN fed rats were more active in a Y maze test than rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. The HF/HFr diet also led to a down regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the hippocampus and cortex due to the HF/HFr diet that were not reversed by CN. Increased peripheral insulin sensitivity was also associated with increased glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet animals fed CN. The HF/HFr diet induced increases in mRNA associated with Alzheimers including PTEN, Tau and amyloid precursor protein (App were also alleviated by CN. In conclusion, these data suggest that the negative effects of a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated changes were alleviated by CN suggesting that neuroprotective effects of CN are associated with improved whole body insulin sensitivity and related changes in the brain.

  11. A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice

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    Zhuhua, Zhang; Zhiquan, Wang; Zhen, Yang; Yixin, Niu; Weiwei, Zhang; Xiaoyong, Li; Yueming, Liu; Hongmei, Zhang; Li, Qin; Qing, Su

    2015-01-01

    Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS. PMID:26134356

  12. A colorimetric method for lysyl oxidase activity in copper deficient rats fed a high fructose diet

    Energy Technology Data Exchange (ETDEWEB)

    Werman, M.J.; Bhathena, S.J. (Dept. of Agriculture, Beltsville, MD (United States))

    1991-03-11

    Lysyl oxidase is involved in initiating cross link formation in collagen and elastin. The activity of lysyl oxidase is traditionally assessed by the tritium released assay. The authors describe a simplified and modified method for measuring lysyl oxidase activity in rats, based on measuring ammonia release according to the Bertholet colorimetric reaction. Lysyl oxidase activity was measured in copper deficient rats using this method. Sixteen weanling Sprague Dawley male rats were fed for four weeks either copper adequate or copper deficient diets containing 62% fructose. Copper deficiency was confirmed by significant low copper levels in heart, brain, liver and skin, and by nondetectable levels of ceruloplasmin. Lysyl oxidase activity was significantly lower in heart and skin of rats fed a copper deficient diet compared to those fed a copper adequate diet. No significant difference in activity was observed in brain tissue. A correlation was not observed between decreased tissue copper levels and decreased lysyl oxidase activity. Thus, the determination of ammonia liberated during lysyl oxidase activity may serve as an effective tool in assessing lysyl oxidase activity.

  13. Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report

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    Alexandre-Gouabau, Marie Cécile; Pagniez, Anthony; Ouguerram, Khadija; Boquien, Clair; WINER, Norbert; Darmaun, Dominique

    2017-01-01

    A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown. LBW pups born from dams fed a low (4%) protein diet, were nursed by normally-fed dams and received isonitrogenous supplements of either l-citrulli...

  14. Endothelial dysfunction in high fructose containing diet fed rats: Increased nitric oxide and decreased endothelin-1 levels in liver tissue

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    Zeki Arı

    2010-09-01

    Full Text Available Objectives: Dietary high fructose consumption which is closely associated with endothelial dysfunction via insulin re-sistance has recently increased in developed countries. Insulin resistance has a promoter effect on many metabolic disorders such as syndrome X, polycystic ovary syndrome, Type 2 diabetes mellitus etc. Our aim in this study is to understand the impact of increased fructose intake on metabolisms of glucose, insulin and endothelial dysfunction by measuring nitric oxide (NO and endothelin-1 (ET-1 levels in hepatic tissue which is crucial in fructose metabolism.Materials and Methods: We designed an animal study to understand increased fructose intake on hepatic endothe-lium. Twenty adult male albino rats were divided into two groups; the study group (group 1, n=10 received isocaloric fructose enriched diet (fructose-fed rats, containing 18.3% protein, 60.3% fructose and 5.2% fat while the control group received purified regular chow (group 2, n=10 for 2 weeks. After feeding period, blood and hepatic tissue samples were collected and glucose, insulin, NO and ET-1 levels were analysed.Results: We found increased fasting glucose and insulin levels and impaired glucose tolerance in fructose fed rats. Higher NO and lower ET–1 levels were also detected in hepatic tissue samples of the group 1.Conclusion: Increased fructose consumption has deleterious effects on glucose tolerance, insulin resistance and may cause to endothelial dysfunction.

  15. Oat beta-glucan ameliorates insulin resistance in mice fed on high-fat and high-fructose diet

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    Jie Zheng

    2013-12-01

    Full Text Available Methods: This study sought to evaluate the impact of oat beta-glucan on insulin resistance in mice fed on high-fat and high-fructose diet with fructose (10%, w/v added in drinking water for 10 weeks. Results: The results showed that supplementation with oat beta-glucan could significantly reduce the insulin resistance both in low-dose (200 mg/kg−1 body weight and high-dose (500 mg/kg−1 body weight groups, but the high-dose group showed a more significant improvement in insulin resistance (P<0.01 compared with model control (MC group along with significant improvement in hepatic glycogen level, oral glucose, and insulin tolerance. Moreover, hepatic glucokinase activity was markedly enhanced both in low-dose and high-dose groups compared with that of MC group (P<0.05. Conclusion: These results suggested that supplementation of oat beta-glucan alleviated insulin resistance and the effect was dose dependent.

  16. Postprandial fatty acid uptake and adipocyte remodeling in angiotensin type 2 receptor-deficient mice fed a high-fat/high-fructose diet.

    Science.gov (United States)

    Noll, Christophe; Labbé, Sébastien M; Pinard, Sandra; Shum, Michael; Bilodeau, Lyne; Chouinard, Lucie; Phoenix, Serge; Lecomte, Roger; Carpentier, André C; Gallo-Payet, Nicole

    2016-01-01

    The role of the angiotensin type-2 receptor in adipose physiology remains controversial. The aim of the present study was to demonstrate whether genetic angiotensin type-2 receptor-deficiency prevents or worsens metabolic and adipose tissue morphometric changes observed following a 6-week high-fat/high-fructose diet with injection of a small dose of streptozotocin. We compared tissue uptake of nonesterified fatty acid and dietary fatty acid in wild-type and angiotensin type-2 receptor-deficient mice by using the radiotracer 14(R,S)-[(1) (8)F]-fluoro-6-thia-heptadecanoic acid in mice fed a standard or high-fat diet. Postprandial fatty acid uptake in the heart, liver, skeletal muscle, kidney and adipose tissue was increased in wild-type mice after a high-fat diet and in angiotensin type-2 receptor-deficient mice on both standard and high-fat diets. Compared to the wild-type mice, angiotensin type-2 receptor-deficient mice had a lower body weight, an increase in fasting blood glucose and a decrease in plasma insulin and leptin levels. Mice fed a high-fat diet exhibited increased adipocyte size that was prevented by angiotensin type-2 receptor-deficiency. Angiotensin type-2 receptor-deficiency abolished the early hypertrophic adipocyte remodeling induced by a high-fat diet. The small size of adipocytes in the angiotensin type-2 receptor-deficient mice reflects their inability to store lipids and explains the increase in fatty acid uptake in non-adipose tissues. In conclusion, a genetic deletion of the angiotensin type-2 receptor is associated with metabolic dysfunction of white adipose depots, and indicates that adipocyte remodeling occurs before the onset of insulin resistance in the high-fat fed mouse model.

  17. High fructose intake fails to induce symptomatic adaptation but may induce intestinal carriers

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    Debra Heilpern

    2010-01-01

    Full Text Available Fructose has several interactions in man, including intolerance and promotion of some diseases. However, fructose in fruits and in prebiotics may be associated with benefits. Adaptation to regular fructose ingestion as defined for lactose could support a beneficial rather than a deleterious effect. This study was undertaken to evaluate symptomatic response and potential underlying mechanisms of fecal bacterial change and breath hydrogen response to short term regular fructose supplementation. Forty-five participants were recruited for a 3 day recall diet questionnaire and a 50 g fructose challenge. Breath hydrogen was measured for 4.5 hrs and symptoms were recorded. Thirty-eight subjects provided stool samples for analysis by selective culture of 4 groups of bacteria, including bifidobacteria and lactobacilli. Intolerant subjects returned a second time 15 days later. Ten of these served as controls and 16 received 30 g fructose twice a day. Ten of the latter returned 27 days later, after stopping fructose for a third challenge test. Student’s paired, unpaired t-tests and Pearson correlations were used. Significance was accepted at P<0.05. After fructose rechallenge there were no significant reductions in symptoms scores in volunteers in either the fructose supplemented or non supplemented groups. However, total breath hydrogen was reduced between test 1 and test 2 (P=0.03 or test 3 (P=0.04 in the group given fructose then discontinued, compared with controls. There were no statistically significant changes in bacterial numbers between test 2 and 1. This study shows that regular consumption of high dose fructose does not follow the lactose model of adaptation. Observed changes in hydrogen breath tests raise the possibility that intestinal carriers of fructose may be induced potentially aggravating medical problems attributed to fructose.

  18. Polyphenols from hawthorn peels and fleshes differently mitigate dyslipidemia, inflammation and oxidative stress in association with modulation of liver injury in high fructose diet-fed mice.

    Science.gov (United States)

    Han, Xiao; Li, Wenfeng; Huang, Di; Yang, Xingbin

    2016-09-25

    Hawthorn ingestion is linked to health benefits due to the various polyphenols. The present study investigated the differential effects of polyphenols-enriched extracts from hawthorn fruit peels (HPP) and fleshes (HFP) against liver injury induced by high-fructose diet in mice. It was found that the main species of polyphenols in hawthorn was chlorogenic acid, epicatechin, rutin and hyperoside, and their contents in HPP were all higher than those in HFP. Administration of HPP was better than HFP to alleviate liver injury and hepatocyte apoptosis, reflected by the reduction of ALT, AST and ALP activities, as well as the ratio of Bax/Bcl-2 in mice. Meanwhile, HPP was also more effective than HFP to mitigate liver inflammation and oxidative stress by inhibiting inflammatory cytokine (TNF-α, IL-1 and IL-6) release, and elevating antioxidant enzyme activities and PPARα expression, while reducing Nrf-2 and ARE expression in mice. Interestingly, HPP-treated mice also showed the lower levels of TC, TG, LDL-C, VLDL-C and Apo-B, and the higher levels of HDL-C and Apo-A1 than HFP-treated mice via reducing FAS express. These results together with the histopathology of the liver with H&E and oil red O staining suggest that hawthorn fruit, especially its peel, is an excellent source of natural polyphenolic chemopreventive agents in the treatment of liver disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Similar changes in muscle lipid metabolism are induced by chronic high-fructose feeding and high-fat feeding in C57BL/J6 mice.

    Science.gov (United States)

    Song, Guang-Yao; Ren, Lu-Ping; Chen, Shu-Chun; Wang, Chao; Liu, Na; Wei, Li-Min; Li, Fan; Sun, Wen; Peng, Lan-Bo; Tang, Yong

    2012-12-01

    The aim of the present study was to investigate the effects of high fructose and high fat feeding on muscle lipid metabolism and to illustrate the mechanisms by which the two different dietary factors induce muscle lipid accumulation. C57BL/J6 mice were fed either a standard, high-fructose (HFru) or high-fat diet. After 16 weeks feeding, mice were killed and plasma triglyceride (TG) and free fatty acid (FFA) levels were detected. In addition, muscle TG and long chain acyl CoA (LCACoA) content was determined, glucose tolerance was evaluated and the protein content of fatty acid translocase CD36 (FATCD36) in muscle was measured. Mitochondrial oxidative function in the muscle was evaluated by estimating the activity of oxidative enzymes, namely cytochrome oxidase (COx), citrate synthase (CS) and β-hydroxyacyl CoA dehydrogenase (β-HAD), and the muscle protein content of carnitine palmitoyltransferase-1 (CPT-1), cyclo-oxygenase (COX)-1 and proliferator-activated receptor coactivator (PGC)-1α was determined. Finally, sterol regulatory element-binding protein-1c (SREBP-1c) gene expression and fatty acid synthase (FAS) protein content were determined in muscle tissues. After 16 weeks, plasma TG and FFA levels were significantly increased in both the HFru and HF groups. In addition, mice in both groups exhibited significant increases in muscle TG and LCACoA content. Compared with mice fed the standard diet (control group), those in the HFru and HF groups developed glucose intolerance and exhibited increased FATCD36 protein levels, enzyme activity related to fatty acid utilization in the mitochondria and protein expressions of CPT-1, COX-1 and PGC-1α in muscle tissue. Finally, mice in both the HFru and HF groups exhibited increase SREBP-1c expression and FAS protein content. In conclusion, high fructose and high fat feeding lead to similar changes in muscle lipid metabolism in C57BL/J6 mice. Lipid accumulation in the muscle may be associated with increased expression

  20. The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters

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    Lowndes Joshua

    2012-08-01

    Full Text Available Abstract Background The replacement of sucrose with HFCS in food products has been suggested as playing a role in the development of obesity as a public health issue. The objective of this study was to examine the effects of four equally hypocaloric diets containing different levels of sucrose or high fructose corn syrup (HFCS. Methods This was a randomized, prospective, double blind trial, with overweight/obese participants measured for body composition and blood chemistry before and after the completion of 12 weeks following a hypocaloric diet. The average caloric deficit achieved on the hypocaloric diets was 309 kcal. Results Reductions were observed in all measures of adiposity including body mass, BMI,% body fat, waist circumference and fat mass for all four hypocaloric groups, as well as reductions in the exercise only group for body mass, BMI and waist circumference. Conclusions Similar decreases in weight and indices of adiposity are observed when overweight or obese individuals are fed hypocaloric diets containing levels of sucrose or high fructose corn syrup typically consumed by adults in the United States.

  1. Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report.

    Science.gov (United States)

    Tran, Nhat-Thang; Alexandre-Gouabau, Marie-Cécile; Pagniez, Anthony; Ouguerram, Khadija; Boquien, Clair-Yves; Winer, Norbert; Darmaun, Dominique

    2017-04-11

    A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown. LBW pups born from dams fed a low (4%) protein diet, were nursed by normally-fed dams and received isonitrogenous supplements of either l-citrulline or l-alanine by gavage from the sixth day of life until weaning, and were subsequently exposed to 10%-fructose in drinking water from weaning to 90 days of age. The oral glucose tolerance was tested (OGTT) at 70 days of age, and rats were sacrificed at 90 days of age. Pre-weaning citrulline supplementation failed to alter the growth trajectory, OGTT, plasma triglycerides, or fat mass accretion in adulthood; yet, it was associated with increased liver triglycerides, decreased liver total cholesterol, and a distinct liver lipidomic profile that may result in a predisposition to liver disease. We conclude that pre-weaning supplementation with citrulline does not impact early growth, but might impact liver fat metabolism in adulthood upon exposure to a high fructose diet.

  2. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

    Directory of Open Access Journals (Sweden)

    Cariou Bertrand

    2013-01-01

    Full Text Available Abstract Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9 is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2 and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D patients that are more prone to develop insulin resistance, including: i acute post-prandial hyperlipidemic challenge (n=10, ii 4 days of high-fat (HF or high-fat/high-protein (HFHP (n=10, iii 7 (HFruc1, n=16 or 6 (HFruc2, n=9 days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1. Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05 in healthy volunteers and by 34% (p=0.001 in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p Conclusions Plasma PCSK9 concentrations vary

  3. Effect of quinoa seeds (Chenopodium quinoa) in diet on some biochemical parameters and essential elements in blood of high fructose-fed rats.

    Science.gov (United States)

    Paśko, Paweł; Zagrodzki, Paweł; Bartoń, Henryk; Chłopicka, Joanna; Gorinstein, Shela

    2010-12-01

    The effect of Chenopodium quinoa seeds on lipid profile, glucose level, protein metabolism and selected essential elements (Na, K, Ca, Mg) level was determined in high-fructose fed male Wistar rats. Fructose decreased significantly LDL [42%, pquinoa indicated, that these seeds effectively reduced serum total cholesterol [26%, pQuinoa seeds also significantly reduced the level of glucose [10%, pquinoa seeds were added into the diet the decrease of HDL level was inhibited. Quinoa seeds did not prevent any adverse effect of increasing triglyceride level caused by fructose. It was shown in this study that quinoa seeds can reduce most of the adverse effects exerted by fructose on lipid profile and glucose level.

  4. HYPOGLYCEMIC EFFECT OF 2-HYDROXYCHALCONE ON HIGH FRUCTOSE FED DIABETIC RAT

    OpenAIRE

    K. Jegatheesan et al.

    2012-01-01

    The objective of the project work was to study the effect of Hypoglycemic and Hypolipidemic activity of 2- hydroxychalcone on high fructose diet induced insulin resistance in male Wister Albino rats. Rats were rendered insulin resistant by feeding 66% (w/w) fructose and 1.1% (v/w) coconut oil mixed with normal pellet diet (NPD) for 3 weeks. Insulin resistance high fructose diabetic rats receiving hydroxychalcone intraperitoneally (i.p.) at the dose of 25mg/kg body weight daily for 7 consecuti...

  5. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats.

    Science.gov (United States)

    Yadav, Hariom; Jain, Shalini; Sinha, P R

    2007-01-01

    We investigated the effect of low-fat (2.5%) dahi containing probiotic Lactobacillus acidophilus and Lactobacillus casei on progression of high fructose-induced type 2 diabetes in rats. Diabetes was induced in male albino Wistar rats by feeding 21% fructose in water. The body weight, food and water intakes, fasting blood glucose, glycosylated hemoglobin, oral glucose tolerance test, plasma insulin, liver glycogen content, and blood lipid profile were recorded. The oxidative status in terms of thiobarbituric acid-reactive substances and reduced glutathione contents in liver and pancreatic tissues were also measured. Values for blood glucose, glycosylated hemoglobin, glucose intolerance, plasma insulin, liver glycogen, plasma total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and blood free fatty acids were increased significantly after 8 wk of high fructose feeding; however, the dahi-supplemented diet restricted the elevation of these parameters in comparison with the high fructose-fed control group. In contrast, high-density lipoprotein cholesterol decreased slightly and was retained in the dahi-fed group. The dahi-fed group also exhibited lower values of thiobarbituric acid-reactive substances and higher values of reduced glutathione in liver and pancreatic tissues compared with the high fructose-fed control group. The probiotic dahi-supplemented diet significantly delayed the onset of glucose intolerance, hyperglycemia, hyperinsulinemia, dyslipidemia, and oxidative stress in high fructose-induced diabetic rats, indicating a lower risk of diabetes and its complications.

  6. Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway

    OpenAIRE

    H.L. Chen; Tsai, T C; Tsai, Y C; Liao, J W; Yen, C. C.; Chen, C.M.

    2016-01-01

    Objective: In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides o...

  7. Effects of salicylic acid-induced wine rich in anthocyanins on metabolic parameters and adipose insulin signaling in high-fructose fed rats.

    Science.gov (United States)

    Rodriguez Lanzi, Cecilia; de Rosas, Inés; Perdicaro, Diahann J; Ponce, María Teresa; Martinez, Liliana; Miatello, Roberto M; Cavagnaro, Bruno; Vazquez Prieto, Marcela A

    2016-12-01

    We evaluated the effects of Syrah red wine treated with salicylic acid (RW SA) and its control red wine (RW) on metabolic parameters, systolic blood pressure and adipose tissue insulin signaling in high-fructose (F) fed rats. Grape treated with SA increased the anthocyanin (ANTs) levels in RW. F induced increased systolic blood pressure, dislipidemia and insulin resistance (HOMA:IR). F rats treated with RW significantly prevented these alterations while RW SA partially attenuated triglycerides levels and HOMA:IR without modifications in HDL cholesterol levels. F impaired the adipose tissue response to insulin. Supplementation with RW and RW SA partially attenuated these alterations. Rats supplemented with RW SA had lesser beneficial effects on metabolic alterations than control RW, while both RW and RW SA attenuated altered adipose response to insulin. More studies are necessary to deeply evaluate the effect on SA-induced RW rich in ANTs levels on metabolic alterations associated to MetS.

  8. Genistein sensitizes hepatic insulin signaling and modulates lipid regulatory genes through p70 ribosomal S6 kinase-1 inhibition in high-fat-high-fructose diet-fed mice.

    Science.gov (United States)

    Arunkumar, Elumalai; Karthik, Dhanapalan; Anuradha, Carani Venkatraman

    2013-07-01

    Genistein reduces high-calorie diet-induced insulin resistance and fat accumulation in animals, but the mechanism is unresolved. This study explores whether action of genistein is associated with p70 ribosomal S6 kinase-1 (S6K1) inhibition. Adult male mice were fed either normal diet or high-fat-high-fructose diet (HFFD) for 15 days, after which animals in each dietary group were divided into two groups and administered either genistein (1 mg kg(-1) day(-1), p.o.) in 0.5 ml of 30% dimethylsulfoxide (DMSO) or 30% DMSO (0.5 ml) for the next 45 days. At the end of the study, their liver was analyzed for lipid content. Semi-quantitative RT-PCR and western blotting methods were used to analyze lipid regulatory genes and insulin signaling proteins, respectively. Genistein significantly (p lipid levels. Histology showed a 2.5-fold increase of lipid in HFFD compared to control. Genistein treatment to HFFD-fed animals significantly decreased lipid accumulation (by 40%) compared to HFFD. Insulin-stimulated tyrosine phosphorylation of insulin receptor-β and insulin receptor substrates-1 (IRS-1), IRS-1 associated phospatidylinositol-3kinase (PI3K) and Akt Ser(473) phosphorylation were improved while IRS-1 serine phosphorylation was significantly (p increase in adenosine monophosphate-activated protein kinase (AMPK) Thr(172) phosphorylation and decrease in S6K1 Thr(389) phosphorylation were observed in HFFD-plus genistein compared to HFFD. Genistein downregulated lipogenic genes and upregulated fatty acid oxidative genes in HFFD-fed mice. Genistein improves insulin signaling and attenuates fat accumulation in liver through S6K1 inhibition.

  9. High-fructose diet downregulates long-chain acyl-CoA synthetase 3 expression in liver of hamsters via impairing LXR/RXR signaling pathway.

    Science.gov (United States)

    Dong, Bin; Kan, Chin Fung Kelvin; Singh, Amar B; Liu, Jingwen

    2013-05-01

    Long-chain acyl-CoA synthetases (ACSL) play key roles in fatty acid metabolism in liver and other metabolic tissues in an isozyme-specific manner. In this study, we examined the effects of a fructose-enriched diet on expressions of ACSL isoforms in the liver of hamsters. We showed that the fructose diet markedly reduced the mRNA and protein expressions of ACSL3 in hamster liver without significant effects on other ACSLs. The decrease in ACSL3 abundance was accompanied by a reduction in ACSL-catalyzed synthesis of arachidonyl-CoA and oleoyl-CoA in liver homogenates of hamsters fed the fructose diet as opposed to normal diet. We further showed that fructose diet specifically reduced expressions of three key components of the LXR signaling pathway, namely, liver X receptor (LXR)α, LXRβ, and retinoid X receptor (RXR)β. Exogenous expression and activation of LXRα/β increased hamster ACSL3 promoter activities in a LXR-responsive element (LXRE)-dependent fashion. Finally, we showed that treating hamsters with LXR agonist GW3965 increased hepatic ACSL3 expression without affecting other ACSL isoforms. Furthermore, the ligand-induced increases of ACSL3 expression were accompanied with the reduction of hepatic triglyceride levels in GW3965-treated hamster liver. Altogether, our studies demonstrate that fructose diet has a negative impact on LXR signaling pathway in liver tissue and reduction of ACSL3 expression/activity could be a causal factor for fructose-induced hepatic steatosis.

  10. High-fructose diet downregulates long-chain acyl-CoA synthetase 3 expression in liver of hamsters via impairing LXR/RXR signaling pathway[S

    Science.gov (United States)

    Dong, Bin; Kan, Chin Fung Kelvin; Singh, Amar B.; Liu, Jingwen

    2013-01-01

    Long-chain acyl-CoA synthetases (ACSL) play key roles in fatty acid metabolism in liver and other metabolic tissues in an isozyme-specific manner. In this study, we examined the effects of a fructose-enriched diet on expressions of ACSL isoforms in the liver of hamsters. We showed that the fructose diet markedly reduced the mRNA and protein expressions of ACSL3 in hamster liver without significant effects on other ACSLs. The decrease in ACSL3 abundance was accompanied by a reduction in ACSL-catalyzed synthesis of arachidonyl-CoA and oleoyl-CoA in liver homogenates of hamsters fed the fructose diet as opposed to normal diet. We further showed that fructose diet specifically reduced expressions of three key components of the LXR signaling pathway, namely, liver X receptor (LXR)α, LXRβ, and retinoid X receptor (RXR)β. Exogenous expression and activation of LXRα/β increased hamster ACSL3 promoter activities in a LXR-responsive element (LXRE)-dependent fashion. Finally, we showed that treating hamsters with LXR agonist GW3965 increased hepatic ACSL3 expression without affecting other ACSL isoforms. Furthermore, the ligand-induced increases of ACSL3 expression were accompanied with the reduction of hepatic triglyceride levels in GW3965-treated hamster liver. Altogether, our studies demonstrate that fructose diet has a negative impact on LXR signaling pathway in liver tissue and reduction of ACSL3 expression/activity could be a causal factor for fructose-induced hepatic steatosis. PMID:23427282

  11. High fructose consumption induces DNA methylation at PPARα and CPT1A promoter regions in the rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Koji [Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake (Japan); Munetsuna, Eiji [Department of Biochemistry, Fujita Health University School of Medicine, Toyoake (Japan); Yamada, Hiroya, E-mail: hyamada@fujita-hu.ac.jp [Department of Hygiene, Fujita Health University School of Medicine, Toyoake (Japan); Ando, Yoshitaka [Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University Hospital, Toyoake (Japan); Yamazaki, Mirai; Taromaru, Nao; Nagura, Ayuri; Ishikawa, Hiroaki [Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake (Japan); Suzuki, Koji [Department of Public Health, Fujita Health University School of Health Sciences, Toyoake (Japan); Teradaira, Ryoji [Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake (Japan); Hashimoto, Shuji [Department of Hygiene, Fujita Health University School of Medicine, Toyoake (Japan)

    2015-12-04

    DNA methylation status is affected by environmental factors, including nutrition. Fructose consumption is considered a risk factor for the conditions that make up metabolic syndrome such as dyslipidemia. However, the pathogenetic mechanism by which fructose consumption leads to metabolic syndrome is unclear. Based on observations that epigenetic modifications are closely related to induction of metabolic syndrome, we hypothesized that fructose-induced metabolic syndrome is caused by epigenetic alterations. Male SD rats were designated to receive water or 20% fructose solution for 14 weeks. mRNA levels for peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1A (CPT1A) was analyzed using Real-time PCR. Restriction digestion and real-time PCR (qAMP) was used for the analysis of DNA methylation status. Hepatic lipid accumulation was also observed by fructose intake. Fructose feeding also significantly decreased mRNA levels for PPARα and CPT1A. qAMP analysis demonstrated the hypermethylation of promoter regions of PPARα and CTP1A genes. Fructose-mediated attenuated gene expression may be mediated by alterations of DNA methylation status, and pathogenesis of metabolic syndrome induced by fructose relates to DNA methylation status. - Highlights: • No general consensus has been reached regarding the molecular mechanisms of the pathogenesis of fructose-induced diseases. • Significant increase in hepatic total methylation level was observed after fructose-supplemented feeding. • Fructose feeding significantly decreased mRNA levels for PPARα and CPT1A. • qAMP analysis demonstrated the hypermethylation of promoter regions of PPARα and CTP1A genes. • Fructose-mediated attenuated gene expression may be mediated by alterations of DNA methylation status in rat liver.

  12. High-intensity interval training has beneficial effects on cardiac remodeling through local renin-angiotensin system modulation in mice fed high-fat or high-fructose diets.

    Science.gov (United States)

    de Oliveira Sá, Guilherme; Dos Santos Neves, Vívian; de Oliveira Fraga, Shyrlei R; Souza-Mello, Vanessa; Barbosa-da-Silva, Sandra

    2017-11-15

    HIIT (high-intensity interval training) has the potential to reduce cardiometabolic risk factors, but the effects on cardiac remodeling and local RAS (renin-angiotensin system) in mice fed high-fat or high-fructose diets still need to be fully addressed. Sixty male C57BL/6 mice (12weeks old) were randomly divided into three groups, control (C), High-fat (HF), or High-fructose diet (HRU) and were monitored for eight weeks before being submitted to the HIIT. Each group was randomly assigned to 2 subgroups, one subgroup was started on a 12-week HIIT protocol (T=trained group), while the other subgroup remained non-exercised (NT=not-trained group). HIIT reduced BM and systolic blood pressure in high-fat groups, while enhanced insulin sensitivity after high-fat or high-fructose intake. Moreover, HIIT reduced left ventricular hypertrophy in HF-T and HFRU-T. Notably, HIIT modulated key factors in the local left ventricular renin-angiotensin-system (RAS): reduced protein expression of renin, ACE (Angiotensin-converting enzyme), and (Angiotensin type 2 receptor) AT2R in HF-T and HFRU-T groups but reduced (Angiotensin type 1 receptor) AT1R protein expression only in the high-fat trained group. HIIT modulated ACE2/Ang (1-7)/Mas receptor axis. ACE2 mRNA gene expression was enhanced in HF-T and HFRU-T groups, complying with elevated Mas (Mas proto-oncogene, G protein-coupled receptor) receptor mRNA gene expression after HIIT. This study shows the effectiveness of HIIT sessions in producing improvements in insulin sensitivity and mitigating LV hypertrophy, though hypertension was controlled only in the high-fat-fed submitted to HIIT protocol. Local RAS system in the heart mediates these findings and receptor MAS seems to play a pivotal role when it comes to the amelioration of cardiac structural and functional remodeling due to HIIT. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway.

    Science.gov (United States)

    Chen, H L; Tsai, T C; Tsai, Y C; Liao, J W; Yen, C C; Chen, C M

    2016-12-12

    In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides on high-fructose-induced hepatic steatosis and the possible molecular mechanism. An animal model of 30% high-fructose-induced NAFLD in C57BL/6J mice was established. The experiment is divided into the following six groups: (1) normal: H2O drinking water; (2) mock: H2O+30% fructose; (3) KL: low-dose kefir peptides (50 mg kg(-1))+30% fructose; (4) KM: medium-dose kefir peptides (100 mg kg(-1))+30% fructose; (5) KH: high-dose kefir peptides (150 mg kg(-1))+30% fructose; and (6) CFM: commercial fermented milk (100 mg kg(-1))+30% fructose. The results show that kefir peptides improve fatty liver syndrome by decreasing body weight, serum alanine aminotransferase, triglycerides, insulin and hepatic triglycerides, cholesterol, and free fatty acids as well as the inflammatory cytokines (TNF-α, IL-6 and IL-1β) that had been elevated in fructose-induced NAFLD mice. In addition, kefir peptides markedly increased phosphorylation of AMPK to downregulate its targeted enzymes, ACC (acetyl-CoA carboxylase) and SREBP-1c (sterol regulatory element-binding protein 1), and inhibited de novo lipogenesis. Furthermore, kefir peptides activated JAK2 to stimulate STAT3 phosphorylation, which can translocate to the nucleus, and upregulated several genes, including the CPT1 (carnitine palmitoyltransferase-1) involved in fatty acid oxidation. Our data have demonstrated that kefir peptides can improve the symptoms of NAFLD, including body weight, energy intake, inflammatory reaction and the formation

  14. Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

    Science.gov (United States)

    Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2013-12-01

    Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

  15. High-fructose diet downregulates long-chain acyl-CoA synthetase 3 expression in liver of hamsters via impairing LXR/RXR signaling pathway[S

    OpenAIRE

    Dong, Bin; Kan, Chin Fung Kelvin; Singh, Amar B.; Liu, Jingwen

    2013-01-01

    Long-chain acyl-CoA synthetases (ACSL) play key roles in fatty acid metabolism in liver and other metabolic tissues in an isozyme-specific manner. In this study, we examined the effects of a fructose-enriched diet on expressions of ACSL isoforms in the liver of hamsters. We showed that the fructose diet markedly reduced the mRNA and protein expressions of ACSL3 in hamster liver without significant effects on other ACSLs. The decrease in ACSL3 abundance was accompanied by a reduction in ACSL-c...

  16. High Fat, High Fructose, High Cholesterol Feeding Causes Severe NASH and Cecal Microbiota Dysbiosis in Juvenile Ossabaw Swine.

    Science.gov (United States)

    Panasevich, Matthew R; Meers, Grace M; Linden, Melissa A; Booth, Frank W; Perfield, James W; Fritsche, Kevin L; Wankhade, Umesh D; Chintapalli, Sree V; Shankar, Kartik; Ibdah, J A; Rector, R Scott

    2017-09-12

    Pediatric obesity and nonalcoholic steatohepatitis (NASH) are on the rise in industrialized countries, yet our ability to mechanistically examine this relationship is limited by the lack of a suitable higher animal model. Here, we examined the effects of high fat, high fructose corn syrup, high cholesterol Western style diet (WD)-induced obesity on NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine. Juvenile female Ossabaw swine (5 weeks old) were fed WD (43.0% fat; 17.8% high fructose corn syrup; 2% cholesterol) or low-fat diet (CON/lean; 10.5% fat) for 16 wks (n=6 each) or 36 wks (n=4 each). WD-fed pigs developed obesity, dyslipidemia, and systemic insulin resistance compared with CON pigs. In addition, obese WD-fed pigs developed severe NASH, with hepatic steatosis, hepatocyte ballooning, inflammatory cell infiltration, and fibrosis after 16 weeks, with further exacerbation of histological inflammation and fibrosis after 36 wks of WD-feeding. WD-feeding also resulted in robust cecal microbiota changes including increased relative abundances of families and genera in Proteobacteria (Phigh fat, high fructose, high cholesterol diet develop obesity and severe microbiota dysbiosis with a pro-inflammatory signature and a NASH phenotype directly relevant to the pediatric/adolescent and young adult population. Copyright © 2017, American Journal of Physiology-Endocrinology and Metabolism.

  17. Effect of high fructose administration on histopathology of kidney, heart and aorta of rats

    Directory of Open Access Journals (Sweden)

    Rasha Saleh

    2017-03-01

    Results: Nephropathy was achieved in fructose group after one month as indicated by biochemical assay. Pathological observation showed that high fructose administration decreased size of cardio-myocytes, increased cardiac interstitial fibrosis score and aortic wall thickness. In kidneys, high fructose administration decreased glomerular tuft area and corpuscular area, increased percentage in the rats affected with interstitial renal fibrosis score 1 and percentage of rats had glomerular sclerosis score 2. Conclusion: High fructose in diet should be avoided because it can damage kidney, heart and aorta in rats. [J Adv Vet Anim Res 2017; 4(1.000: 71-79

  18. Zataria multiflora increases insulin sensitivity and PPARγ gene expression in high fructose fed insulin resistant rats

    Directory of Open Access Journals (Sweden)

    Abbas Mohammadi

    2014-04-01

    Full Text Available   Objective(s:In insulin resistance, the insulin action in liver, muscles and adipocytes decreases and result in hyperglycemia, dyslipidemia and hyperinsulinemia. In this study we evaluate the effect of Zataria multiflora extract on insulin sensitivity in high fructose fed insulin resistant rats, since this extract was shown antihyperglycemic effect in streptozotocin induced diabetes in rats.   Materials and Methods:Experimental rats were fed with high fructose diet for 6 weeks and then were treated with Z. multiflora extractor a pioglitazone solution for 2 weeks. Blood and tissue samples were collected for analysis at the end of two weeks. Blood glucose, serum level of triglyceride and cholesterol were measured by auto analyzer. Insulin and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA method. Plasma free fatty acids profile was studied by gas chromatography.  Peroxisome proliferator activated receptor (PPAR.γ and Glucose transporter type 4 (GLUT.4 gene expressions were assessed by real time polymerase chain reaction (PCR and western blotting. Results: Animals were treated by Z. multiflora extractshowed insulin (43±11pmol/l, adiponectin (5.3±0.5 μg/ml, glucose (144±9.8 mg/dl, and triglyceride (120±10 mg/dl levels significantly improved as compare with the control group [insulin (137±34 pmol/l, adiponectin (3.9±0.15 μg/ml, glucose (187±15mg/dl, and triglycerides (217±18 mg/dl]. PPARγ protein level, also significantly increased in Zataria multiflora treated group. Conclusion: This study demonstrates the beneficial effects of Zataria multiflora extract on insulin resistance in rats fed with a high-fructose diet through at least three mechanisms including direct insulin like effect, increasing in adiponectin and of PPARγ protein expression.   

  19. Chromium regulation of multiple gene expression in rats with high-fructose diet-induced metabolic syndrome

    Science.gov (United States)

    Chromium (Cr) supplementation alleviates the metabolic syndrome, glucose intolerance, depression, excess body fat, and type 2 diabetes. However, not all studies have reported beneficial effects of Cr. Molecular evidence is lacking on the effects of Cr. The objective of this study was to investigate ...

  20. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    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

  1. High-Fructose Corn Syrup: What Are the Concerns?

    Science.gov (United States)

    ... Nutrition and healthy eating What is high-fructose corn syrup? What are the health concerns? Answers from Katherine Zeratsky, R.D., L.D. High-fructose corn syrup is a common sweetener in sodas and ...

  2. 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...

  3. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    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.

  4. 21 CFR 184.1866 - High fructose corn syrup.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true High fructose corn syrup. 184.1866 Section 184.1866... Listing of Specific Substances Affirmed as GRAS § 184.1866 High fructose corn syrup. (a) High fructose corn syrup, a sweet, nutritive saccharide mixture containing either approximately 42 or 55 percent...

  5. Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels

    DEFF Research Database (Denmark)

    Gradel, Anna Katrina Jógvansdóttir; Salomonsson, Max; Sørensen, Charlotte Mehlin

    2018-01-01

    received a diet containing normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat/Fruc) for 28 weeks from age 4-weeks. Measurements included body weight (BW), systolic blood pressure (SBP), m...

  6. Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice.

    Science.gov (United States)

    Priyadarshini, Emayavaramban; Anuradha, Carani Venkatraman

    2017-02-01

    High intake of dietary fructose causes perturbation in lipid metabolism and provokes lipid-induced insulin resistance. A rise in glucocorticoids (GCs) has recently been suggested to be involved in fructose-induced insulin resistance. The objective of the study was to investigate the effect of GC blockade on lipid abnormalities in insulin-resistant mice. Insulin resistance was induced in mice by administering a high-fructose diet (HFrD) for 60 days. Mifepristone (RU486), a GC antagonist, was administered to HFrD-fed mice for the last 18 days, and the intracellular and extracellular GC levels, the glucocorticoid receptor (GR) activation and the expression of GC-regulated genes involved in lipid metabolism were examined. HFrD elevated the intracellular GC content in both liver and adipose tissue and enhanced the GR nuclear translocation. The plasma GC level remained unchanged. The levels of free fatty acids and triglycerides in plasma were elevated, accompanied by increased plasma insulin and glucose levels and decreased hepatic glycogen content. Treatment with RU486 reduced plasma lipid levels, tissue GC levels and the expression of GC-targeted genes involved in lipid accumulation, and it improved insulin sensitivity. This study demonstrated that HFrD-induced lipid accumulation and insulin resistance are mediated by enhanced GC in liver and adipose tissue and that GC antagonism might reduce fructose-induced lipid abnormalities and insulin resistance. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  7. Abnormalities in carbohydrate and lipid metabolisms in high-fructose dietfed insulin-resistant rats: amelioration by Catharanthus roseus treatments.

    Science.gov (United States)

    Rasineni, Karuna; Bellamkonda, Ramesh; Singareddy, Sreenivasa Reddy; Desireddy, Saralakumari

    2013-09-01

    High intake of dietary fructose has been shown to exert a number of adverse metabolic effects in humans and experimental animals. The present study was proposed to elucidate the effect of Catharanthus roseus (C. roseus) leaf powder treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats of body weight around 180 g were divided into four groups, two of these groups (groups C and C+CR) were fed with standard pellet diet and the other two groups (groups F and F+CR) were fed with high-fructose (66 %) diet. C. roseus leaf powder suspension in water (100 mg/kg body weight/day) was administered orally to group C+CR and group F+CR. At the end of a 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. roseus treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F was significantly decreased with C. roseus treatment in group F+CR. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. roseus treatment in group F+CR. In conclusion, our study demonstrates that C. roseus treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose-induced alterations in carbohydrate and lipid metabolisms. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

  8. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent.

    Science.gov (United States)

    Tetri, Laura H; Basaranoglu, Metin; Brunt, Elizabeth M; Yerian, Lisa M; Neuschwander-Tetri, Brent A

    2008-11-01

    The aims of this study were to determine whether combining features of a western lifestyle in mice with trans fats in a high-fat diet, high-fructose corn syrup in the water, and interventions designed to promote sedentary behavior would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH). Male C57BL/6 mice fed ad libitum high-fat chow containing trans fats (partially hydrogenated vegetable oil) and relevant amounts of a high-fructose corn syrup (HFCS) equivalent for 1-16 wk were compared with mice fed standard chow or mice with trans fats or HFCS omitted. Cage racks were removed from western diet mice to promote sedentary behavior. By 16 wk, trans fat-fed mice became obese and developed severe hepatic steatosis with associated necroinflammatory changes. Plasma alanine aminotransferase levels increased, as did liver TNF-alpha and procollagen mRNA, indicating an inflammatory and profibrogenic response to injury. Glucose intolerance and impaired fasting glucose developed within 2 and 4 wk, respectively. Plasma insulin, resistin, and leptin levels increased in a profile similar to that seen in patients with NASH. The individual components of this diet contributed to the phenotype independently; isocaloric replacement of trans fats with lard established that trans fats played a major role in promoting hepatic steatosis and injury, whereas inclusion of HFCS promoted food consumption, obesity, and impaired insulin sensitivity. Combining risk factors for the metabolic syndrome by feeding mice trans fats and HFCS induced histological features of NASH in the context of a metabolic profile similar to patients with this disease. Because dietary trans fats promoted liver steatosis and injury, their role in the epidemic of NASH needs further evaluation.

  9. High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels.

    Science.gov (United States)

    Dong, Bin; Singh, Amar Bahadur; Azhar, Salman; Seidah, Nabil G; Liu, Jingwen

    2015-04-01

    High fructose diet (HFD) induces dyslipidemia and insulin resistance in experimental animals and humans with incomplete mechanistic understanding. By utilizing mice and hamsters as in vivo models, we investigated whether high fructose consumption affects serum PCSK9 and liver LDL receptor (LDLR) protein levels. Feeding mice with an HFD increased serum cholesterol and reduced serum PCSK9 levels as compared with the mice fed a normal chow diet (NCD). In contrast to the inverse relationship in mice, serum PCSK9 and cholesterol levels were co-elevated in HFD-fed hamsters. Liver tissue analysis revealed that PCSK9 mRNA and protein levels were both reduced in mice and hamsters by HFD feeding, however, liver LDLR protein levels were markedly reduced by HFD in hamsters but not in mice. We further showed that circulating PCSK9 clearance rates were significantly lower in hamsters fed an HFD as compared with the hamsters fed NCD, providing additional evidence for the reduced hepatic LDLR function by HFD consumption. The majority of PCSK9 in hamster serum was detected as a 53 kDa N-terminus cleaved protein. By conducting in vitro studies, we demonstrate that this 53 kDa truncated hamster PCSK9 is functionally active in promoting hepatic LDLR degradation. Our studies for the first time demonstrate that high fructose consumption increases serum PCSK9 concentrations and reduces liver LDLR protein levels in hyperlipidemic hamsters. The positive correlation between circulating cholesterol and PCSK9 and the reduction of liver LDLR protein in HFD-fed hamsters suggest that hamster is a better animal model than mouse to study the modulation of PCSK9/LDLR pathway by atherogenic diets. Published by Elsevier Ireland Ltd.

  10. High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels

    Science.gov (United States)

    Dong, Bin; Singh, Amar Bahadur; Azhar, Salman; Seidah, Nabil G.; Liu, Jingwen

    2015-01-01

    Background High fructose diet (HFD) induces dyslipidemia and insulin resistance in experimental animals and humans with incomplete mechanistic understanding. By utilizing mice and hamsters as in vivo models, we investigated whether high fructose consumption affects serum PCSK9 and liver LDL receptor (LDLR) protein levels. Results Feeding mice with a HFD increased serum cholesterol and reduced serum PCSK9 levels as compared with the mice fed a normal chow diet (NCD). In contrast to the inverse relationship in mice, serum PCSK9 and cholesterol levels were co-elevated in HFD-fed hamsters. Liver tissue analysis revealed that PCSK9 mRNA and protein levels were both reduced in mice and hamsters by HFD feeding, however, liver LDLR protein levels were markedly reduced by HFD in hamsters but not in mice. We further showed that circulating PCSK9 clearance rates were significantly lower in hamsters fed a HFD as compared with the hamsters fed NCD, providing additional evidence for the reduced hepatic LDLR function by HFD consumption. The majority of PCSK9 in hamster serum was detected as a 53 kDa N-terminus cleaved protein. By conducting in vitro studies, we demonstrate that this 53 kDa truncated hamster PCSK9 is functionally active in promoting hepatic LDLR degradation. Conclusion Our studies for the first time demonstrate that high fructose consumption increases serum PCSK9 concentrations and reduces liver LDLR protein levels in hyperlipidemic hamsters. The positive correlation between circulating cholesterol and PCSK9 and the reduction of liver LDLR protein in HFD-fed hamsters suggest that hamster is a better animal model than mouse to study the modulation of PCSK9/LDLR pathway by atherogenic diets. PMID:25682035

  11. High fat, high fructose, high cholesterol feeding causes severe NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine

    Science.gov (United States)

    Female Ossabaw swine (5 weeks old) were fed WD (43.0% fat; 17.8% high fructose corn syrup; 2% cholesterol) or low-fat diet (CON/lean; 10.5% fat) for 16 wks (n=6 each) or 36 wks (n=4 each). WD-fed pigs developed obesity, dyslipidemia, and systemic insulin resistance compared with CON pigs. In additio...

  12. Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats.

    Science.gov (United States)

    Ajiboye, Taofeek O; Raji, Hikmat O; Adeleye, Abdulwasiu O; Adigun, Nurudeen S; Giwa, Oluwayemisi B; Ojewuyi, Oluwayemisi B; Oladiji, Adenike T

    2016-03-30

    The effect of Hibiscus sabdariffa calyx extract was evaluated in high-fructose-induced metabolic syndrome rats. Insulin resistance, hyperglycemia, dyslipidemia and oxidative rout were induced in rats using high-fructose diet. High-fructose diet-fed rats were administered 100 and 200 mg kg(-1) body weight of H. sabdariffa extract for 3 weeks, starting from week 7 of high-fructose diet treatment. High-fructose diet significantly (P insulin, total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDLc) and very-low-density lipoprotein cholesterol (VLDLc), with a concomitant reduction in high-density lipoprotein cholesterol (HDLc). These alterations were significantly ameliorated by the extract. High-fructose diet-mediated decreases in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-red) and glucose 6-phosphate dehydrogenase (Glc 6-PD) were significantly (P insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in high-fructose-induced metabolic syndrome rats. © 2015 Society of Chemical Industry.

  13. Chia (salvia Hispanica L.) Enhances Hsp, Pgc-1 Alpha Expressions And Improves Glucose Tolerance In Diet-induced Obese Rats

    OpenAIRE

    Marineli; Rafaela da Silva; Moura; Carolina Soares; Moraes; Erica Aguiar; Lenquiste; Sabrina Alves; Barboza Lollo; Pablo Christiano; Morato; Priscila Neder; Amaya-Farfan; Jaime; Marostica; Mario Roberto; Jr.

    2016-01-01

    Objective: The aim of this study was to investigate the effects of chia seed and chia oil on heat shock protein (HSP) and related parameters in diet-induced obese rats. Methods: Animals were divided in six groups: control, high-fat and high-fructose diet (HFF), and HFF with chia seed or chia oil in short (6-wk) and long (12-wk) treatments. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and proteins controlling oxidative energy metab...

  14. Enzymatic production of high fructose syrup from Agave tequilana ...

    African Journals Online (AJOL)

    ... fructose-glucose ratio, agave syrup has lower viscosity and surface tension than the corn syrup. Due to its high content of fructans, the head of the A. tequilana Weber var. blue is a promising raw material for the industrial production of high fructose syrups. Key words: Syrup, fructose, fructans, Agave tequilana, inulin, ...

  15. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent

    OpenAIRE

    Tetri, Laura H.; Basaranoglu, Metin; Brunt, Elizabeth M.; Yerian, Lisa M.; Neuschwander-Tetri, Brent A.

    2008-01-01

    The aims of this study were to determine whether combining features of a western lifestyle in mice with trans fats in a high-fat diet, high-fructose corn syrup in the water, and interventions designed to promote sedentary behavior would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH). Male C57BL/6 mice fed ad libitum high-fat chow containing trans fats (partially hydrogenated vegetable oil) and relevant amounts of a high-fr...

  16. Restoration of autophagy alleviates hepatic ER stress and impaired insulin signalling transduction in high fructose-fed male mice.

    Science.gov (United States)

    Wang, Hao; Sun, Ruo-Qiong; Zeng, Xiao-Yi; Zhou, Xiu; Li, Songpei; Jo, Eunjung; Molero, Juan C; Ye, Ji-Ming

    2015-01-01

    High-carbohydrate (mainly fructose) consumption is a major dietary factor for hepatic insulin resistance, involving endoplasmic reticulum (ER) stress and lipid accumulation. Because autophagy has been implicated in ER stress, the present study investigated the role of autophagy in high-fructose (HFru) diet-induced hepatic ER stress and insulin resistance in male C57BL/6J mice. The results show that chronic HFru feeding induced glucose intolerance and impaired insulin signaling transduction in the liver, associated with ER stress and the accumulation of lipids. Intriguingly, hepatic autophagy was suppressed as a result of activation of mammalian target of rapamycin. The suppressed autophagy was detected within 6 hours after HFru feeding along with activation of both inositol-requiring enzyme 1 and protein kinase RNA-like endoplasmic reticulum kinase pathways. These events occurred prior to lipid accumulation or lipogenesis and were sufficient to blunt insulin signaling transduction with activation of c-Jun N-terminal kinase/inhibitory-κB kinase and serine phosphorylation of insulin receptor substrate 1. The stimulation of autophagy attenuated ER stress- and c-Jun N-terminal kinase/inhibitory-κB kinase-associated impairment in insulin signaling transduction in a mammalian target of rapamycin -independent manner. Taken together, our data suggest that restoration of autophagy functions disrupted by fructose is able to alleviate ER stress and improve insulin signaling transduction.

  17. Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats

    Directory of Open Access Journals (Sweden)

    Abbas Mohammadi

    2016-01-01

    Conclusion: This study demonstrates the beneficial effects of trigonella foenum-graecum extract on insulin resistance in rats fed on a high-fructose diet. At least three mechanisms are involved, including direct insulin-like effect, increase in adiponectin levels, and PPARγ protein expression.

  18. Cardiovascular effects of high-fructose intake in rats with nitric oxide deficiency

    Directory of Open Access Journals (Sweden)

    Zemančíková Anna

    2014-09-01

    Full Text Available The aim of this study was to evaluate the involvement of nitric oxide (NO system damage in the deleterious effects of high-fructose intake in rats. Fructose was administered as 10% solution in drinking water to twelve-week-old male Wistar rats for the period of 8 weeks. Blood pressure was measured by tail-cuff plethysmography. After sacrificing the rats at the end of the treatment, relative weights of heart and liver and biochemical parameters in blood plasma were determined. Reactivity of isolated conduit arteries was measured using a force-displacement transducer for recording isometric tension. Fructose drinking rats had increased blood pressure and impaired acetylcholine-induced relaxation of the thoracic aorta in comparison with control rats drinking just tap water. Relative liver weight and plasma concentrations of glucose and triglycerides were also elevated after fructose administration. In a further group of Wistar rats, inhibition of NO production by administration of NG-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg/day was performed throughout fructose intake. L-NAME treatment itself induces increase in blood pressure and relative heart weight as well as impairment in arterial relaxation and contractility. However, in these rats, fructose administration did not cause further elevation of blood pressure and other abnormalities observed in rats receiving fructose without L-NAME. Our results showed that in the state of NO deficiency (induced by L-NAME administration fructose does not induce cardiovascular and metabolic alterations which develop in rats with a functional NO system. This indicates that impairment of the NO system may participate in many of the adverse effects induced by high-fructose intake.

  19. Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Jegatheesan, Prasanthi; Beutheu, Stéphanie; Freese, Kim; Waligora-Dupriet, Anne-Judith; Nubret, Esther; Butel, Marie-Jo; Bergheim, Ina; De Bandt, Jean-Pascal

    2016-07-01

    A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague-Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (Pliver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level.

  20. Activation of PPARα ameliorates hepatic insulin resistance and steatosis in high fructose-fed mice despite increased endoplasmic reticulum stress.

    Science.gov (United States)

    Chan, Stanley M H; Sun, Ruo-Qiong; Zeng, Xiao-Yi; Choong, Zi-Heng; Wang, Hao; Watt, Matthew J; Ye, Ji-Ming

    2013-06-01

    Endoplasmic reticulum (ER) stress is suggested to cause hepatic insulin resistance by increasing de novo lipogenesis (DNL) and directly interfering with insulin signaling through the activation of the c-Jun N-terminal kinase (JNK) and IκB kinase (IKK) pathway. The current study interrogated these two proposed mechanisms in a mouse model of hepatic insulin resistance induced by a high fructose (HFru) diet with the treatment of fenofibrate (FB) 100 mg/kg/day, a peroxisome proliferator-activated receptor α (PPARα) agonist known to reduce lipid accumulation while maintaining elevated DNL in the liver. FB administration completely corrected HFru-induced glucose intolerance, hepatic steatosis, and the impaired hepatic insulin signaling (pAkt and pGSK3β). Of note, both the IRE1/XBP1 and PERK/eIF2α arms of unfolded protein response (UPR) signaling were activated. While retaining the elevated DNL (indicated by the upregulation of SREBP1c, ACC, FAS, and SCD1 and [3H]H2O incorporation into lipids), FB treatment markedly increased fatty acid oxidation (indicated by induction of ACOX1, p-ACC, β-HAD activity, and [14C]palmitate oxidation) and eliminated the accumulation of diacylglycerols (DAGs), which is known to have an impact on insulin signaling. Despite the marked activation of UPR signaling, neither JNK nor IKK appeared to be activated. These findings suggest that lipid accumulation (mainly DAGs), rather than the activation of JNK or IKK, is pivotal for ER stress to cause hepatic insulin resistance. Therefore, by reducing the accumulation of deleterious lipids, activation of PPARα can ameliorate hepatic insulin resistance against increased ER stress.

  1. The high-fat high-fructose hamster as an animal model for niacin's biological activities in humans.

    Science.gov (United States)

    Connolly, Beth A; O'Connell, Daniel P; Lamon-Fava, Stefania; LeBlanc, Daniel F; Kuang, Yu-Lin; Schaefer, Ernst J; Coppage, Andrew L; Benedict, Claude R; Kiritsy, Christopher P; Bachovchin, William W

    2013-12-01

    Niacin has been used for more than 50 years to treat dyslipidemia, yet the mechanisms underlying its lipid-modifying effects remain unknown, a situation stemming at least in part from a lack of validated animal models. The objective of this study was to determine if the dyslipidemic hamster could serve as such a model. Dyslipidemia was induced in Golden Syrian hamsters by feeding them a high-fat, high-cholesterol, and high-fructose (HF/HF) diet. The effect of high-dose niacin treatment for 18 days and 28 days on plasma lipid levels and gene expression was measured. Niacin treatment produced significant decreases in plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and free fatty acids (FFA), but had no measureable effect on high-density lipoprotein cholesterol (HDL-C) in the dyslipidemic hamster. Niacin treatment also produced significant increases in hepatic adenosine ATP-Binding Cassette A1 (ABCA1) mRNA, ABCA1 protein, apolipoprotein A-I (Apo A-I) mRNA, and adipose adiponectin mRNA in these animals. With the exception of HDL-C, the lipid effects of niacin treatment in the dyslipidemic hamster closely parallel those observed in humans. Moreover, the effects of niacin treatment on gene expression of hepatic proteins related to HDL metabolism are similar to those observed in human cells in culture. The HF/HF-fed hamster could therefore serve as an animal model for niacin's lowering of proatherogenic lipids and mechanisms of action relative to lipid metabolism. © 2013.

  2. Portal vein glucose entry triggers a coordinated cellular response that potentiates hepatic glucose uptake and storage in normal but not high-fat/high-fructose-fed dogs.

    Science.gov (United States)

    Coate, Katie C; Kraft, Guillaume; Irimia, Jose M; Smith, Marta S; Farmer, Ben; Neal, Doss W; Roach, Peter J; Shiota, Masakazu; Cherrington, Alan D

    2013-02-01

    The cellular events mediating the pleiotropic actions of portal vein glucose (PoG) delivery on hepatic glucose disposition have not been clearly defined. Likewise, the molecular defects associated with postprandial hyperglycemia and impaired hepatic glucose uptake (HGU) following consumption of a high-fat, high-fructose diet (HFFD) are unknown. Our goal was to identify hepatocellular changes elicited by hyperinsulinemia, hyperglycemia, and PoG signaling in normal chow-fed (CTR) and HFFD-fed dogs. In CTR dogs, we demonstrated that PoG infusion in the presence of hyperinsulinemia and hyperglycemia triggered an increase in the activity of hepatic glucokinase (GK) and glycogen synthase (GS), which occurred in association with further augmentation in HGU and glycogen synthesis (GSYN) in vivo. In contrast, 4 weeks of HFFD feeding markedly reduced GK protein content and impaired the activation of GS in association with diminished HGU and GSYN in vivo. Furthermore, the enzymatic changes associated with PoG sensing in chow-fed animals were abolished in HFFD-fed animals, consistent with loss of the stimulatory effects of PoG delivery. These data reveal new insight into the molecular physiology of the portal glucose signaling mechanism under normal conditions and to the pathophysiology of aberrant postprandial hepatic glucose disposition evident under a diet-induced glucose-intolerant condition.

  3. Developmental programming of the metabolic syndrome: Next-generation sequencing analysis of transcriptome expression in a rat model of maternal high fructose intake.

    Science.gov (United States)

    Chao, Yung-Mei; Tain, You-Lin; Leu, Steve; Wu, Kay L H; Lee, Wei-Chia; Chan, Julie Y H

    2016-10-25

    Excessive fructose intake is related to a high prevalence of metabolic syndrome, while little attention has been paid to the impact of maternal high-fructose (HF) intake on the development of metabolic syndrome and organ-specific transcriptome alterations in the offspring. We utilized RNA next-generation sequencing (NGS) technology to analyze the transcriptome expression in four organs (kidney, brain, heart, and urinary bladder) from 1-day, 3-week, and 3-month-old male offspring exposed to maternal HF diet. Maternal HF induced various phenotypes of metabolic syndrome in adult male offspring. We observed that maternal HF exposure induces long-term alterations of gene expression in the brain, heart, kidney, and urinary bladder in adult offspring. Different organs do not respond similarly to maternal HF intake. We found that changes in expression of Errfi1 and Ctgf were shared by four organs at 1 day of age. Also, a number of genes regulating fructose metabolism, glycolysis/gluconeogenesis, fatty acid metabolism, and insulin signalling appear to be regulated by maternal HF intake in different organs at 1 day of age. Our NGS results are of significance to the development of maternal interventions in the prevention of maternal HF-induced organ-specific programming, in order to reduce the global burden of metabolic syndrome.

  4. Emodin Prevents Intrahepatic Fat Accumulation, Inflammation and Redox Status Imbalance During Diet-Induced Hepatosteatosis in Rats

    Directory of Open Access Journals (Sweden)

    Valerio Nobili

    2012-02-01

    Full Text Available High-fat and/or high-carbohydrate diets may predispose to several metabolic disturbances including liver fatty infiltration (hepatosteatosis or be associated with necro-inflammation and fibrosis (steatohepatitis. Several studies have emphasized the hepatoprotective effect of some natural agents. In this study, we investigated the potential therapeutic effects of the treatment with emodin, an anthraquinone derivative with anti-oxidant and anti-cancer abilities, in rats developing diet-induced hepatosteatosis and steatohepatitis. Sprague-Dawley rats were fed a standard diet (SD for 15 weeks, or a high-fat/high-fructose diet (HFD/HF. After 5 weeks, emodin was added to the drinking water of some of the SD and HFD/HF rats. The experiment ended after an additional 10 weeks. Emodin-treated HFD/HF rats were protected from hepatosteatosis and metabolic derangements usually observed in HFD/HF animals. Furthermore, emodin exerted anti-inflammatory activity by inhibiting the HFD/HF-induced increase of tumor necrosis factor (TNF-α. Emodin also affected the hepatocytes glutathione homeostasis and levels of the HFD/HF-induced increase of glutathionylated/phosphorylated phosphatase and tensin homolog (PTEN. In conclusion, we demonstrated that a natural agent such as emodin can prevent hepatosteatosis, preserving liver from pro-inflammatory and pro-oxidant damage caused by HFD/HF diet. These findings are promising, proposing emodin as a possible hindrance to progression of hepatosteatosis into steatohepatitis.

  5. Dietary Omega-3 Fatty Acid Deficiency and High Fructose Intake in the Development of Metabolic Syndrome, Brain Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2013-07-01

    Full Text Available Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS. Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD, promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.

  6. Chia (Salvia hispanica L.) enhances HSP, PGC-1α expressions and improves glucose tolerance in diet-induced obese rats.

    Science.gov (United States)

    Marineli, Rafaela da Silva; Moura, Carolina Soares; Moraes, Érica Aguiar; Lenquiste, Sabrina Alves; Lollo, Pablo Christiano Barboza; Morato, Priscila Neder; Amaya-Farfan, Jaime; Maróstica, Mário Roberto

    2015-05-01

    The aim of this study was to investigate the effects of chia seed and chia oil on heat shock protein (HSP) and related parameters in diet-induced obese rats. Animals were divided in six groups: control, high-fat and high-fructose diet (HFF), and HFF with chia seed or chia oil in short (6-wk) and long (12-wk) treatments. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and proteins controlling oxidative energy metabolism were determined. The limit of significance was set at P chia seed or chia oil did not reduce body weight gain or abdominal fat accumulation. However, chia seed and chia oil in both treatments improved glucose and insulin tolerance. Chia oil in both treatments induced expression of HSP70 and HSP25 in skeletal muscle. Short treatment with chia seed increased expression of HSP70, but not HSP25. Chia oil in both treatments restored superoxide dismutase and glutathione peroxidase expression. Extended treatment with chia seed and short treatment with chia oil restored peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression. Chia oil restored the antioxidant system and induced the expression of a higher number of proteins than chia seed. The present study demonstrated new properties and molecular mechanisms associated with the beneficial effects of chia seed and chia oil consumption in diet-induced obese rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Antioxidant potential of dietary chia seed and oil (Salvia hispanica L.) in diet-induced obese rats.

    Science.gov (United States)

    Marineli, Rafaela da Silva; Lenquiste, Sabrina Alves; Moraes, Érica Aguiar; Maróstica, Mário Roberto

    2015-10-01

    This study aimed to investigate the effects of dietary chia seed and oil on plasma and liver oxidative status in diet-induced obese rats. Thirty-six Wistar rats were divided in six groups (6 animals each): control group was fed the American Institute of Nutrition (AIN)-93M diet; HFF group was fed a high-fat and high-fructose (HFF) diet; chia seed short (6-weeks) and long (12-weeks) treatments received an HFF diet with chia seed; chia oil short (6-weeks) and long (12-weeks) treatments received an HFF diet with chia oil. Plasma and hepatic biomarkers of lipid peroxidation, endogenous enzymatic and non-enzymatic antioxidant systems and antioxidant capacity were determined. HFF diet induced weight gain, oxidative stress and lipid peroxidation in plasma and liver of animals. Compared to HFF group chia seed and chia oil (12 and 6weeks) intake increased plasma reduced thiol (GSH) levels, plasma catalase (CAT) and glutathione peroxidase (GPx) activities. In the liver glutathione reductase (GRd) activity was enhanced, while CAT and GPx activities did not change. There were no differences in plasma and liver superoxide dismutase activity among chia diets and HFF group. Chia (seed and oil) intake did not modify liver lipid peroxidation, but was able to reduce plasma thiobarbituric acid reactive substances (TBARS) and 8-isoprostane levels increased by HFF group. Plasma and hepatic antioxidant capacity values were increased in chia seed and oil groups about 35% and 47%, respectively, compared to HFF group. Chia groups presented similar antioxidant potential, regardless of treatment time. Dietary chia seed and oil reduced oxidative stress in vivo, since it improved antioxidant status and reduced lipid peroxidation in diet-induced obese rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Differential modulation of cytosolic lipases activities in liver and adipose tissue by high-carbohydrate diets.

    Science.gov (United States)

    Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Mario, Érica Guilhen; de Souza Cordeiro, Letícia Maria; Avelar, Gleide Fernandes; Botion, Leida Maria; Chaves, Valéria Ernestânia

    2016-08-01

    Several studies have demonstrated that a high-fructose (FRUC) diet induces metabolic and haemodynamic abnormalities, known as the metabolic syndrome, which are characterised by obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. In this study, the effect of a FRUC diet (60 % fructose) for 8 weeks on the metabolism of lipids in liver and epididymal adipose tissue from Wistar rats was compared with the AIN-93M diet and the effects of the AIN-93M diet were compared with a chow diet. The FRUC diet induced marked increases in both hepatocyte lipid droplet volume and postprandial serum levels of triacylglycerol (TAG), but reduced the postprandial serum levels of insulin. The AIN-93M diet induced marked increases in the hepatocyte lipid droplet volume and the serum levels of insulin, without affecting the serum levels of TAG. We found that isocaloric substitution of cornstarch, dextrinised cornstarch and sucrose (AIN-93M diet) for fructose did not affect the hepatic VLDL-TAG secretion and adipose tissue glucose uptake, lipolysis and cytosolic lipases activities in rats. However, the high-fructose diet induced a severe steatosis in liver accompanied by a decrease in cytosolic lipases activities. In adipose tissue, the FRUC diet induced a decrease in the lipoprotein lipase activity, and an increase in lipogenesis. FRUC and AIN-93M diets induced changes in lipid homeostasis in liver and adipose tissue by distinct biochemical mechanisms.

  9. Central and Metabolic Effects of High Fructose Consumption: Evidence from Animal and Human Studies

    Directory of Open Access Journals (Sweden)

    Alexandra Stoianov

    2014-12-01

    Full Text Available Fructose consumption has increased dramatically in the last 40 years, and its role in the pathogenesis of the metabolic syndrome has been implicated by many studies. It is most often encountered in the diet as sucrose (glucose and fructose or high-fructose corn syrup (55% fructose. At high levels, dietary exposure to fructose triggers a series of metabolic changes originating in the liver, leading to hepatic steatosis, hypertriglyceridemia, insulin resistance, and decreased leptin sensitivity. Fructose has been identified to alter biological pathways in other tissues including the central nervous system (CNS, adipose tissue, and the gastrointestinal system. Unlike glucose, consumption of fructose produces smaller increases in the circulating satiety hormone glucagon-like peptide 1 (GLP-1, and does not attenuate levels of the appetite suppressing hormone ghrelin. In the brain, fructose contributes to increased food consumption by activating appetite and reward pathways, and stimulating hypothalamic AMPK activity, a nutrient-sensitive regulator of food intake. Recent studies investigating the neurophysiological factors linking fructose consumption and weight gain in humans have demonstrated differential activation of brain regions that govern appetite, motivation and reward processing. Compared to fructose, glucose ingestion produces a greater reduction of hypothalamic neuronal activity, and increases functional connectivity between the hypothalamus and other reward regions of the brain, indicating that these two sugars regulate feeding behavior through distinct neural circuits. This review article outlines the current findings in fructose-feeding studies in both human and animal models, and discusses the central effects on the CNS that may lead to increased appetite and food intake. Keywords: Fructose, Metabolic syndrome, Appetite, Central nervous system

  10. Effects of L-Carnitine on inducible nitric oxide synthase, insulin like ...

    African Journals Online (AJOL)

    Egyptian Journal of Biochemistry and Molecular Biology ... Metabolism of high dietary fructose induces insulin resistance and metabolic adaptation including changes in gene expression. The present ... Insulin-like Growth Factor-1(IGF-1), insulin receptor substrate-1 (IRS-1) in kidney tissues of rats fed on high fructose diet.

  11. Antioxidant effect of Azadirachta indica on high fat diet induced diabetic Charles Foster rats.

    Science.gov (United States)

    Shrivastava, Atul; Chaturvedi, Upma; Sonkar, Ravi; Khanna, Ashok Kumar; Saxena, J K; Bhatia, Gitika

    2012-05-01

    Oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Excessively high levels of free radicals cause damage to cellular proteins, membrane lipids and nucleic acids, and eventually cell death. The present study was designed to investigate the possible effect of Azadirachta indica leaf extract in high fat diet induced diabetic Charles Foster rats. The increased level of lipidperoxidation and altered levels of enzymatic (superoxide dismutase, glutathione peroxidase and catalase) and non-enzymatic (glutathione) antioxidants were seen in high fructose fed animals. The treatment with A. indica leaf extract significantly normalized the altered levels of lipid peroxidation and antioxidant status at 400 mg/kg b.w. dose. The A. indica leaf extract was also tested for in vitro inhibition of generation of superoxide anion and hydroxyl free radical in both enzymatic and non-enzymatic systems. The A. indica leaf extract was found to inhibit generation of superoxide anion and hydroxyl free radical significantly at 200 μg/ml concentration. Data of present study demonstrated that the A. indica leaf extract has both antidiabetic and antioxidant properties.

  12. Glycemic effect of nutritive sweeteners: Honey, sugar and high fructose corn syrup

    Science.gov (United States)

    Controversy currently exists over whether all nutritive sweeteners produce similar metabolic effects. Using a randomized, crossover design we evaluated the effects of chronic consumption of 3 nutritive sweeteners (honey, sucrose and high fructose corn syrup (HFCS)) on glucose tolerance in overweigh...

  13. High Fructose Corn Syrup, Mercury, and Autism--Is There a Link?

    Science.gov (United States)

    Opalinski, Heather A.

    2012-01-01

    The purpose of this article is to review relevant background literature and research regarding the evidence linking high fructose corn syrup (HFCS), mercury, and the increased incidence of autism among the population in the United States. Results of review suggest that rigorous scientific studies need to be performed to conclusively identify the…

  14. Effect of feeding grape pomace on selected metabolic parameters associated with high fructose feeding in growing Sprague-Dawley rats.

    Science.gov (United States)

    Khanal, Ramesh C; Howard, Luke R; Rogers, Theodore J; Wilkes, Samuel E; Dhakal, Ishwori B; Prior, Ronald L

    2011-12-01

    The effect of feeding grape pomace on certain metabolic parameters associated with high fructose (HF) feeding was studied. Forty male growing Sprague-Dawley rats were randomly assigned into groups: (1) control; (2) HF; (3) HF with low-level (1.5% of diet) grape pomace (HF+LP), and (4) HF with high-level (5.0% of diet) grape pomace (HF+HP). The HF+LP and HF+HP diets provided 115 and 218 mg of procyanidins/kg, respectively. Compared with the controls, HF-fed animals consumed less and were smaller, whereas animals in the HF+LP and HF+HP groups were in between. A similar trend was observed for abdominal fat and abdominal fat as a percentage of body weight. No change in heart or kidney weight occurred. Liver weight as a percentage of body weight was higher for animals when fructose was included in the diet compared with those on control diet, and inclusion of grape pomace had no effect. Fasting plasma glucose, insulin, and triglyceride levels tended to be higher in animals fed HF diet, and grape pomace reduced their levels to values similar to the control animals. Compared with control animals, HF-fed animals had higher weekly postprandial plasma triglycerides, which were reduced by feeding grape pomace, but no change in plasma cholesterol was observed. Glucose intolerance was observed in animals fed HF diet and was accompanied by a 25% increase in homeostatic model assessment (HOMA) of insulin resistance. Inclusion of grape pomace increased glucose tolerance and insulin sensitivity. No significant change (P>.1) in HOMA of β-cell function or Quantitative Insulin-Sensitivity Check Index was observed. Overall, HF diet did not produce as strong a response of metabolic syndrome as has been shown in the literature. The inclusion of grape pomace in the diet was effective in modulating some aspects of metabolic parameters associated with metabolic syndrome, and the higher level of grape pomace in the diet produced a slightly better response than the lower level.

  15. Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats.

    Science.gov (United States)

    Cioffi, Federica; Senese, Rosalba; Lasala, Pasquale; Ziello, Angela; Mazzoli, Arianna; Crescenzo, Raffaella; Liverini, Giovanna; Lanni, Antonia; Goglia, Fernando; Iossa, Susanna

    2017-03-24

    Evidence indicates that many forms of fructose-induced metabolic disturbance are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage; however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are events involved in metabolic disease resulting from a fructose-rich diet. In the present study, we evaluated the degree of oxidative damage to liver mtDNA and its repair, in addition to the state of oxidative stress and antioxidant defense in the liver of rats fed a high-fructose diet. We used male rats feeding on a high-fructose or control diet for eight weeks. Our results showed an increase in mtDNA damage in the liver of rats fed a high-fructose diet and this damage, as evaluated by the expression of DNA polymerase γ, was not repaired; in addition, the mtDNA copy number was found to be significantly reduced. A reduction in the mtDNA copy number is indicative of impaired mitochondrial biogenesis, as is the finding of a reduction in the expression of genes involved in mitochondrial biogenesis. In conclusion, a fructose-rich diet leads to mitochondrial and mtDNA damage, which consequently may have a role in liver dysfunction and metabolic diseases.

  16. Antioxidant Potential Of Dietary Chia Seed And Oil (salvia Hispanica L.) In Diet-induced Obese Rats

    OpenAIRE

    Marineli; Rafaela da Silva; Lenquiste; Sabrina Alves; Moraes; Erica Aguiar; Marostica; Mario Roberto; Jr.

    2016-01-01

    This study aimed to investigate the effects of dietary chia seed and oil on plasma and liver oxidative status in dietinduced obese rats. Thirty-six Wistar rats were divided in six groups (6 animals each): control group was fed the American Institute of Nutrition (AIN)-93 M diet; HFF group was fed a high-fat and high-fructose (HFF) diet; chia seed short (6-weeks) and long (12-weeks) treatments received an HFF diet with chia seed; chia oil short (6-weeks) and long (12-weeks) treatments received...

  17. Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet?

    Science.gov (United States)

    Seneff, Stephanie; Wainwright, Glyn; Mascitelli, Luca

    2011-02-01

    The metabolic syndrome (MetS) is manifested by a lipid triad which includes elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol, by central obesity (central adiposity), insulin resistance, glucose intolerance and elevated blood pressure, and it is associated with an increased risk of type 2 diabetes and coronary heart disease. We have developed a new hypothesis regarding MetS as a consequence of a high intake in carbohydrates and food with a high glycemic index, particularly fructose, and relatively low intake of cholesterol and saturated fat. We support our arguments through animal studies which have shown that exposure of the liver to increased quantities of fructose leads to rapid stimulation of lipogenesis and accumulation of triglycerides. The adipocytes store triglycerides in lipid droplets, leading to adipocyte hypertrophy. Adipocyte hypertrophy is associated with macrophage accumulation in adipose tissue. An important modulator of obesity-associated macrophage responses in white adipose tissue is the death of adipocytes. Excess exposure to fructose intake determines the liver to metabolize high doses of fructose, producing increased levels of fructose end products, like glyceraldehyde and dihydroxyacetone phosphate, that can converge with the glycolytic pathway. Fructose also leads to increased levels of advanced glycation end products. The macrophages exposed to advanced glycation end products become dysfunctional and, on entry into the artery wall, contribute to plaque formation and thrombosis.

  18. Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats

    Directory of Open Access Journals (Sweden)

    Aburrahman Gun

    2016-01-01

    Full Text Available Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS. HFCS (6 weeks, 30% fed with drinking water caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

  19. Diet induced thermogenesis measured over 24h in a respiration chamber: effect of diet composition.

    NARCIS (Netherlands)

    Westerterp, K.R.; Wilson, S.A.; Rolland, V.

    1999-01-01

    Department of Human Biology, Maastricht University, The Netherlands. OBJECTIVE: To study the effect of diet composition on diet-induced thermogenesis (DIT) over 24h in a respiration chamber. SUBJECTS: Eight healthy female volunteers (age 27 +/- 3 y; body mass index, BMI 23 +/- 3 kg/m2). DIETS: A

  20. Effects of combined dietary chromium(III) propionate complex and thiamine supplementation on insulin sensitivity, blood biochemical indices, and mineral levels in high-fructose-fed rats.

    Science.gov (United States)

    Król, Ewelina; Krejpcio, Zbigniew; Michalak, Sławomir; Wójciak, Rafał W; Bogdański, Paweł

    2012-12-01

    Insulin resistance is the first step in glucose intolerance and the development of type 2 diabetes mellitus, thus effective prevention strategies should also include dietary interventions to enhance insulin sensitivity. Nutrients, such as microelement chromium(III) and thiamine, play regulatory roles in carbohydrate metabolism. The objective of this study was to evaluate the insulin-sensitizing potential of the combined supplementary chromium(III) propionate complex (CrProp) and thiamine in insulin resistance animal model (rats fed a high-fructose diet). The experiment was carried out on 40 nine-week-old male Wistar rats divided into five groups (eight animals each). Animals were fed ad libitum: the control diet (AIN-93 M) and high-fructose diets with and without a combination of two levels of CrProp (0.1 and 1 mg Cr/kg body mass/day) and two levels of thiamine (0.5 and 10 mg/kg body mass/day) for 8 weeks. At the end of the experiment rats were sacrificed to collect blood and internal organs for analyses of blood biochemical and hematologic indices as well as tissular microelement levels that were measured using appropriate methods. It was found that both supplementary CrProp and thiamine (given alone) have significant insulin-sensitizing and moderate blood-lipid-lowering properties, while the combined supplementation with these agents does not give synergistic effects in insulin-resistant rats. CrProp given separately increased kidney Cu and Cr levels, while thiamine alone increased hepatic Cu contents and decreased renal Zn and Cu contents.

  1. High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels.

    Science.gov (United States)

    Yu, Zhiping; Lowndes, Joshua; Rippe, James

    2013-12-01

    Intake of high-fructose corn syrup (HFCS) has been suggested to contribute to the increased prevalence of obesity, whereas a number of studies and organizations have reported metabolic equivalence between HFCS and sucrose. We hypothesized that HFCS and sucrose would have similar effects on energy-regulating hormones and metabolic substrates at normal levels of human consumption and that these values would not change over a 10-week, free-living period at these consumption levels. This was a randomized, prospective, double-blind, parallel group study in which 138 adult men and women consumed 10 weeks of low-fat milk sweetened with either HFCS or sucrose at levels of the 25th, 50th, and 90th percentile population consumption of fructose (the equivalent of 40, 90, or 150 g of sugar per day in a 2000-kcal diet). Before and after the 10-week intervention, 24-hour blood samples were collected. The area under the curve (AUC) for glucose, insulin, leptin, active ghrelin, triglyceride, and uric acid was measured. There were no group differences at baseline or posttesting for all outcomes (interaction, P > .05). The AUC response of glucose, active ghrelin, and uric acid did not change between baseline and posttesting (P > .05), whereas the AUC response of insulin (P < .05), leptin (P < .001), and triglyceride (P < .01) increased over the course of the intervention when the 6 groups were averaged. We conclude that there are no differences in the metabolic effects of HFCS and sucrose when compared at low, medium, and high levels of consumption. © 2013 Elsevier Inc. All rights reserved.

  2. Antiobesity effects of kimchi in diet-induced obese mice

    OpenAIRE

    Meizi Cui; Hee-Young Kim; Kyung Hee Lee; Ji-Kang Jeong; Ji-Hee Hwang; Kyu-Young Yeo; Byung-Hee Ryu; Jung-Ho Choi; Kun-Young Park

    2015-01-01

    Background: The present study was investigated to confirm the antiobesity effect of kimchi in high-fat diet-induced obese C57BL/6 mice. Methods: Mice in the high-fat diet (HFD) group, standardized kimchi (S-Kimchi) group, and Korean commercial kimchi (D-Kimchi) group, but not in the normal-diet group, were fed a high-fat diet (HFD) for the first 4 weeks to induce obesity. From the 5th to 8th weeks, the S- and D-Kimchi groups were fed an HFD containing 10% of S-Kimchi or D-Kimchi, respectiv...

  3. Intestinal scavenger receptor class B type I as a novel regulator of chylomicron production in healthy and diet-induced obese states.

    Science.gov (United States)

    Lino, Marsel; Farr, Sarah; Baker, Chris; Fuller, Mark; Trigatti, Bernardo; Adeli, Khosrow

    2015-09-01

    The small intestine contributes to diabetic dyslipidemia through the overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles. An important regulator of chylomicron generation is dietary lipid absorption, underlining the potential involvement of intestinal lipid transporters for developing dyslipidemia. Intestinal expression of scavenger receptor class B type I (SR-BI) has been found to be upregulated in animal models of insulin resistance. Here we characterized the potential importance of SR-BI in contributing to chylomicron production and postprandial hypertriglyceridemia in vivo. Postprandial triglyceride (TG)-rich lipoprotein (TRL) production was characterized in hamsters treated with the SR-BI inhibitor to block lipid transport-1 (BLT-1) under healthy conditions or conditions of diet-induced obesity and dyslipidemia. BLT-1 (1 mg/kg) or vehicle was administered acutely in chow-fed hamsters or gavaged twice daily over 10 days during high-fructose, high-fat, high-cholesterol (FFC) feeding. Effects of acute SR-BI inhibition by BLT-1 were confirmed in healthy fat-loaded rats. Finally, plasma lipid levels were compared between SR-BI(-/-) mice and their wild-type counterparts fed either chow or a 12-wk high-fat diet. Acute BLT-1 treatment reduced postprandial plasma and TRL TG levels in healthy hamsters and rats. Chronic BLT-1 treatment of FFC-fed hamsters blunted diet-induced weight gain and fasting hypertriglyceridemia, and lowered postprandial TRL-TG, -cholesterol, and -apoB48 levels. Finally, SR-BI(-/-) mice displayed lower plasma and TRL TG levels relative to wild type, and diet-induced weight gain and postprandial hypertriglyceridemia were hindered in SR-BI(-/-) mice. We conclude that intestinal SR-BI is a critical regulator of postprandial lipoprotein production, emphasizing its potential as a target for preventing diabetic dyslipidemia. Copyright © 2015 the American Physiological Society.

  4. Diet-Induced Ketosis Improves Cognitive Performance in Aged Rats

    Science.gov (United States)

    Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O.; Tsipis, Constantinos P.; Puchowicz, Michelle A.; LaManna, Joseph C.

    2010-01-01

    Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1α levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions. PMID:20204773

  5. Sugar or high fructose corn syrup-what should nurses teach patients and families?

    Science.gov (United States)

    Sobel, Linda L; Dalby, Elizabeth

    2014-04-01

    There is lack of consensus in the lay literature to support consumption of table sugar as a preferred sweetener when compared to high fructose corn syrup (HFCS). The purpose of this study was to search the literature for evidence to determine the health effects of consumption of table sugar (sucrose) and HFCS on blood glucose, lipid levels, obesity, and appetite as well as to make recommendations for patient and family teaching of those at risk for developing negative health outcomes, including coronary heart disease. Nursing and health-related databases, including CINAHL, PubMed, Cochrane Central Registry of Controlled Trials, and Health and Wellness were searched for research articles, which were compared and evaluated for purpose, sample size, procedure, findings, and level of evidence. Five studies that met inclusion criteria were evaluated. No difference was found in changes in blood glucose levels, lipid levels, or appetite between table sugar consumption and HFCS consumption. When only fructose was consumed, lipid levels were significantly increased. The evidence suggests that fructose, found in both table sugar and HFCS, has a negative effect on health outcomes. Clinicians should teach patients and families that all sugar consumption should be closely monitored and kept below the 40 g/day recommended by the World Health Organization. © 2014 Sigma Theta Tau International.

  6. A critical examination of the evidence relating high fructose corn syrup and weight gain.

    Science.gov (United States)

    Forshee, Richard A; Storey, Maureen L; Allison, David B; Glinsmann, Walter H; Hein, Gayle L; Lineback, David R; Miller, Sanford A; Nicklas, Theresa A; Weaver, Gary A; White, John S

    2007-01-01

    The use of high fructose corn syrup (HFCS) has increased over the past several decades in the United States while overweight and obesity rates have risen dramatically. Some scientists hypothesize that HFCS consumption has uniquely contributed to the increasing mean body mass index (BMI) of the U.S. population. The Center for Food, Nutrition, and Agriculture Policy convened an expert panel to discuss the published scientific literature examining the relationship between consumption of HFCS or "soft drinks" (proxy for HFCS) and weight gain. The authors conducted original analysis to address certain gaps in the literature. Evidence from ecological studies linking HFCS consumption with rising BMI rates is unreliable. Evidence from epidemiologic studies and randomized controlled trials is inconclusive. Studies analyzing the differences between HFCS and sucrose consumption and their contributions to weight gain do not exist. HFCS and sucrose have similar monosaccharide compositions and sweetness values. The fructose:glucose (F:G) ratio in the U.S. food supply has not appreciably changed since the introduction of HFCS in the 1960s. It is unclear why HFCS would affect satiety or absorption and metabolism of fructose any differently than would sucrose. Based on the currently available evidence, the expert panel concluded that HFCS does not appear to contribute to overweight and obesity any differently than do other energy sources. Research recommendations were made to improve our understanding of the association of HFCS and weight gain.

  7. Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4.

    Science.gov (United States)

    Wu, Kay L H; Wu, Chih-Wei; Tain, You-Lin; Huang, Li-Tung; Chao, Yung-Mei; Hung, Chun-Ying; Wu, Jin-Cheng; Chen, Siang-Ru; Tsai, Pei-Chia; Chan, Julie Y H

    2016-04-01

    Impairment of learning and memory has been documented in the later life of offspring to maternal consumption with high energy diet. Environmental stimulation enhances the ability of learning and memory. However, potential effects of environmental stimulation on the programming-associated deficit of learning and memory have not been addressed. Here, we examined the effects of enriched-housing on hippocampal learning and memory in adult female offspring rats from mother fed with 60% high fructose diet (HFD) during pregnancy and lactation. Impairment of spatial learning and memory performance in HFD group was observed in offspring at 3-month-old. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased in the offspring. Moreover, the HFD group showed an up-regulation of histone deacetylase 4 (HDAC4) in the nuclear fractions of hippocampal neurons. Stimulation to the offspring for 4weeks after winning with an enriched-housing environment effectively rescued the decrease in cognitive function and hippocampal BDNF level; alongside a reversal of the increased distribution of nuclear HDAC4. Together these results suggest that later life environmental stimulation effectively rescues the impairment of hippocampal learning and memory in female offspring to maternal HFD intake through redistributing nuclear HDAC4 to increase BDNF expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The Effect of Normally Consumed Amounts of Sucrose or High Fructose Corn Syrup on Lipid Profiles, Body Composition and Related Parameters in Overweight/Obese Subjects

    Directory of Open Access Journals (Sweden)

    Joshua Lowndes

    2014-03-01

    Full Text Available The American Heart Association (AHA has advocated that women and men not consume more than 100 and 150 kcal/day, respectively, from added sugars. These levels are currently exceeded by over 90% of the adult population in the United States. Few data exist on longer-term metabolic effects when sucrose and High Fructose Corn Syrup (HFCS, the principal sources of added dietary sugars, are consumed at levels typical of the general population. Sixty five overweight and obese individuals were placed on a eucaloric (weight stable diet for 10-weeks, which incorporated sucrose- or HFCS-sweetened, low-fat milk at 10% or 20% of calories in a randomized, double-blinded study. All groups responded similarly (interaction p > 0.05. There was no change in body weight in any of the groups over the 10-week study, or in systolic or diastolic blood pressure. Likewise, there were no changes in total cholesterol, triglycerides, low-density lipoprotein (LDL, or apolipoprotein B (Apo B. We conclude that (1 when consumed as part of a eucaloric diet fructose—when given with glucose (as normally consumed does not promote weight gain or an atherogenic lipid profile even when consumed at two to four times the level recently recommended by the AHA. (2 There were no differences between HFCS and sucrose on these parameters.

  9. Resveratrol protects rabbits against cholesterol diet- induced ...

    African Journals Online (AJOL)

    The excessive consumption of high cholesterol diet has been associated with an increased incidence of lipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim of these experiments was to investigate the protective effect of resveratrol co-administered with ...

  10. 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.

  11. Milk diets influence doxorubicin-induced intestinal toxicity in piglets

    DEFF Research Database (Denmark)

    Shen, R. L.; Pontoppidan, P. E.; Rathe, M.

    2016-01-01

    Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated...... IL-8 levels compared with DOX-Form (all P diet. Thus a single dose of DOX induces intestinal toxicity in preweaned pigs...... and may lead to a systemic inflammatory response. The toxicity is affected by type of enteral nutrition with more pronounced GI toxicity when formula is fed compared with bovine colostrum. The results indicate that bovine colostrum may be a beneficial supplementary diet for children subjected...

  12. The Kv1.3 channel blocker Vm24 enhances muscle glucose transporter 4 mobilization but does not reduce body-weight gain in diet-induced obese male rats.

    Science.gov (United States)

    Jaimes-Hoy, Lorraine; Gurrola, Georgina B; Cisneros, Miguel; Joseph-Bravo, Patricia; Possani, Lourival D; Charli, Jean-Louis

    2017-07-15

    Voltage-gated potassium channels 1.3 (Kv1.3) can be targeted to reduce diet-induced obesity and insulin resistance in mice. Since species-specific differences in Kv1.3 expression and pharmacology have been observed, we tested the effect of Vm24, a high-affinity specific blocker of Kv1.3 channels from Vaejovis mexicanus smithi, on body weight (BW), glucose tolerance and insulin resistance in diet-induced obese rats. Young adult male Wistar rats were switched to a high-fat/high-fructose (HFF) diet. Eighteen days later animals were divided in two groups: vehicle and Vm24 group. Subcutaneous injections were applied every other day until sacrifice 2months later. An additional cohort was maintained on standard chow. The HFF diet promoted obesity. Treatment with Vm24 did not alter various metabolic parameters such as food intake, BW gain, visceral white adipose tissue mass, adipocyte diameter, serum glucose, leptin and thyroid hormone concentrations, brown adipose tissue mass or uncoupling protein-1 expression, and insulin tolerance. Vm24 did reduce basal and glucose-stimulated serum insulin concentrations, serum C-peptide concentration, increased QUICKI, and tended to lower HOMA-IR. Vm24 treatment did not change the activation of insulin receptor substrate-1, but enhanced protein-kinase B activation and membrane glucose-transporter 4 (GLUT4) protein levels in skeletal muscle. In conclusion, in male rats, long-term blockade of Kv1.3 channels with Vm24 does not reduce weight gain and visceral adiposity induced by HFF diet; instead, it reduces serum insulin concentration, and enhances GLUT4 mobilization in skeletal muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Ginger-supplemented diet ameliorates ammonium nitrate-induced ...

    African Journals Online (AJOL)

    The present study was designed to evaluate the capacity of ginger to repair the oxidative stress induced by ammonium nitrate. 50 male rats were divided into 5 groups; they underwent an oral treatment of ammonium nitrate and/or ginger (N mg/kg body weight + G% in diet) during 30 days. Group I served as control (C); ...

  14. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced ...

    African Journals Online (AJOL)

    olayemitoyin

    lipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim of these experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet induced hyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= ...

  15. Intestinal Barrier Function and the Gut Microbiome Are Differentially Affected in Mice Fed a Western-Style Diet or Drinking Water Supplemented with Fructose.

    Science.gov (United States)

    Volynets, Valentina; Louis, Sandrine; Pretz, Dominik; Lang, Lisa; Ostaff, Maureen J; Wehkamp, Jan; Bischoff, Stephan C

    2017-05-01

    Background: The consumption of a Western-style diet (WSD) and high fructose intake are risk factors for metabolic diseases. The underlying mechanisms are largely unclear. Objective: To unravel the mechanisms by which a WSD and fructose promote metabolic disease, we investigated their effects on the gut microbiome and barrier function. Methods: Adult female C57BL/6J mice were fed a sugar- and fat-rich WSD or control diet (CD) for 12 wk and given access to tap water or fructose-supplemented water. The microbiota was analyzed with the use of 16S rRNA gene sequencing. Barrier function was studied with the use of permeability tests, and endotoxin, mucus thickness, and gene expressions were measured. Results: The WSD increased body weight gain but not endotoxin translocation compared with the CD. In contrast, high fructose intake increased endotoxin translocation 2.6- and 3.8-fold in the groups fed the CD + fructose and WSD + fructose, respectively, compared with the CD group. The WSD + fructose treatment also induced a loss of mucus thickness in the colon (-46%) and reduced defensin expression in the ileum and colon. The lactulose:mannitol ratio in the WSD + fructose mice was 1.8-fold higher than in the CD mice. Microbiota analysis revealed that fructose, but not the WSD, increased the Firmicutes:Bacteroidetes ratio by 88% for CD + fructose and 63% for WSD + fructose compared with the CD group. Bifidobacterium abundance was greater in the WSD mice than in the CD mice (63-fold) and in the WSD + fructose mice than in the CD + fructose mice (330-fold). Conclusions: The consumption of a WSD or high fructose intake differentially affects gut permeability and the microbiome. Whether these differences are related to the distinct clinical outcomes, whereby the WSD primarily promotes weight gain and high fructose intake causes barrier dysfunction, needs to be investigated in future studies. © 2017 American Society for Nutrition.

  16. 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

    The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model......, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization...... including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia...

  17. Paternal allele influences high fat diet-induced obesity.

    Science.gov (United States)

    Morita, Sumiyo; Horii, Takuro; Kimura, Mika; Arai, Yuji; Kamei, Yasutomi; Ogawa, Yoshihiro; Hatada, Izuho

    2014-01-01

    C57BL/6J (B6) mice are susceptible to high-fat diet (HFD)-induced obesity and have been used in metabolism research for many decades. However, the genetic component of HFD-induced obesity has not yet been elucidated. This study reports evidence for a paternal transmission of HFD-induced obesity and a correlated expression of Igf2 and Peg3 (paternal expressed gene 3) imprinted genes. We found that PWK mice are resistant to HFD-induced obesity compared to C57BL/6J mice. Therefore, we generated and analyzed reciprocal crosses between these mice, namely; (PWK×B6) F1 progeny with B6 father and (B6×PWK) F1 progeny with PWK father. The (PWK×B6) F1 mice were more sensitive to diet-induced obesity compared to (B6×PWK) F1 mice, suggesting a paternal transmission of diet-induced obesity. Expression analysis of imprinted genes in adipocytes revealed that HFD influences the expression of some of the imprinted genes in adipose tissue in B6 and PWK mice. Interestingly, Igf2 and Peg3, which are paternally expressed imprinted genes involved in the regulation of body fat accumulation, were down-regulated in B6 and (PWK×B6) F1 mice, which are susceptible to HFD-induced obesity, but not in PWK and (B6×PWK) F1 mice, which are resistant. Furthermore, in vitro analysis showed that Igf2, but not Peg3, had an anti-inflammatory effect on TNF-α induced MCP-1 expression in adipocytes. Taken together, our findings suggest that the down-regulation of Igf2 and Peg3 imprinted genes in adipocytes may be involved in the paternal transmission of HFD-induced obesity.

  18. Fructose diet alleviates acetaminophen-induced hepatotoxicity in mice.

    Directory of Open Access Journals (Sweden)

    Sungjoon Cho

    Full Text Available Acetaminophen (APAP is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v fructose in water (or regular water for 8 weeks, followed by oral administration of APAP. APAP-induced liver injury (determined by serum levels of liver enzymes was decreased by two-fold in mice pretreated with fructose. Fructose-treated mice exhibited (~1.5 fold higher basal glutathione levels and (~2 fold lower basal (mRNA and activity levels of Cyp1a2 and Cyp2e1, suggesting decreased bioactivation of APAP and increased detoxification of toxic metabolite in fructose-fed mice. Hepatic mRNA expression of heat shock protein 70 was also found increased in fructose-fed mice. Analysis of bacterial 16S rRNA gene amplicons from the cecal samples of vehicle groups showed that the fructose diet altered gut bacterial community, leading to increased α-diversity. The abundance of several bacterial taxa including the genus Anaerostipes was found to be significantly correlated with the levels of hepatic Cyp2e1, Cyp1a2 mRNA, and glutathione. Together, these results suggest that the fructose-supplemented diet decreases APAP-induced liver injury in mice, in part by reducing metabolic activation of APAP and inducing detoxification of toxic metabolites, potentially through altered composition of gut microbiota.

  19. High Fat Diet Induced Obesity and Nutrient Sensing TOR Signaling

    OpenAIRE

    Oldham, Sean

    2011-01-01

    Obesity has grown to epidemic proportions globally, with 400 million considered obese. Evidence indicates that excessive dietary accumulation of lipids (obesity) is a risk factor in causing deleterious effects on metabolism and has been strongly linked to the progression of heart disease and Type 2 diabetes. Investigating the origin and effects of high fat diet (HFD)-induced obesity and its genetic mediators is an important step in understanding the mechanisms that contribute to obesity. Howe...

  20. Inhibition of sphingolipid synthesis improves dyslipidemia in the diet-induced hamster model of insulin resistance: evidence for the role of sphingosine and sphinganine in hepatic VLDL-apoB100 overproduction.

    Science.gov (United States)

    Dekker, Mark J; Baker, Chris; Naples, Mark; Samsoondar, Josh; Zhang, Rianna; Qiu, Wei; Sacco, Jennifer; Adeli, Khosrow

    2013-05-01

    Sphingolipids have emerged as important bioactive lipid species involved in the pathogenesis of type 2 diabetes and cardiovascular disease. However, little is known of the regulatory role of sphingolipids in dyslipidemia of insulin-resistant states. We employed hamster models of dyslipidemia and insulin resistance to investigate the role of sphingolipids in hepatic VLDL overproduction, induction of insulin resistance, and inflammation. Hamsters were fed either a control chow diet, a high fructose diet, or a diet high in fat, fructose and cholesterol (FFC diet). They were then treated for 2 weeks with vehicle or 0.3 mg/kg myriocin, a potent inhibitor of de novo sphingolipid synthesis. Both fructose and FFC feeding induced significant increases in hepatic sphinganine, which was normalized to chow-fed levels with myriocin (P hamsters, regardless of diet. Myriocin treatment also led to improved insulin sensitivity and reduced hepatic SREBP-1c mRNA, though it did not appear to ameliorate the activation of hepatic inflammatory pathways. Importantly, direct treatment of primary hamster hepatocytes ex vivo with C2 ceramide or sphingosine led to an increased secretion of newly synthesized apoB100. Taken together, these data suggest that a) hepatic VLDL-apoB100 overproduction may be stimulated by ceramides and sphingosine and b) inhibition of sphingolipid synthesis can reduce circulating VLDL in hamsters and improve circulating lipids--an effect that is possibly due to improved insulin signaling and reduced lipogenesis but is independent of changes in inflammation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Glucose Transporter-8 (GLUT8) Mediates Glucose Intolerance and Dyslipidemia in High-Fructose Diet-Fed Male Mice

    OpenAIRE

    DeBosch, Brian J.; Chen, Zhouji; Brian N. Finck; Chi, Maggie; Moley, Kelle H.

    2013-01-01

    Members of the glucose transporter (GLUT) family of membrane-spanning hexose transporters are subjects of intensive investigation for their potential as modifiable targets to treat or prevent obesity, metabolic syndrome, and type 2 diabetes mellitus. Mounting evidence suggests that the ubiquitously expressed class III dual-specificity glucose and fructose transporter, GLUT8, has important metabolic homeostatic functions. We therefore tested the hypothesis that GLUT8 mediates the deleterious m...

  2. Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice.

    Science.gov (United States)

    Choi, Seung Hee; Leem, Jaechan; Park, Sungmi; Lee, Chong-Kee; Park, Keun-Gyu; Lee, In-Kyu

    2017-02-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks. Gemigliptin treatment attenuated WD-induced body mass gain, hypercholesterolemia, adipocyte hypertrophy, and macrophage infiltration into adipose tissue, which were accompanied by an increased expression of uncoupling protein 1 in subcutaneous fat. These events contributed to improved insulin sensitivity, as assessed by the homeostasis model assessment of insulin resistance and intraperitoneal insulin tolerance test. Furthermore, gemigliptin reduced WD-induced hepatic triglyceride accumulation via inhibition of de novo lipogenesis and activation of fatty acid oxidation, which was accompanied by AMP-dependent protein kinase activation. Gemigliptin ameliorated WD-induced hepatic inflammation and fibrosis through suppression of oxidative stress. These results suggest that DPP-4 inhibitors may represent promising therapeutic agents for metabolic syndrome beyond their current role as antihyperglycemic agents.

  3. Obesity-inducing diet promotes acylation stimulating protein resistance.

    Science.gov (United States)

    Fisette, Alexandre; Lapointe, Marc; Cianflone, Katherine

    2013-08-02

    Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system that is involved in energy homeostasis and inflammation. ASP acts on and correlates positively with postprandial fat clearance in healthy subjects. However, in obesity, ASP levels are elevated and correlate inversely with fat clearance, indicative of a potential resistance to ASP. Using a mouse model, we hypothesized that, over time, diet-induced obesity (DIO) would result in development of ASP insensitivity, as compared to chow-fed animals as controls. Injection of recombinant ASP in DIO mice failed to accelerate fat clearance to the same extent as in chow-fed mice. DIO mice exhibited higher basal levels of plasma ASP and, after 30weeks of diet, showed lower ASP receptor (C5L2) expression in adipose tissue compared to chow-fed mice. Additionally, ex vivo ASP stimulation failed to induce normal Ser(473)AKT phosphorylation in adipose tissue from DIO mice VS chow-fed controls. These results demonstrate for the first time a state of diet-induced ASP resistance. Changes in the ASP-C5L2 pathway dynamics in obesity could alter the development of obesity and co-morbidities such as atherosclerosis and type 2 diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Diet-induced dyslipidemia impairs reverse cholesterol transport in hamsters.

    Science.gov (United States)

    Tréguier, Morgan; Briand, François; Boubacar, Adamou; André, Agnès; Magot, Thierry; Nguyen, Patrick; Krempf, Michel; Sulpice, Thierry; Ouguerram, Khadija

    2011-09-01

    Reverse cholesterol transport (RCT) is an anti-atherogenic process by which cholesterol is effluxed from peripheral tissues by high-density lipoprotein (HDL) and returned to the liver for excretion into the bile and faeces. Dyslipidemia is thought to impair RCT through higher triglyceride-rich lipoprotein (TRL), low HDL-cholesterol and higher activity of cholesteryl ester transfer protein (CETP), which transfers cholesteryl esters from HDL to TRL for further hepatic uptake. As CETP pathway would represent a major route in human RCT, we therefore investigated whether diet-induced dyslipidemia impairs RCT in hamster, a CETP-expressing species. Golden Syrian hamsters were fed a chow or chow+0·3% cholesterol diet over 4 weeks. Biochemical parameters and in vivo VLDL-triglycerides secretion (Triton WR-1339 injection) were then measured. In vitro macrophage cholesterol efflux was measured, and in vivo macrophage-to-faeces RCT was also assessed after an intraperitoneal injection of (3) H-cholesterol-labelled hamster primary macrophages. Cholesterol-enriched diet increased plasma total cholesterol (144%), triglycerides (101%), VLDL-triglycerides secretion (175%), CETP activity (44%) and reduced HDL-cholesterol/total cholesterol ratio by 20% (P diet significantly increased hepatic total cholesterol and triglycerides by 459 and 118% and increased aortic total cholesterol content by 304%. In vitro cholesterol efflux from macrophages to plasma was significantly reduced by 25% with plasma from cholesterol-fed hamsters. In vivo RCT experiments showed a significant 75% reduction of macrophage-derived cholesterol faecal excretion in cholesterol-fed hamsters. Overall, these data demonstrate that diet-induced dyslipidemia severely impairs in vivo RCT in hamsters. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

  5. Effect of Substitution of Sugar by High Fructose Corn Syrup on the Physicochemical Properties of Bakery and Dairy Products: A Review

    Directory of Open Access Journals (Sweden)

    Azizollaah Zargaraan

    2016-10-01

    Full Text Available High fructose corn syrup (HFCS is commonly found in soft drinks and juice beverages, as well as in many pre-packaged foods such as breakfast cereals, baked goods and dairy desserts. Historically, sucrose (table sugar was primarily added to processed foods and beverages as the sweetening agent. In recent years, the use of HFCS has significantly increased in popularity due to its sweetness, ability to enhance flavor and shelf life, and its low cost. HFCF made by enzymatic isomerization of glucose to fructose was introduced as HFCS-42 (42% fructose and HFCS-55 (55% fructose and opened a new frontier for the sweetener and soft drink industries. Using a glucose isomerase, the starch in corn can be efficiently converted into glucose and then to various amounts of fructose. Hydrolysis of sucrose produces a 50:50 molar mixture of fructose and glucose. The primary difference is that these monosaccharides exist free in solution in HFCS, but in sucrose bonded together. The disaccharide sucrose is easily cleaved in the small intestine, so free fructose and glucose are absorbed from both sucrose and HFCS. The advantage to food manufacturers is that the free monosaccharide in HFCS provides better flavor enhancement, stability, freshness, texture, color, pourability, and consistency in foods in comparison to sucrose. The development of these inexpensive, sweet corn-based syrups made it profitable to replace sucrose (sugar and simple sugars with HFCS in our diet. In the present study, the replacement of sucrose with HFCS and its effect on the functionality and organoleptic properties of different food products were reviewed.

  6. High-fat diet induces apoptosis of hypothalamic neurons.

    Directory of Open Access Journals (Sweden)

    Juliana C Moraes

    Full Text Available Consumption of dietary fats is amongst the most important environmental factors leading to obesity. In rodents, the consumption of fat-rich diets blunts leptin and insulin anorexigenic signaling in the hypothalamus by a mechanism dependent on the in situ activation of inflammation. Since inflammatory signal transduction can lead to the activation of apoptotic signaling pathways, we evaluated the effect of high-fat feeding on the induction of apoptosis of hypothalamic cells. Here, we show that consumption of dietary fats induce apoptosis of neurons and a reduction of synaptic inputs in the arcuate nucleus and lateral hypothalamus. This effect is dependent upon diet composition, and not on caloric intake, since pair-feeding is not sufficient to reduce the expression of apoptotic markers. The presence of an intact TLR4 receptor, protects cells from further apoptotic signals. In diet-induced inflammation of the hypothalamus, TLR4 exerts a dual function, on one side activating pro-inflammatory pathways that play a central role in the development of resistance to leptin and insulin, and on the other side restraining further damage by controlling the apoptotic activity.

  7. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    Science.gov (United States)

    Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

    2013-12-01

    Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

  8. Diet-induced metabolic syndrome model in rats

    Directory of Open Access Journals (Sweden)

    Reza Homayounfar

    2013-03-01

    Full Text Available Background & Objective: Risk for heart disease, diabetes, and stroke increases with the number of the metabolic risk factors. In general, a person who has the metabolic syndrome is twice as likely to develop heart disease and five times as likely to develop diabetes as someone who does not have the metabolic syndrome. High-calorie-diet rodent models have contributed significantly to the analysis of the pathophysiology of the metabolic syndrome, but their phenotype varies distinctly between different studies and maybe is not very similar to a model of the metabolic syndrome in humans. We sought to create a model in this study close to the disease in humans.   Materials & Methods: Twenty male, Wistar rats were randomly assigned to the high-calorie diet group with 416 calories per 100 grams (researcher made or the control diet group for 12 weeks. Weight changes, lipid profile, glucose, insulin levels, and QUICKI index (an indicator of insulin sensitivity were measured. Weight changes were compared using the repeated measures and the independent t-test, and serum factors were compared using the independent t-test.   Results: There was a significant change in weight, glucose, insulin, and lipid profile except for HDL at the end of the study. The QUICKI index (0.34 ± 0.02 vs. 0.40 ± 0.01; p value <0.0001 suggested that insulin resistance had been created in the high-calorie diet group.   Conclusion: The present study demonstrates the ability to make diet-induced metabolic syndrome domestically.

  9. Change in postprandial substrate oxidation after a high fructose meal is related to Body Mass Index (BMI) in Healthy Men

    Science.gov (United States)

    Smeraglio, Anne C.; Kennedy, Emily K.; Horgan, Angela; Purnell, Jonathan Q.; Gillingham, Melanie B.

    2013-01-01

    Oral fructose decreases fat oxidation and increases carbohydrate (CHO) oxidation in obese subjects, but the metabolic response to fructose in lean individuals is less well understood. The purpose of this study was to assess the effects of a single fructose-rich mixed meal on substrate oxidation in young healthy non-obese males. We hypothesized that a decrease in fat oxidation and an increase in carbohydrate oxidation would be observed following a fructose-rich mixed meal compared to a glucose-rich mixed meal. Twelve healthy males, normal to overweight and age 23–31 years old, participated in a double-blind, cross-over study. Each participant completed two study visits, eating a mixed meal containing 30% of the calories from either fructose or glucose. Blood samples for glucose, insulin, triglycerides, and leptin as well as gas exchange by indirect calorimetry were measured intermittently for 7 hours. Serum insulin was higher after a fructose mixed meal but plasma glucose, plasma leptin and serum triglycerides were not different. Mean postprandial respiratory quotient and estimated fat oxidation did not differ between the fructose and glucose meals. The change in fat oxidation between the fructose and glucose rich meals negatively correlated with BMI (r=−0.59, P=0.04 and r=−0.59, P=0.04 at the 4 and 7 hour time points, respectively). In healthy non-obese males, BMI correlates with altered postprandial fat oxidation after a high-fructose mixed meal. The metabolic response to a high fructose meal may be modulated by BMI. PMID:23746558

  10. Nutraceutical Potential of Tetracarpidium conophorum and Buccholzia coriacea in Diet-induced Hyperlipidemia

    OpenAIRE

    Eucharia Oluchi Nwaichi; Justice Obinna Osuoha; Michael Okechukwu Monanu

    2017-01-01

    The nutraceutical potential of Tetracarpidium conophorum and Buccholzia coriacea in diet-induced hyperlipidemia in male Wistar rats were investigated at the Plant Science and Biotechnology department, University of Port Harcourt, Nigeria in 2016. Diet-induced type II A hyperlipidemia in rat model was achieved by oral administration of egg yolk and groundnut oil formulations for 2 wk. Rats fed with normal diet and diet formulations constituted the negative control and test control in that orde...

  11. Suppression of Growth Rate of Colony-Associated Fungi by High Fructose Corn Syrup Feeding Supplement, Formic Acid, and Oxalic Acid

    Science.gov (United States)

    Select colony-associated fungi (bee isolates). Absidia sp., Ascosphaera apis, Aspergillus flavus, Fusarium sp., Penicillium glabrum, Mucor sp., showed a 40% reduction in radial growth rate with formic acid, a 28% reduction with oxalic acid, and a 15% reduction with fructose and high fructose corn sy...

  12. High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels.

    Science.gov (United States)

    Bocarsly, Miriam E; Powell, Elyse S; Avena, Nicole M; Hoebel, Bartley G

    2010-11-01

    High-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Some studies have shown that short-term access to HFCS can cause increased body weight, but the findings are mixed. The current study examined both short- and long-term effects of HFCS on body weight, body fat, and circulating triglycerides. In Experiment 1, male Sprague-Dawley rats were maintained for short term (8 weeks) on (1) 12 h/day of 8% HFCS, (2) 12 h/day 10% sucrose, (3) 24 h/day HFCS, all with ad libitum rodent chow, or (4) ad libitum chow alone. Rats with 12-h access to HFCS gained significantly more body weight than animals given equal access to 10% sucrose, even though they consumed the same number of total calories, but fewer calories from HFCS than sucrose. In Experiment 2, the long-term effects of HFCS on body weight and obesogenic parameters, as well as gender differences, were explored. Over the course of 6 or 7 months, both male and female rats with access to HFCS gained significantly more body weight than control groups. This increase in body weight with HFCS was accompanied by an increase in adipose fat, notably in the abdominal region, and elevated circulating triglyceride levels. Translated to humans, these results suggest that excessive consumption of HFCS may contribute to the incidence of obesity. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).

    Science.gov (United States)

    Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

    2013-11-01

    Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans.

  14. Addiction-like Synaptic Impairments in Diet-Induced Obesity.

    Science.gov (United States)

    Brown, Robyn Mary; Kupchik, Yonatan Michael; Spencer, Sade; Garcia-Keller, Constanza; Spanswick, David C; Lawrence, Andrew John; Simonds, Stephanie Elise; Schwartz, Danielle Joy; Jordan, Kelsey Ann; Jhou, Thomas Clayton; Kalivas, Peter William

    2017-05-01

    There is increasing evidence that the pathological overeating underlying some forms of obesity is compulsive in nature and therefore contains elements of an addictive disorder. However, direct physiological evidence linking obesity to synaptic plasticity akin to that occurring in addiction is lacking. We sought to establish whether the propensity to diet-induced obesity (DIO) is associated with addictive-like behavior, as well as synaptic impairments in the nucleus accumbens core considered hallmarks of addiction. Sprague Dawley rats were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions using fixed ratio 1, 3, and 5 and progressive ratio schedules. Subsequently, nucleus accumbens brain slices were prepared, and we tested for changes in the ratio between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate currents and the ability to exhibit long-term depression. We found that propensity to develop DIO is linked to deficits in the ability to induce long-term depression in the nucleus accumbens, as well as increased potentiation at these synapses as measured by AMPA/N-methyl-D-aspartate currents. Consistent with these impairments, we observed addictive-like behavior in DIO-prone rats, including 1) heightened motivation for palatable food; 2) excessive intake; and 3) increased food seeking when food was unavailable. Our results show overlap between the propensity for DIO and the synaptic changes associated with facets of addictive behavior, supporting partial coincident neurological underpinnings for compulsive overeating and drug addiction. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

  15. Hypolipidemic Activity of Spinacia Oleracea L. in Atherogenic Diet Induced Hyperlipidemic Rats.

    OpenAIRE

    Ranjan Kumar Giri

    2012-01-01

    Spinacia oleracea (spinach) of family Amaranthaceae is an important plant used traditionally for medicinal purposes. Hyperlipidemia was induced by treated orally with atherogenic diet. In atherogenic diet induced hyperlipidemic model, the rats receiving Spinacia oleracea powder showed significant reduction in total cholesterol, triglycerides, total protein and elevation of high density lipoprotein cholesterol. Spinacia oleracea was found to possess significant hypolipidemic activity. The resu...

  16. A review of the effects of glutamine-enriched diets on experimentally induced enterocolitis.

    Science.gov (United States)

    Rombeau, J L

    1990-01-01

    Studies in animal models of enterocolitis have failed to confirm the purported metabolic and functional benefits of bowel rest induced by use of an elemental diet. Recent reports have demonstrated that glutamine-supplemented diets ameliorate or reverse many of the adverse effects of experimentally induced enterocolitis. Human studies are needed to confirm these findings.

  17. Diet-induced metabolic hamster model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Bhathena, Jasmine; Kulamarva, Arun; Martoni, Christopher; Urbanska, Aleksandra Malgorzata; Malhotra, Meenakshi; Paul, Arghya; Prakash, Satya

    2011-01-01

    Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology. Experiments were planned to develop a diet-induced Bio F(1)B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O. In this study, we established a diet-induced Bio F(1)B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed with a high-fat/high cholesterol diet, as compared to animals fed with the control diet. Our study established that hamsters fed with a high-fat/high-cholesterol diet developed fatty liver and mild diabetes. Bio F(1)B hamsters fed with a high-fat/high-cholesterol diet may thus be a good animal model for research on the treatment of diet-induced metabolic syndrome complicated by

  18. Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice.

    NARCIS (Netherlands)

    Vroegrijk, I.O.; Diepen, J.A. van; Berg, S.; Westbroek, I.; Keizer, H.; Gambelli, L.; Hontecillas, R.; Bassaganya-Riera, J.; Zondag, G.C.; Romijn, J.A.; Havekes, L.M.; Voshol, P.J.

    2011-01-01

    BACKGROUND: Pomegranate seed oil has been shown to protect against diet induced obesity and insulin resistance. OBJECTIVE: To characterize the metabolic effects of punicic acid on high fat diet induced obesity and insulin resistance. DESIGN: High-fat diet or high-fat diet with 1% Pomegranate seed

  19. Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice

    Science.gov (United States)

    Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

  20. Daily exercise prevents diastolic dysfunction and oxidative stress in a female mouse model of western diet induced obesity by maintaining cardiac heme oxygenase-1 levels.

    Science.gov (United States)

    Bostick, Brian; Aroor, Annayya R; Habibi, Javad; Durante, William; Ma, Lixin; DeMarco, Vincent G; Garro, Mona; Hayden, Melvin R; Booth, Frank W; Sowers, James R

    2017-01-01

    Obesity is a global epidemic with profound cardiovascular disease (CVD) complications. Obese women are particularly vulnerable to CVD, suffering higher rates of CVD compared to non-obese females. Diastolic dysfunction is the earliest manifestation of CVD in obese women but remains poorly understood with no evidence-based therapies. We have shown early diastolic dysfunction in obesity is associated with oxidative stress and myocardial fibrosis. Recent evidence suggests exercise may increase levels of the antioxidant heme oxygenase-1 (HO-1). Accordingly, we hypothesized that diastolic dysfunction in female mice consuming a western diet (WD) could be prevented by daily volitional exercise with reductions in oxidative stress, myocardial fibrosis and maintenance of myocardial HO-1 levels. Four-week-old female C57BL/6J mice were fed a high-fat/high-fructose WD for 16weeks (N=8) alongside control diet fed mice (N=8). A separate cohort of WD fed females was allowed a running wheel for the entire study (N=7). Cardiac function was assessed at 20weeks by high-resolution cardiac magnetic resonance imaging (MRI). Functional assessment was followed by immunohistochemistry, transmission electron microscopy (TEM) and Western blotting to identify pathologic mechanisms and assess HO-1 protein levels. There was no significant body weight decrease in exercising mice, normalized body weight 14.3g/mm, compared to sedentary mice, normalized body weight 13.6g/mm (p=0.38). Total body fat was also unchanged in exercising, fat mass of 6.6g, compared to sedentary mice, fat mass 7.4g (p=0.55). Exercise prevented diastolic dysfunction with a significant reduction in left ventricular relaxation time to 23.8ms for exercising group compared to 33.0ms in sedentary group (pstress and myocardial fibrosis with improved mitochondrial architecture. HO-1 protein levels were increased in the hearts of exercising mice compared to sedentary WD fed females. This study provides seminal evidence that exercise

  1. Increased hepatic de novo lipogenesis and mitochondrial efficiency in a model of obesity induced by diets rich in fructose.

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Falcone, Italia; Coppola, Paola; Liverini, Giovanna; Iossa, Susanna

    2013-03-01

    To assess hepatic de novo lipogenesis and mitochondrial energetics as well as whole-body energy homeostasis in sedentary rats fed a fructose-rich diet. Male rats of 90 days of age were fed a high-fructose or control diet for 8 weeks. Body composition, energy balance, oxygen consumption, carbon dioxide production, non-protein respiratory quotient, de novo lipogenesis and insulin resistance were measured. Determination of specific activity of hepatic enzymes of de novo lipogenesis, mitochondrial mass, oxidative capacity and degree of coupling, together with parameters of oxidative stress and antioxidant defence, was also carried out. Body energy and lipid content as well as plasma insulin and non-esterified fatty acids were significantly higher in fructose-fed than in control rats. Significantly higher rates of net de novo lipogenesis and activities of hepatic lipogenic enzymes fatty acid synthase and stearoyl CoA desaturase-1 were found in fructose-fed rats compared to controls. Mitochondrial protein mass and degree of coupling were significantly higher in fructose-fed rats compared to controls. Hepatic mitochondria showed oxidative damage, both in the lipid and in the protein component, together with decreased activity of antioxidant defence. Liver mitochondrial compartment is highly affected by fructose feeding. The increased mitochondrial efficiency allows liver cells to burn less substrates to produce ATP for de novo lipogenesis and gluconeogenesis. In addition, increased lipogenesis gives rise to whole body and ectopic lipid deposition, and higher mitochondrial coupling causes mitochondrial oxidative stress.

  2. Postweaning low-calcium diet promotes later-life obesity induced by a high-fat diet.

    Science.gov (United States)

    He, Yong-Han; Li, Song-Tao; Wang, Yan-Yan; Wang, Guan; He, Ying; Liao, Xi-Lu; Sun, Chang-Hao; Li, Ying

    2012-10-01

    The aim of this study was to investigate the effects of a postweaning low-calcium diet on later obesity and explore the underlying mechanisms. Ninety-six male rats were weaned at 3 weeks of age, fed standard (STD: 0.50% calcium, n=48) and low-calcium (LC: 0.15% calcium, n=48) diets for 3 weeks, and then fed the standard diet for a 3-week washout period successively. Finally, the STD rats were divided into STD control and high-fat diet (HFD) groups, and the LC ones into LC control and LC+HFD (LCHF) groups. The STD and LC rats were fed the standard diet, while the HFD control and LCFD ones were fed a high-fat diet for 6 weeks to induce obesity. During the three feeding periods, adenosine-monophosphate-activated protein kinase (AMPK) and its responsive proteins phospho-acetyl-coA carboxylase, carnitine palmitoyltransferase 1 and uncoupling protein 3 were persistently down-regulated in the LC group (decreased by 18%, 24%, 18% and 20%, respectively) versus the STD group, and these effects were significantly more pronounced in the LCHFD group (decreased by 21%, 30%, 23% and 25%, respectively) than the HFD group by a later high-fat stimuli, causing more fat and body weight in adulthood. However, lipolysis enzymes, serum leptin, insulin and lipids were not significantly affected until the body weight and fat content changed at 15 weeks of age. The results suggest that the low-calcium diet after weaning promotes rat adult-onset obesity induced by high-fat diet, which might be achieved by programming expressions of genes involved in AMPK pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats.

    Science.gov (United States)

    Hsu, Ted M; Konanur, Vaibhav R; Taing, Lilly; Usui, Ryan; Kayser, Brandon D; Goran, Michael I; Kanoski, Scott E

    2015-02-01

    Excessive consumption of added sugars negatively impacts metabolic systems; however, effects on cognitive function are poorly understood. Also unknown is whether negative outcomes associated with consumption of different sugars are exacerbated during critical periods of development (e.g., adolescence). Here we examined the effects of sucrose and high fructose corn syrup-55 (HFCS-55) intake during adolescence or adulthood on cognitive and metabolic outcomes. Adolescent or adult male rats were given 30-day access to chow, water, and either (1) 11% sucrose solution, (2) 11% HFCS-55 solution, or (3) an extra bottle of water (control). In adolescent rats, HFCS-55 intake impaired hippocampal-dependent spatial learning and memory in a Barne's maze, with moderate learning impairment also observed for the sucrose group. The learning and memory impairment is unlikely based on nonspecific behavioral effects as adolescent HFCS-55 consumption did not impact anxiety in the zero maze or performance in a non-spatial response learning task using the same mildly aversive stimuli as the Barne's maze. Protein expression of pro-inflammatory cytokines (interleukin 6, interleukin 1β) was increased in the dorsal hippocampus for the adolescent HFCS-55 group relative to controls with no significant effect in the sucrose group, whereas liver interleukin 1β and plasma insulin levels were elevated for both adolescent-exposed sugar groups. In contrast, intake of HFCS-55 or sucrose in adults did not impact spatial learning, glucose tolerance, anxiety, or neuroinflammatory markers. These data show that consumption of added sugars, particularly HFCS-55, negatively impacts hippocampal function, metabolic outcomes, and neuroinflammation when consumed in excess during the adolescent period of development. © 2014 Wiley Periodicals, Inc.

  4. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis 1 2 3 4

    OpenAIRE

    Chung, Mei; Ma, Jiantao; Patel, Kamal; Berger, Samantha; Lau, Joseph; Lichtenstein, Alice H

    2014-01-01

    Background: Concerns have been raised about the concurrent temporal trend between simple sugar intakes, especially of fructose or high-fructose corn syrup (HFCS), and rates of nonalcoholic fatty liver disease (NAFLD) in the United States. Objective: We examined the effect of different amounts and forms of dietary fructose on the incidence or prevalence of NAFLD and indexes of liver health in humans. Design: We conducted a systematic review of English-language, human studies of any design in c...

  5. Effects of exercise and diet change on cognition function and synaptic plasticity in high fat diet induced obese rats

    National Research Council Canada - National Science Library

    Woo, Jinhee; Shin, Ki Ok; Park, So Young; Jang, Ki Soeng; Kang, Sunghwun

    2013-01-01

    .... This study was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced obesity in connection to the effects of regular exercise and dietary control for 8 weeks on the synaptic plasticity and cognitive abilities of brain...

  6. Dietary Egg Yolk Supplementation Improves Low-Protein-Diet-Induced Fatty Liver in Rats.

    Science.gov (United States)

    Erami, Kazuo; Tanaka, Yasutake; Kawamura, Sayaka; Miyago, Motonori; Sawazaki, Ai; Imaizumi, Katsumi; Sato, Masao

    2016-01-01

    Egg yolk is an important source of nutrients and contains different bioactive substances. In the present study, we studied the benefits of egg yolk in preventing low-protein-diet-induced fatty liver in rats. Rats were fed the following diets, which were based on the AIN-76 formula, for 2 wk: an adequate-protein diet containing 20% casein (C), a low-protein diet containing 5% casein (LP-C), a low-protein diet supplemented with 12.5% egg yolk (LP-EY), and a low-protein diet supplemented with 4.1% egg yolk oil (LP-EYO). The low-protein diets were adjusted to contain 4.13% protein and 4.7% lipids. The LP-C diet resulted in a greater increase in the liver trigriceride (TG) and the vacuolation and a greater decrease in the serum TG and free fatty acid (FFA) than did the C diet. These deviations in the serum and liver TG, serum FFA levels and the liver histopathology were corrected in rats fed the LP-EY diet but not in those fed the LP-EYO diet. Compared to rats fed the LP-C diet, although the activities of lipogenesis-related enzymes (fatty acid synthase, glucose-6-phosphate dehydrogenase, and malic enzyme) decreased in rats fed both of the LP-EY and LP-EYO diets, the level of the microsomal TG transfer protein (MTP) increased only in rats fed the LP-EY diet. Collectively, these results suggest that dietary egg yolk supplementation decreases the LP diet-induced accumulation of TG in the liver by increasing transport of TG in the liver, and egg yolk oil alone is not sufficient enough to bring about these benefits.

  7. Handling and diet-induced atherosclerosis in rabbits.

    Science.gov (United States)

    Jezierski, T; Mekking, P; Wiepkema, P R

    1993-07-01

    Atherosclerosis was induced in rabbits by feeding them a 2% cholesterol diet (CHOL) during a 5-week period. Twelve rabbits were fed with increasing amounts of CHOL food until the ad libitum level was reached, whereas in 24 other rabbits the food was limited to the amount eaten by the lowest consumer of the group to reduce individual variability in total amount of food consumed. Twice a day, half of the rabbits were handled carefully, the other half had normal laboratory practice contact with their caretaker. Feed intake and amount of atherosclerosis were determined for all experimental animals, while for the handled animals behavioural parameters and changes were recorded daily and per animal. On average the handled and non-handled rabbits took the same amount of food per week, although there were large individual differences. The handled animals showed some behavioural adaptation to being handled. Handling had no influence on atherosclerosis size; this latter measure was only roughly determined by the amount of CHOL food eaten.

  8. How does the ketogenic diet induce anti-seizure effects?

    Science.gov (United States)

    Rho, Jong M

    2017-01-10

    The high-fat ketogenic diet (KD) is a remarkably effective treatment for medically intractable epilepsy and has been part of the clinical armamentarium for nearly a century. However, the mechanisms underlying the KD's actions have remained elusive. Over the past decade, there has been phenomenal international growth of clinical centers offering metabolism-based therapies for epilepsy, and rapidly expanding research into the cellular and biochemical effects induced by the KD. At present, there are many hypotheses regarding KD action, and while each is uniquely compelling, it is becoming more apparent that the KD likely works through multiple mechanisms that target fundamental biochemical pathways linked to cellular substrates (e.g., ion channels) and mediators responsible for neuronal hyperexcitability. This is not altogether surprising given the complexity of the epileptic brain, and the many different pathophysiologic mechanisms that underlie seizure genesis and epileptogenicity. The scientific literature involving the KD strongly supports the notion that epilepsy may indeed in part represent a "metabolic disease", and that this concept could serve as a novel framework for the development of more effective anti-seizure drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  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

  10. Long-term voluntary running improves diet-induced adiposity in young adult mice

    Science.gov (United States)

    The present study investigated the effects of long-term voluntary running on diet-induced adiposity in male C57BL/6 mice. Four-week old mice (n = 15 per group) were fed the AIN93G diet or a 45% high-fat diet (% kcal.) with or without access to in-cage activity wheels for 14 weeks. The high-fat die...

  11. Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

    Science.gov (United States)

    Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

    2016-05-23

    The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

  12. Antiseizure effects of ketogenic diet on seizures induced with ...

    African Journals Online (AJOL)

    The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental ...

  13. Predictors of diet-induced weight loss in overweight adults with type 2 diabetes

    NARCIS (Netherlands)

    Berk, K.A.; Mulder, M.T.; Verhoeven, A.J.M.; Wietmarschen, H. van; Boessen, R.; Pellis, L.P.; Spijker, A.T. van; Timman, R.; Ozcan, B.; Sijbrands, E.J.G.

    2016-01-01

    Aims A very low calorie diet improves the metabolic regulation of obesity related type 2 diabetes, but not for all patients, which leads to frustration in patients and professionals alike. The aim of this study was to develop a prediction model of diet-induced weight loss in type 2 diabetes. Methods

  14. Oral-tolerance induction in diet-induced obese mice.

    Science.gov (United States)

    Mito, Natsuko; Kaburagi, Tomoko; Yoshino, Haruka; Imai, Atsuko; Sato, Kazuto

    2006-08-08

    It is known that immune functions are altered in various ways by obesity. However, changes in the intestinal immune system resulting from obesity remain poorly understood. Oral tolerance is a system that suppresses antigen specific immune responses to orally administrated antigens. The intestinal immune system is intimately associated with the oral tolerance system, that acts to prevent allergic and inflammatory diseases. In this study we investigated the effect of obesity on induction of oral tolerance to ovalbumin (OVA) in an animal model of obesity. Obese mice induced by a high fat diet and control mice were allowed free access for 3 days to a 1%-ovalbumin (OVA) solution in drinking water. After continuous feeding of the antigen, all the mice were immunized by two intraperitoneal injections of OVA administered 7 days apart. In the control mice, induction of oral tolerance caused an increase in antigen specific IgG1 levels and a decrease in IgG2a levels. In contrast, the IgG1/IgG2a ratio was reversed in obese mice. OVA-specific IL-2 production was suppressed by antigen feeding in both the control and obese mice; however, suppression of OVA-specific IL-10 was observed only in the control mice. Although OVA-specific IgA and IgM were not affected by antigen feeding, the obese groups of mice had significantly lower titers of antibodies. These findings suggest that obesity may affect induction of oral tolerance following antigen feeding and that these changes may be related to the inflammatory reaction.

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

    Science.gov (United States)

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

    2012-09-01

    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 in liver of C57BL/6J high-fat diet-induced obese mice. Acute oral administration of 50-300 mg/kg HB to obese mice resulted in a dose-dependent decrease in fasting blood glucose within 3 h of treatment. Daily chronic administration of HB (50 mg/kg for 8 wk) ameliorated hyperglycemia and improved oral glucose tolerance associated with obesity without significantly affecting body weight or body composition. These changes were accompanied by lower expression of two key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase), and increased phosphorylation of AMP-activated protein kinase in the liver and muscle tissue. In vitro, HB treatment (1-15 μM) inhibited cyclic AMP-stimulated but not dexamethasone-stimulated upregulation of PEPCK and G-6-Pase mRNA levels in H4IIE rat hepatoma cells. Among a series of brassinosteroid analogs related to HB, only homocastasterone decreased glucose production in cell culture significantly. These results indicate the antidiabetic effects of brassinosteroids and begin to elucidate their putative cellular targets both in vitro and in vivo.

  16. Effects of exercise and diet change on cognition function and synaptic plasticity in high fat diet induced obese rats.

    Science.gov (United States)

    Woo, Jinhee; Shin, Ki Ok; Park, So Young; Jang, Ki Soeng; Kang, Sunghwun

    2013-10-08

    Nutritional imbalance-induced obesity causes a variety of diseases and in particular is an important cause of cognitive function decline. This study was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced obesity in connection to the effects of regular exercise and dietary control for 8 weeks on the synaptic plasticity and cognitive abilities of brain. Four weeks-old SD rats were adopted classified into normal-normal diet-sedentary (NNS, n = 8), obesity-high fat diet-sedentary (OHS, n = 8), obesity-high fat diet-training (OHT, n = 8), obesity-normal diet-sedentary (ONS, n = 8) and obesity- normal diet-training (ONT, n = 8). The exercise program consisted of a treadmill exercise administered at a speed of 8 m/min for 1-4 weeks, and 14 m/min for 5-8 weeks. The Western blot method was used to measure the expression of NGF, BDNF, p38MAPK and p-p38MAPK proteins in hippocampus of the brain, and expressions of NGF, BDNF, TrkA, TrkB, CREB and synapsin1 mRNA were analyzed through qRT-PCR. The results suggest cognitive function-related protein levels and mRNA expression to be significantly decreased in the hippocampus of obese rats, and synaptic plasticity as well as cognitive function signaling sub-pathway factors were also significantly decreased. In addition, 8-weeks exercises and treatment by dietary change had induced significant increase of cognitive function-related protein levels and mRNA expression as well as synaptic plasticity and cognitive function signaling sub-pathway factors in obese rats. In particular, the combined treatment had presented even more positive effect. Therefore, it was determined that the high fat diet-induced obesity decreases plasticity and cognitive function of the brain, but was identified as being improved by exercises and dietary changes. In particular, it is considered that regular exercise has positive effects on memory span and learning capacity unlike dietary control.

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

    DEFF Research Database (Denmark)

    Fjære, Even

    gluconeogenesis and ureagenesis, in addition to genes related to thermogenesis. Fish oil enriched diets with polyunsaturated omega-3 fatty acids, are shown to prevent diet-induced obesity, however, this effect was blunted with increased sucrose content in the diet. The obesogenic high fat/high diet in combination...

  18. Modulatory role of chelating agents in diet-induced hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Heba M. Mahmoud

    2014-06-01

    Conclusion: Pretreatment of hypercholesterolemic rats with simvastatin, CaNa2EDTA or DMSA attenuated most of the changes induced by feeding rats with cholesterol-rich diet owing to their observed anti-hyperlipidemic and antioxidant properties.

  19. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    National Research Council Canada - National Science Library

    Eduardo R. Ropelle; José R. Pauli; Patrícia Prada; Dennys E. Cintra; Guilherme Z. Rocha; Juliana C. Moraes; Marisa J. S. Frederico; Gabrielle da Luz; Ricardo A. Pinho; José B. C. Carvalheira; Licio A. Velloso; Mario A. Saad; Cláudio T. De Souza

    2009-01-01

    ... in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats...

  20. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    NARCIS (Netherlands)

    Drongelen, J. van; Koppen, A. van; Pertijs, J.C.L.M.; Gooi, J.H.; Parry, L.J.; Sweep, F.C.; Lotgering, F.K.; Smits, P.; Spaanderman, M.E.A.

    2012-01-01

    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

  1. Sirt1 Protects against High-Fat Diet-Induced Metabolic Damage

    National Research Council Canada - National Science Library

    Paul T. Pfluger; Daniel Herranz; Susana Velasco-Miguel; Manuel Serrano; Matthias H. Tschöp

    2008-01-01

    .... Mammalian Sirt1 is a protein deacetylase that has been involved in resveratrol-mediated protection from high-fat diet-induced metabolic damage, but direct proof for the implication of Sirt1 has remained elusive...

  2. Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes

    National Research Council Canada - National Science Library

    Igosheva, Natalia; Abramov, Andrey Y; Poston, Lucilla; Eckert, Judith J; Fleming, Tom P; Duchen, Michael R; McConnell, Josie

    2010-01-01

    ... embryogenesis.Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms...

  3. 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.

  4. Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Bhathena J

    2011-06-01

    Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

  5. 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...

  6. High dietary protein decreases fat deposition induced by high-fat and high-sucrose diet in rats

    NARCIS (Netherlands)

    Chaumontet, C.; Even, P.C.; Schwarz, Jessica; Simonin-Foucault, A.; Piedcoq, J.; Fromentin, G.; Tomé, D.; Azzout-Marniche, D.

    2015-01-01

    High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the

  7. Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases.

    Science.gov (United States)

    Maithilikarpagaselvi, Nachimuthu; Sridhar, Magadi Gopalakrishna; Swaminathan, Rathinam Palamalai; Zachariah, Bobby

    2016-01-25

    Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity.

    Science.gov (United States)

    Juarez, Esther; Tufiño, Cecilia; Querejeta, Enrique; Bracho-Valdes, Ismael; Bobadilla-Lugo, Rosa A

    2017-11-01

    To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α 1 adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD 2 hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.

  9. Diet, microbial virulence, and Helicobacter pylori-induced gastric cancer.

    Science.gov (United States)

    Cover, Timothy L; Peek, Richard M

    2013-01-01

    Gastric adenocarcinoma is a leading cause of cancer-related death worldwide, and Helicobacter pylori infection is one of the strongest known risk factors for this malignancy. H. pylori strains exhibit a high level of genetic diversity, and the risk of gastric cancer is higher in persons carrying certain strain types (for example, those that contain a cag pathogenicity island or type s1 vacA alleles) than in persons carrying other strain types. Additional risk factors for gastric cancer include specific human genetic polymorphisms and specific dietary preferences (for example, a high-salt diet or a diet deficient in fruits and vegetables). Finally, iron-deficiency anemia is a risk factor for gastric cancer. Recent studies have provided evidence that several dietary risk factors for gastric cancer directly impact H. pylori virulence. In this review article, we discuss mechanisms by which diet can modulate H. pylori virulence and thereby influence gastric cancer risk.

  10. Effect of diet fermentability and unsaturated fatty acid concentration on recovery from diet-induced milk fat depression.

    Science.gov (United States)

    Rico, D E; Holloway, A W; Harvatine, K J

    2015-11-01

    Diet-induced milk fat depression is caused by highly fermentable and high-unsaturated fatty acid (FA) diets, and results in reduced milk fat concentration and yield, reduced de novo FA, and increased trans isomers of the alternate biohydrogenation pathways. The hypothesis of the current experiment was that a diet higher in fermentability and lower in unsaturated FA (UFA) would accelerate recovery compared with a high-UFA and lower-fermentability diet. Eight ruminally cannulated and 9 noncannulated multiparous Holstein cows were randomly assigned to treatment sequences in a replicated Latin square design. During each period milk fat depression was induced for 10 d by feeding a low-fiber, high-UFA diet [25.9% neutral detergent fiber (NDF) and 3.3% C18:2]. Following the induction phase, cows were switched to recovery treatments for 18 d designed to correct dietary fermentability, UFA, or both fermentability and UFA concentration. Treatments during recovery were (1) correction of fiber and UFA diet [control; 31.8% NDF and 1.65% C18:2], (2) a diet predominantly correcting fiber, but not UFA [high oil (HO); 31.3% NDF and 2.99% C18:2], and (3) a diet predominantly correcting UFA, but not fiber concentration [low fiber (LF); 28.4% NDF and 1.71% C18:2]. Milk and milk component yield, milk FA profile, ruminal pH, and 11 rumen microbial taxa were measured every third day during recovery. Milk yield decreased progressively in HO and control, whereas it was maintained in the LF diet. Milk fat concentration increased progressively during recovery in all treatments, but was on average 9% lower in LF than control from d 12 to 18. Milk fat yield increased progressively in all treatments and was not different between control and LF at any time point, but was lower in HO than control on d 15. Milk trans-10 C18:1 and trans-10,cis-12 conjugated linoleic acid decreased progressively in all treatments, but was higher in HO than control from d 3 to 18 [136 ± 50 and 188 ± 57% (mean ± SD

  11. Effect of Coleus forskohlii extract on cafeteria diet-induced obesity in rats.

    Science.gov (United States)

    Shivaprasad, Hebbani Nagarajappa; Gopalakrishna, Sushma; Mariyanna, Bhanumathy; Thekkoot, Midhun; Reddy, Roopa; Tippeswamy, Boreddy Shivanandappa

    2014-01-01

    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. The aim of this study was to evaluate antiobesogenic and metabolic benefits of C. forskohlii in cafeteria diet induced obesity rat model. 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. 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. The observed effects validate that supplementation of CFE with cafeteria diet could curb the appetite and mitigate the development of dyslipidemia.

  12. Caralluma fimbriata and metformin protection of rat pancreas from high fat diet induced oxidative stress.

    Science.gov (United States)

    Sudhakara, G; Mallaiah, P; Rajendran, R; Saralakumari, D

    2018-02-01

    A high fat diet promotes oxidative stress, which contributes to the development of pancreatic fibrosis. We compared the protective effects of a hydroalcoholic extract of Caralluma fimbriata (CFE) to metformin (Met) in the pancreas of Wistar rats fed a high fat diet. The experimental animals were divided into five groups: control (C), treated with CFE (C + CFE), treated with high fat diet (HFD), high fat diet treated with CFE (HFD + CFE), and high fat diet treated with metformin (Met) (HFD + Met). CFE was administered orally to groups C + CFE and HFD + CFE rats for 90 days. Met was given to the HFD + Met group. After 90 days, oxidative stress markers in the pancreas including reduced glutathione (GSH), lipid oxidation (LO), protein oxidation (PO), and activities of antioxidant and polyol pathway enzymes, aldose reductase (AR) and sorbitol dehydrogenase (SDH) were assayed and tissue histology was examined. Establishment of oxidative stress in high fat diet fed rats was verified by elevated LO and PO, decreased GSH, decreased activities of antioxidants and increased activities of polyol pathway enzymes. Oxidative stress was prevented in HFD + CFE and HFD + Met groups. Group C + CFE exhibited improved antioxidant status compared to group C. CFE treatment prevented high fat diet induced acinar cell degeneration, necrosis, edema and hemorrhage. CFE could be used as adjuvant therapy for preventing or managing high fat diet induced pancreatic damage.

  13. Effect of diet-induced weight loss on endothelial dysfunction: early improvement after the first week of dieting.

    Science.gov (United States)

    Mavri, Alenka; Poredoš, Peter; Suran, David; Gaborit, Benedicte; Juhan-Vague, Irène; Poredoš, Pavel

    2011-01-01

    Obesity is associated with impaired endothelial function, and this may lead to increased cardiovascular risk. To gain insight into the beneficial effects of diet-induced weight loss on endothelial function, endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery and several metabolic and inflammatory markers were assessed in 40 obese women (BMI 34.9 ± 4.88 kg/m(2)) at baseline, after the 1st week and after 5 months on a low-calorie diet of 5.0 MJ/day. Twenty lean women served as controls. At entry, the obese women had a lower FMD than the lean women (7.7 ± 1.8 vs. 11.5 ± 4.2%, p dieting and continued during the following months of this simple non-pharmacological lifestyle modification to reach normalisation of endothelial function. The favourable effect of dieting on endothelial function is independent of the accompanying improvement of classical risk factors.

  14. Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

    Directory of Open Access Journals (Sweden)

    Hilda Vargas-Robles

    2015-01-01

    Full Text Available Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD. Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

  15. Improvement of Diet-induced Obesity by Ingestion of Mushroom Chitosan Prepared from Flammulina velutipes.

    Science.gov (United States)

    Miyazawa, Noriko; Yoshimoto, Hiroaki; Kurihara, Shoichi; Hamaya, Tadao; Eguchi, Fumio

    2018-02-01

    The anti-obesity effects of mushroom chitosan prepared from Flammulina velutipes were investigated using an animal model with diet-induced obesity. In this study, 5-week-old imprinting control region (ICR) mice were divided into six groups of 10 mice each and fed different diets based on the MF powdered diet (standard diet) for 6 weeks: standard diet control group, high-fat diet control group (induced dietary obesity) consisting of the standard diet and 20% lard, and mushroom chitosan groups consisting of the high-fat diet with mushroom chitosan added at 100, 500, 1,000, and 2,000 mg/kg body weight. On the final day of the experiment, mean body weight was 39.1 g in the high-fat control group and 36.3 g in the 2,000 mg/kg mushroom chitosan group, compared to 35.8 g in the standard diet control group. In the mushroom chitosan groups, a dose-dependent suppression of weight gain and marked improvements in serum triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol were found. The mushroom chitosan groups showed fewer and smaller fat deposits in liver cells than the high-fat diet control group, and liver weight was significantly reduced. Glutamic oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase (GPT), which are indices of the hepatic function, all showed dose-dependent improvement with mushroom chitosan administration. These results suggested that mushroom chitosan acts to suppress enlargement of the liver from fat deposition resulting from a high-fat diet and to restore hepatic function. The lipid content of feces showed a marked increase correlated with the mushroom chitosan dose. These findings suggest the potential use of mushroom chitosan as a functional food ingredient that contributes to the prevention or improvement of dietary obesity by inhibiting digestion and absorption of fats in the digestive tract and simultaneously promotes lipolysis in adipocytes.

  16. Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions

    Directory of Open Access Journals (Sweden)

    Jessica E. Beilharz

    2015-08-01

    Full Text Available It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF. Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

  17. Simultaneous introduction of a novel high fat diet and wheel running induces anorexia.

    Science.gov (United States)

    Scarpace, E T; Matheny, M; Strehler, K Y E; Shapiro, A; Cheng, K Y; Tümer, N; Scarpace, P J

    2012-02-28

    Voluntary wheel running (WR) is a form of physical activity in rodents that influences ingestive behavior. The present report describes an anorexic behavior triggered by the simultaneous introduction of a novel diet and WR. This study examined the sequential, compared with the simultaneous, introduction of a novel high-fat (HF) diet and voluntary WR in rats of three different ages and revealed a surprising finding; the simultaneous introduction of HF food and voluntary WR induced a behavior in which the animals chose not to eat although food was available at all times. This phenomenon was apparently not due to an aversion to the novel HF diet because introduction of the running wheels plus the HF diet, while continuing the availability of the normal chow diet did not prevent the anorexia. Moreover, the anorexia was prevented with prior exposure to the HF diet. In addition, the anorexia was not related to extent of WR but dependent on the act of WR. The introduction a HF diet and locked running wheels did not induce the anorexia. This voluntary anorexia was accompanied by substantial weight loss, and the anorexia was rapidly reversed by removal of the running wheels. Moreover, the HF/WR-induced anorexia is preserved across the age span despite the intrinsic decrease in WR activity and increased consumption of HF food with advancing age. The described phenomenon provides a new model to investigate anorexia behavior in rodents. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue

    NARCIS (Netherlands)

    Schafer, M.J.; White, T.A.; Evans, G.; Tonne, J.M.; Verzosa, G.C.; Stout, M.B.; Mazula, D.L.; Palmer, A.K.; Baker, D.J.; Jensen, M.D.; Torbenson, M.S.; Miller, J.D.; Ikeda, Y.; Tchkonia, T.; Deursen, J.M.A. van; Kirkland, J.L.; LeBrasseur, N.K.

    2016-01-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the

  19. Inflammatory mediators in diet-induced cardiac dysfunction

    NARCIS (Netherlands)

    Louwe, Maria Cornelia (Mieke)

    2013-01-01

    The studies in this thesis are performed to provide additional and improved insight into the effects and interplay of dietary lipids and metabolic inflammation on cardiac performance in the presence or absence of atherosclerosis and myocardial infarctions (MI). We show that high-fat diet feeding has

  20. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  1. Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters.

    Science.gov (United States)

    Rideout, Todd C; Ramprasath, Vanu; Griffin, John D; Browne, Richard W; Harding, Scott V; Jones, Peter J H

    2014-01-06

    In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known. We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n = 12/group). An additional subset of animals (n = 12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties. In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Aldose reductase is involved in the development of murine diet-induced nonalcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Longxin Qiu

    Full Text Available Hepatic aldose reductase (AR expression is known to be induced in liver diseases, including hepatitis and hepatocellular carcinoma. However, the role of AR in the development of these diseases remains unclear. We performed this current study to determine whether and how AR might be involved in the development of diet-induced nonalcoholic steatohepatitis. Our results showed that the level of AR protein expression was significantly higher in db/db mice fed the methionine-choline-deficient (MCD diet than in mice fed the control diet. In parallel with the elevation in AR, steatohepatitis was observed in MCD diet-fed mice, and this diet-induced steatohepatitis was significantly attenuated by lentiviral-mediated knock-down of the AR gene. This suppressive effect of AR knock-down was associated with repressed levels of serum alanine aminotransferase and hepatic lipoperoxides, reduced mRNA and protein expression of hepatic cytochrome P450 2E1 (CYP2E1, and decreased mRNA expression of pro-inflammatory tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6. Moreover, AR-induced elevations on the level of CYP2E1 expression, reactive oxygen species, mRNA expression of TNF-α and IL-6 were confirmed in AML12 hepatocytes. Further, lentiviral-mediated knock-down of AR ameliorated MCD diet-induced collagen deposition in the livers of db/db mice. With the improvement in liver fibrosis, the mRNA levels of tissue inhibitor of metalloproteinase-1 (TIMP-1 and matrix metalloproteinase-2 (MMP-2, two genes involved in hepatic fibrogenesis, were found to be significantly suppressed, while TIMP-2 and MMP-13 were unaffected. Together these data indicate that inhibition of AR alleviates the MCD diet-induced liver inflammation and fibrosis in db/db mice, probably through dampening CYP2E1 mediated-oxidative stress and ameliorating the expression of pro-inflammatory cytokines.

  4. Helicobacter pylori Infection Aggravates Diet-induced Insulin Resistance in Association With Gut Microbiota of Mice

    Directory of Open Access Journals (Sweden)

    Cong He

    2016-10-01

    Full Text Available Emerging evidence suggests that Helicobacter pylori infection is associated with insulin resistance (IR yet the underlying mechanisms are still obscure. The vital role of gut microbiota in triggering IR has been increasingly reported, however, no study has explored the correlation of gut microbiota and H. pylori-associated IR. Using H. pylori-infected mice model fed different diet structures, we demonstrated that H. pylori infection significantly aggravated high-fat diet (HFD-induced metabolic disorders at the early stage, the extent of which was close to the effect of long-term HFD. Interestingly, we observed dynamic alterations in gut microbiota that were consistent with the changes in the metabolic phenotype induced by H. pylori and HFD. There may be an interaction among H. pylori, diet and gut microbiota, which dysregulates the host metabolic homeostasis, and treatment of H. pylori may be beneficial to the patients with impaired glucose tolerance in addition to diet control.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Effects of Proportions of Dietary Macronutrients on Glucocorticoid Metabolism in Diet-Induced Obesity in Rats

    Science.gov (United States)

    Stimson, Roland H.; Lobley, Gerald E.; Maraki, Ioanna; Morton, Nicholas M.; Andrew, Ruth; Walker, Brian R.

    2010-01-01

    Tissue glucocorticoid levels in the liver and adipose tissue are regulated by regeneration of inactive glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and inactivation by 5α- and 5β-reductases. A low carbohydrate diet increases hepatic 11β-HSD1 and reduces glucocorticoid metabolism during weight loss in obese humans. We hypothesized that similar variations in macronutrient proportions regulate glucocorticoid metabolism in obese rats. Male Lister Hooded rats were fed an obesity-inducing ad libitum ‘Western’ diet (37% fat, n = 36) for 22 weeks, then randomised to continue this diet (n = 12) or to switch to either a low carbohydrate (n = 12) or a moderate carbohydrate (n = 12) diet for the final 8 weeks. A parallel lean control group were fed an ad libitum control diet (10% fat, n = 12) throughout. The low and moderate carbohydrate diets decreased hepatic 11β-HSD1 mRNA compared with the Western diet (both 0.7±0.0 vs 0.9±0.1 AU; pdiet. Compared with lean controls, the Western diet decreased 11β-HSD1 activity (1.6±0.1 vs 2.8±0.1 nmol/mcg protein/hr; pobesity-inducing high fat diet in rats recapitulates the abnormal glucocorticoid metabolism associated with human obesity in liver (but not in adipose tissue), a low carbohydrate diet does not increase hepatic 11β-HSD1 in obese rats as occurs in humans. PMID:20098742

  7. Use of hamster as a model to study diet-induced atherosclerosis

    OpenAIRE

    Lichtenstein Alice H; Matthan Nirupa R; Dillard Alice

    2010-01-01

    Abstract Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diet...

  8. Helicobacter pylori Infection Aggravates Diet-induced Insulin Resistance in Association With Gut Microbiota of Mice

    OpenAIRE

    He, Cong; Yang, Zhen; Cheng, Dandan; Xie, Chuan; Zhu, Yin; Ge, Zhongming; Luo, Zhijun; Lu, Nonghua

    2016-01-01

    Emerging evidence suggests that Helicobacter pylori infection is associated with insulin resistance (IR) yet the underlying mechanisms are still obscure. The vital role of gut microbiota in triggering IR has been increasingly reported, however, no study has explored the correlation of gut microbiota and H. pylori-associated IR. Using H. pylori-infected mice model fed different diet structures, we demonstrated that H. pylori infection significantly aggravated high-fat diet (HFD)-induced metabo...

  9. Fresh garlic amelioration of high-fat-diet induced fatty liver in albino rats.

    Science.gov (United States)

    Qamar, Aisha; Siddiqui, Asma; Kumar, Hemant

    2015-10-01

    To observe the effect of fresh garlic on high-fat-diet-induced fatty liver changes. The experimental study was conducted at the Jinnah Postgraduate Medical Centre, Karachi, from October to November 2008, and comprised adult albino rats weighing 200-240g each. The rats were divided into 5 groups according to dietary regimen for eight weeks each. Group A received control diet; Group B received high saturated fat diet; Group C received high unsaturated fat diet; Group D received high saturated fat diet with fresh garlic; and Group E received high unsaturated fat diet with garlic for 8 weeks. Liver tissue slides were stained with Oil red-O and haematoxylin and Periodic acid-Schiff-haematoxylin. The 50 rats in the study were divided into five groups of 10(20%) each. There was marked deposition of fat in hepatocyte along with marked decrease in glycogen content in liver of rats in Groups B and C, with Group B showing more marked changes. The changes in fat and glycogen content were reversed and ameliorated close to Group A in rats belonging to Groups D and E. Fresh garlic minimised the high-fat-diet-induced fatty liver changes in rats.

  10. Antiseizure Effects of Ketogenic Diet on Seizures Induced with ...

    African Journals Online (AJOL)

    olayemitoyin

    *1E.O. Sanya, 2A. O. Soladoye, 1O.O. Desalu, 1P. M. Kolo, 2L. A. Olatunji, 1J. K. Olarinoye. Departments of 1Medicine and 2Physiology, University of Ilorin, Ilorin, Nigeria. Summary: The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the ...

  11. No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial.

    Science.gov (United States)

    Kuzma, Jessica N; Cromer, Gail; Hagman, Derek K; Breymeyer, Kara L; Roth, Christian L; Foster-Schubert, Karen E; Holte, Sarah E; Weigle, David S; Kratz, Mario

    2016-08-01

    Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation. We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). Excessive amounts of fructose, HFCS, and glucose from SSBs

  12. Antiobesity effect of Safoof Mohazzil, a polyherbal formulation, in cafeteria diet induced obesity in rats.

    Science.gov (United States)

    Gupta, Pooja; Mehla, Jogender; Gupta, Yogendra Kumar

    2012-11-01

    Obesity is reaching epidemic proportions all over the world yet it lacks adequate treatment. Most of the drugs have failed either due to ineffectiveness or adverse effects. Complementary and alternative system of medicine is being used since ancient times. However, many of them have not been tested for efficacy and safety using modern scientific methods. Therefore, the antiobesity effect of Safoof Mohazzil, a polyherbal formulation, was evaluated in cafeteria diet induced obesity in female Sprague Dawley rats. Animals weighing 100-150 g were divided into four groups (n = 8) i.e. standard pellet diet, cafeteria diet control, cafeteria diet + Safoof Mohazzil and standard pellet diet plus Safoof Mohazzil. The formulation was administered orally at a dose of 1 g/kg/day for 14 weeks. At the end of study, cafeteria diet significantly increased body weight, Lee's index, lipid profile (cholesterol and triglycerides), insulin and leptin levels as compared to standard pellet diet control group. Fourteen week treatment with Safoof Mohazzil significantly prevented the increase in body weight, Lee's index, lipid profile, insulin and leptin levels as compared to cafeteria diet control group without affecting food and water intake. Safoof Mohazzil had no adverse effect on hepatic transaminases, locomotor activity and motor coordination. The study provides evidence for antiobesity effect of Safoof Mohazzil.

  13. Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

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    O. S. Adeyemi

    2014-01-01

    Full Text Available Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4 in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity.

  14. Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

    Science.gov (United States)

    Adeyemi, O. S.; Elebiyo, T. C.

    2014-01-01

    Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4) in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity. PMID:25295181

  15. PTPRT regulates high-fat diet-induced obesity and insulin resistance.

    Science.gov (United States)

    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 reduced food intake. Consistently, STAT3 phosphorylation is up-regulated in the hypothalamus of PTPRT knockout mice. These studies implicate PTPRT-modulated STAT3 signaling in the regulation of high-fat diet-induced obesity.

  16. 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

    2013-04-03

    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. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats

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    Cristiano Mostarda

    2012-07-01

    Full Text Available OBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F in drinking water (100 g/l were concomitantly trained on a treadmill (FT for 10 weeks or kept sedentary. These rats were compared with a control group (C. Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz, and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 ± 0.2 vs. C: 4.5 ± 0.2 mg/dl/min, hypertension (mean blood pressure, F: 118 ± 3 vs. C: 104 ± 4 mmHg and obesity (F: 0.31±0.001 vs. C: 0.29 ± 0.001 g/mm. Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

  18. Effect of Creosote Bush-Derived NDGA on Expression of Genes Involved in Lipid Metabolism in Liver of High-Fructose Fed Rats: Relevance to NDGA Amelioration of Hypertriglyceridemia and Hepatic Steatosis.

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    Haiyan Zhang

    Full Text Available Nordihydroguaiaretic acid (NDGA, the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS, lowering blood glucose, free fatty acids (FFA and triglyceride (TG levels in several models of dyslipidemia, as well as improving body weight (obesity, insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36, and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors. Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt, AMPK activity (P-AMPK, MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1. These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

  19. The Ketogenic Diet Suppresses the Cathepsin E Expression Induced by Kainic Acid in the Rat Brain

    Science.gov (United States)

    Jeong, Hyun Jeong; Kim, Hojeong; Kim, Yoon-Kyoung; Park, Sang-Kyu; Kang, Dong-Won

    2010-01-01

    Purpose The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, we analyzed the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model. Materials and Methods KA-administered rats were fed the ketogenic diet or a normal diet for 4 weeks, and microarray analysis was performed with their brain tissues. The effects of the ketogenic diet on cathepsin E messenger ribonucleic acid (mRNA) expression were analyzed in KA-administered and normal saline-administered groups with semi-quantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Brain tissues were dissected into 8 regions to compare differential effects of the ketogenic diet on cathepsin E mRNA expression. Immunohistochemistry with an anti-cathepsin E antibody was performed on slides of hippocampus obtained from whole brain paraffin blocks. Results The microarray data and subsequent RT-PCR experiments showed that KA increased the mRNA expression of cathepsin E, known to be related to neuronal cell death, in most brain areas except the brain stem, and these increases of cathepsin E mRNA expression were suppressed by the ketogenic diet. The expression of cathepsin E mRNA in the control group, however, was not significantly affected by the ketogenic diet. The change in cathepsin E mRNA expression was greatest in the hippocampus. The protein level of cathepsin E in the hippocampus of KA-administered rat was elevated in immunohistochemistry and the ketogenic diet suppressed this increase. Conclusion Our results showed that KA administration increased cathepsin E expression in the rat brain and its increase was suppressed by the ketogenic diet. PMID:20635438

  20. Metabolomic and Lipidomic Analysis of Serum Samples following Curcuma longa Extract Supplementation in High-Fructose and Saturated Fat Fed Rats.

    Science.gov (United States)

    Tranchida, Fabrice; Shintu, Laetitia; Rakotoniaina, Zo; Tchiakpe, Léopold; Deyris, Valérie; Hiol, Abel; Caldarelli, Stefano

    2015-01-01

    We explored, using nuclear magnetic resonance (NMR) metabolomics and fatty acids profiling, the effects of a common nutritional complement, Curcuma longa, at a nutritionally relevant dose with human use, administered in conjunction with an unbalanced diet. Indeed, traditional food supplements have been long used to counter metabolic impairments induced by unbalanced diets. Here, rats were fed either a standard diet, a high level of fructose and saturated fatty acid (HFS) diet, a diet common to western countries and that certainly contributes to the epidemic of insulin resistance (IR) syndrome, or a HFS diet with a Curcuma longa extract (1% of curcuminoids in the extract) for ten weeks. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) on the serum NMR profiles and fatty acid composition (determined by GC/MS) showed a clear discrimination between HFS groups and controls. This discrimination involved metabolites such as glucose, amino acids, pyruvate, creatine, phosphocholine/glycerophosphocholine, ketone bodies and glycoproteins as well as an increase of monounsaturated fatty acids (MUFAs) and a decrease of n-6 and n-3 polyunsaturated fatty acids (PUFAs). Although the administration of Curcuma longa did not prevent the observed increase of glucose, triglycerides, cholesterol and insulin levels, discriminating metabolites were observed between groups fed HFS alone or with addition of a Curcuma longa extract, namely some MUFA and n-3 PUFA, glycoproteins, glutamine, and methanol, suggesting that curcuminoids may act respectively on the fatty acid metabolism, the hexosamine biosynthesis pathway and alcohol oxidation. Curcuma longa extract supplementation appears to be beneficial in these metabolic pathways in rats. This metabolomic approach highlights important serum metabolites that could help in understanding further the metabolic mechanisms leading to IR.

  1. Hypolipidemic activity of Haritaki (Terminalia chebula in atherogenic diet induced hyperlipidemic rats

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    V Maruthappan

    2010-01-01

    Full Text Available Haritaki (Terminalia chebula family Combretaceae is an important plant used traditionally for medicinal purposes. It is component of the classic Ayurvedic combination called "Triphala". Hyperlipidemia was induced by treated orally with atherogemc diet. In atherogenic diet induced hyperlipidemic model, the rats receiving treatment with Haritaki showed significant reduction in total cholesterol, triglycerides, total protein and elevation of high density lipoprotein cholesterol. Haritaki was found to possess significant hypolipidemic activity. The results also suggest that Haritaki at 1.05 and 2.10 mg/kg b.wt. concentrations are an excellent lipid-lowering agent.

  2. HYPOLIPIDEMIC ACTIVITY OF HARITAKI (TERMINALIA CHEBULA IN ATHEROGENIC DIET INDUCED HYPERLIPIDEMIC RATS

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    V. Maruthappan

    2010-06-01

    Full Text Available Haritaki (Terminalia chebula family Combretaceae is an important plant used traditionally for medicinal purposes. It is component of the classic Ayurvedic combination called “Triphala”. Hyperlipidemia was induced by treated orally with atherogenic diet. In atherogenic diet induced hyperlipidemic model, the rats receiving treatment with Haritaki showed significant reduction in total cholesterol, triglycerides, total protein and elevation of high density lipoprotein cholesterol. Haritaki was found to possess significant hypolipidemic activity. The results also suggest that Haritaki at 1.05 and 2.10 mg/kg b.wt. concentrations are an excellent lipid-lowering agent.

  3. Fat and carbohydrate content in the diet induces drastic changes in gene expression in young Göttingen minipigs

    DEFF Research Database (Denmark)

    Mentzel, Caroline M.Junker; Figueiredo Cardoso, Tainã; Haagensen, Annika Maria Juul

    2017-01-01

    impact of diet interventions, it is very important to investigate the molecular mechanisms driving the diet-induced phenotypic changes in relevant tissues. However, studying these effects in humans is difficult due to ethical concerns in doing interventions and obtaining tissue samples and good animal...... the initial stages of diet-induced metabolic changes. Half of them were fed a high-fat/cholesterol, low-carbohydrate (HFLC) diet, and the other half were fed a low- fat/cholesterol, high-carbohydrate (LFHC) diet. After 13 weeks, the HFLC group weighted less and had dyslipidemia compared to the LFHC group...

  4. Daming capsule restores endothelial dysfunction induced by high-fat diet

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    Zhang Rong

    2012-03-01

    Full Text Available Abstract Background Daming capsule (DMC, a traditional Chinese formula, has a lipid-modulating action with reduced adverse side effects as compared with other lipid lowering compounds. Since endothelial dysfunction often accompanies the hyperlipidemic state, we hypothesize that DMC might restore endothelial dysfunction produced by a high-fat (HF diet. Importantly, we also investigate possible mechanisms involved in mediating the effects of DMC on vascular reactivity. Methods Rats were divided into four groups: control, HF diet, HF mixed DMC diet, HF mixed atorvastatin (ATV diet. After 30 days, the thoracic cavity was exposed to remove the thoracic aorta for (i histological examination; (ii measurement of endothelial nitric oxide synthase (eNOS by western blot; and (iii tension study of thoracic aortic ring. Results HF diet induced significant attenuation in the contraction and relaxation of rat aortic rings. Treatment with DMC significantly improved the relaxation of the aortic rings as compared with those from HF rats (P + channels (KATP on the structure and/or function. DMC exerted the same protective effect as ATV, a positive control drug, on vascular injury produced by HF diet. Conclusion DMC partially protects the aorta from HF-induced endothelial dysfunction via upregulation of the expression of eNOS.

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

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    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. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  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. A high-fat, ketogenic diet induces a unique metabolic state in mice.

    Science.gov (United States)

    Kennedy, Adam R; Pissios, Pavlos; Otu, Hasan; Roberson, Russell; Xue, Bingzhong; Asakura, Kenji; Furukawa, Noburu; Marino, Frank E; Liu, Fen-Fen; Kahn, Barbara B; Libermann, Towia A; Maratos-Flier, Eleftheria

    2007-06-01

    Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.

  8. Canola oil rich in oleic acid improves diastolic heart function in diet-induced obese rats.

    Science.gov (United States)

    Thandapilly, Sijo Joseph; Raj, Pema; Louis, Xavier Lieben; Perera, Danielle; Yamanagedara, Prasanga; Zahradka, Peter; Taylor, Carla G; Netticadan, Thomas

    2017-05-01

    Obesity is a leading cause of cardiovascular disease. It directly affects heart structure and function and contributes to heart failure. Diet is a major factor involved in the development of obesity along with genetic factors. We examined the effects of monounsaturated and polyunsaturated fatty acid-rich oils on cardiac structure and function in the diet-induced rodent model of obesity (DIO). Obese prone (OP) rats were fed a high-fat diet (HF; 55% of kcal) for 12 weeks; Sprague-Dawley rats fed commercial chow served as control. Echocardiography was performed to assess the cardiac structure and function in all rats at 12 weeks. OP rats fed the HF diet showed significant impairment in diastolic function compared to control rats. The HF diet containing high oleic canola oil significantly improved diastolic function of OP rats compared to the HF diet with lard. In conclusion, canola oil rich in oleic acid, when incorporated into an HF diet, prevents the development of diastolic dysfunction in DIO rats.

  9. Ladder-Climbing Training Prevents Bone Loss and Microarchitecture Deterioration in Diet-Induced Obese Rats.

    Science.gov (United States)

    Tang, Liang; Gao, Xiaohang; Yang, Xiaoying; Liu, Chentao; Wang, Xudan; Han, Yanqi; Zhao, Xinjuan; Chi, Aiping; Sun, Lijun

    2016-01-01

    Resistance exercise has been proved to be effective in improving bone quality in both animal and human studies. However, the issue about whether resistance exercise can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of ladder-climbing training, one of the resistance exercises, on bone mechanical properties and microarchitecture in high-fat (HF) diet-induced obese rats. Twenty-four rats were randomly assigned to the Control, HF + sedentary (HF-S) and HF + ladder-climbing training (HF-LCT) groups. Rats in the HF-LCT group performed ladder-climbing training for 8 weeks. The results showed that ladder-climbing training significantly reduced body and fat weight, and increased muscle mass along with a trend toward enhanced muscle strength in diet-induced obese rats. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by ladder-climbing training, as evidenced by increased trabecular bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor ladder-climbing training had an impact on femoral biomechanical properties. Moreover, ladder-climbing training significantly increased serum adiponectin, decreased serum leptin, TNF-α, IL-6 levels, and downregulated myostatin (MSTN) expression in diet-induced obese rats. Taken together, ladder-climbing training prevents bone loss and microarchitecture deterioration in diet-induced obese rats through multiple mechanisms including increasing mechanical loading on bone due to improved skeletal muscle mass and strength, regulating the levels of myokines and adipokines, and suppressing the release of pro-inflammatory cytokines. It indicates that resistance exercise may be a promising therapy for treating obesity-induced bone loss.

  10. Ruscogenin protects against high-fat diet-induced nonalcoholic steatohepatitis in hamsters.

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    Lu, Hung-Jen; Liou, Shorong-Shii; Chang, Chia Ju; Lin, Sheng Da; Yang, Cheng; Wu, Ming-Chang; Liu, I-Min

    2014-07-01

    The protective effects of ruscogenin on nonalcoholic steatohepatitis in hamsters fed a high-fat diet were investigated. Ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) was orally administered by gavage once daily for eight weeks. A high-fat diet induced increases in plasma levels of total cholesterol, triglycerides, and free fatty acids, while the degree of insulin resistance was lowered by ruscogenin. High-fat diet-induced hepatic steatosis and necroinflammation were improved by ruscogenin. Gene expression of inflammatory cytokines and activity of nuclear transcription factor-κB were also increased in the high-fat diet group, which were attenuted by ruscogenin. Ruscogenin decreased hepatic mRNA levels of sterol regulatory element-binding protein-1c and its lipogenic target genes. The hepatic mRNA expression of peroxisome proliferator-activated receptor α, together with its target genes responsible for fatty acid β-oxidation were upregulated by ruscogenin. In conclusion, these findings suggest that ruscogenin may attenuate high-fat diet-induced steatohepatitis through anti-inflammatory mechanisms, reducing hepatic lipogenic gene expression, and upregulating proteins in the fatty acid oxidation process. Georg Thieme Verlag KG Stuttgart · New York.

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

    Science.gov (United States)

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

    2015-01-01

    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

  12. 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.

  13. Use of hamster as a model to study diet-induced atherosclerosis

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    Lichtenstein Alice H

    2010-12-01

    Full Text Available Abstract Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified and dietary perturbation (cholesterol and/or fat on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA, monounsaturated or n-6 polyunsaturated (PUFA had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s of diet-induced development of atherosclerotic lesions.

  14. Use of hamster as a model to study diet-induced atherosclerosis.

    Science.gov (United States)

    Dillard, Alice; Matthan, Nirupa R; Lichtenstein, Alice H

    2010-12-10

    Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified) and dietary perturbation (cholesterol and/or fat) on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C) than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA), monounsaturated or n-6 polyunsaturated (PUFA) had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s) of diet-induced development of atherosclerotic lesions.

  15. Transgenerational inheritance of diet-induced genome rearrangements in Drosophila.

    Directory of Open Access Journals (Sweden)

    John C Aldrich

    2015-04-01

    Full Text Available Ribosomal RNA gene (rDNA copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila genome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet.

  16. beta3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Macé K

    2004-08-01

    Full Text Available Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of ?3-adrenoceptor (?3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective ?3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.

  17. Diet-induced obesity modulates epigenetic responses to ionizing radiation in mice.

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    Guillaume Vares

    Full Text Available Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6J mice fed a control normal fat or a high fat (HF diet were exposed to fractionated doses of X-rays (0.75 Gy ×4. Bone marrow micronucleus assays did not suggest a modulation of radiation-induced genotoxicity by HF diet. Using MSP, we observed that the promoters of p16 and Dapk genes were methylated in the livers of C57BL/6J mice fed a HF diet (irradiated and non-irradiated; Mgmt promoter was methylated in irradiated and/or HF diet-fed mice. In addition, methylation PCR arrays identified Ep300 and Socs1 (whose promoters exhibited higher methylation levels in non-irradiated HF diet-fed mice as potential targets for further studies. We then compared microRNA regulations after radiation exposure in the livers of C57BL/6J mice fed a normal or an HF diet, using microRNA arrays. Interestingly, radiation-triggered microRNA regulations observed in normal mice were not observed in obese mice. miR-466e was upregulated in non-irradiated obese mice. In vitro free fatty acid (palmitic acid, oleic acid administration sensitized AML12 mouse liver cells to ionizing radiation, but the inhibition of miR-466e counteracted this radio-sensitization, suggesting that the modulation of radiation responses by diet-induced obesity might involve miR-466e expression. All together, our results suggested the existence of dietary effects on radiation responses (especially epigenetic regulations in mice, possibly in relationship with obesity-induced chronic oxidative stress.

  18. Diet-induced obesity modulates epigenetic responses to ionizing radiation in mice.

    Science.gov (United States)

    Vares, Guillaume; Wang, Bing; Ishii-Ohba, Hiroko; Nenoi, Mitsuru; Nakajima, Tetsuo

    2014-01-01

    Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses) and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6J mice fed a control normal fat or a high fat (HF) diet were exposed to fractionated doses of X-rays (0.75 Gy ×4). Bone marrow micronucleus assays did not suggest a modulation of radiation-induced genotoxicity by HF diet. Using MSP, we observed that the promoters of p16 and Dapk genes were methylated in the livers of C57BL/6J mice fed a HF diet (irradiated and non-irradiated); Mgmt promoter was methylated in irradiated and/or HF diet-fed mice. In addition, methylation PCR arrays identified Ep300 and Socs1 (whose promoters exhibited higher methylation levels in non-irradiated HF diet-fed mice) as potential targets for further studies. We then compared microRNA regulations after radiation exposure in the livers of C57BL/6J mice fed a normal or an HF diet, using microRNA arrays. Interestingly, radiation-triggered microRNA regulations observed in normal mice were not observed in obese mice. miR-466e was upregulated in non-irradiated obese mice. In vitro free fatty acid (palmitic acid, oleic acid) administration sensitized AML12 mouse liver cells to ionizing radiation, but the inhibition of miR-466e counteracted this radio-sensitization, suggesting that the modulation of radiation responses by diet-induced obesity might involve miR-466e expression. All together, our results suggested the existence of dietary effects on radiation responses (especially epigenetic regulations) in mice, possibly in relationship with obesity-induced chronic oxidative stress.

  19. Psidium guajava Linn. leaf extract affects hepatic glucose transporter-2 to attenuate early onset of insulin resistance consequent to high fructose intake: An experimental study

    Science.gov (United States)

    Mathur, R.; Dutta, Shagun; Velpandian, T.; Mathur, S.R.

    2015-01-01

    Background: Insulin resistance (IR) is amalgam of pathologies like altered glucos metabolism, dyslipidemia, impaired glucose tolerance, non-alcoholic fatty liver disease, and associated with type-II diabetes and cardiometabolic diseases. One of the reasons leading to its increased and early incidence is understood to be a high intake of processed fructose containing foods and beverages by individuals, especially, during critical developmental years. Objective: To investigate the preventive potential of aqueous extract of Psidium guajava leaves (PG) against metabolic pathologies, vis-à-vis, IR, dyslipidemia, hyperleptinemia and hypertension, due to excess fructose intake initiated during developmental years. Materials and Methods: Post-weaning (4 weeks old) male rats were provided fructose (15%) as drinking solution, ad libitum, for 8 weeks and assessed for food and water/fructose intake, body weight, fasting blood sugar, mean arterial pressure, lipid biochemistry, endocrinal (insulin, leptin), histopathological (fatty liver) and immunohistochemical (hepatic glucose transporter [GLUT2]) parameters. Parallel treatment groups were administered PG in doses of 250 and 500 mg/kg/d, po × 8 weeks and assessed for same parameters. Using extensive liquid chromatography-mass spectrometry protocols, PG was analyzed for the presence of phytoconstituents like Myrecetin, Luteolin, Kaempferol and Guavanoic acid and validated to contain Quercetin up to 9.9%w/w. Results: High fructose intake raised circulating levels of insulin and leptin and hepatic GLUT2 expression to promote IR, dyslipidemia, and hypertension that were favorably re-set with PG. Although PG is known for its beneficial role in diabetes mellitus, for the first time we report its potential in the management of lifelong pathologies arising from high fructose intake initiated during developmental years. PMID:25829790

  20. Purple Sweet Potato Attenuate Weight Gain in High Fat Diet Induced Obese Mice.

    Science.gov (United States)

    Ju, Ronghui; Zheng, Shujuan; Luo, Hongxia; Wang, Changgang; Duan, Lili; Sheng, Yao; Zhao, Changhui; Xu, Wentao; Huang, Kunlun

    2017-03-01

    Purple sweet potato (PSP) is widely grown in Asia and considered as a healthy vegetable. The objective of the current study was to determine the anti-obesity effect of the PSP on high fat diet induced obese C57BL/6J mice. The mice were administrated with high fat diet supplemented with the sweet potato (SP) or PSP at the concentration of 15% and 30% for 12 wk, respectively. The results showed that the supplementation of SP or PSP at 30% significantly ameliorated high fat diet induced obesity and its associated risk factors, including reduction of body weight and fat accumulation, improvement of lipid profile and modulation of energy expenditure. Moreover, PSP also posed beneficial effect on the liver and kidney functions. These results indicate that PSP and SP have anti-obesity effect and are effective to reduce the metabolic risk. © 2017 Institute of Food Technologists®.

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

    Science.gov (United States)

    Kumar, Shiv; Alagawadi, K R; Rao, M Raghavendra

    2011-04-01

    To evaluate the antiobesity effects of the ethanolic extract of Argyreia speciosa roots in rats fed with a cafeteria diet (CD). 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. The body weight at two-to-six weeks and the final parametrial adipose tissue weights were significantly lowered (P cafeteria diet-induced obesity in rats.

  2. Diet-induced weight loss: the effect of dietary protein on bone.

    Science.gov (United States)

    Tang, Minghua; O'Connor, Lauren E; Campbell, Wayne W

    2014-01-01

    High-protein (>30% of energy from protein or >1.2 g/kg/day) and moderately high-protein (22% to 29% of energy from protein or 1.0 to 1.2 g/kg/day) diets are popular for weight loss, but the effect of dietary protein on bone during weight loss is not well understood. Protein may help preserve bone mass during weight loss by stimulating insulin-like growth factor 1, a potent bone anabolism stimulator, and increasing intestinal calcium absorption. Protein-induced acidity is considered to have minimal effect on bone resorption in adults with normal kidney function. Both the quantity and predominant source of protein influence changes in bone with diet-induced weight loss. Higher-protein, high-dairy diets may help attenuate bone loss during weight loss. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  3. 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...... by hydrolyzed casein ingestion translated into decreased body and adipose tissue masses. We conclude that chronic consumption of extensively hydrolyzed casein reduces body mass gain and diet-induced obesity in male C57BL/6J mice....

  4. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons.

    Science.gov (United States)

    de Lartigue, Guillaume; Barbier de la Serre, Claire; Espero, Elvis; Lee, Jennifer; Raybould, Helen E

    2011-07-01

    Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.

  5. Appropriateness of the hamster as a model to study diet-induced atherosclerosis

    Science.gov (United States)

    Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apo...

  6. 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...

  7. Feasibility of simultaneous PET/MR in diet-induced atherosclerotic minipig

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Ludvigsen, Trine Pagh; 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Diet shifts and population dynamics of estuarine foraminifera during ecosystem recovery after experimentally induced hypoxia crises

    NARCIS (Netherlands)

    Brouwer, G.M.; Duijnstee, Ivo; Hazeleger, J.H.; Rossi, F.; Lourens, L.J.; Middelburg, J.J.; Wolthers, M.

    2016-01-01

    This study shows foraminiferal dynamics after experimentally induced hypoxia within the wider context of ecosystem recovery. 13C-labeled bicarbonate and glucose were added to the sediments to examine foraminiferal diet shifts during ecosystem recovery and test-size measurements were used to deduce

  10. Altered Glutathione Homeostasis in Heart Augments Cardiac Lipotoxicity Associated with Diet-induced Obesity in Mice*

    Science.gov (United States)

    Ghosh, Sanjoy; Sulistyoningrum, Dian C.; Glier, Melissa B.; Verchere, C. Bruce; Devlin, Angela M.

    2011-01-01

    Obesity-related cardiac lipid accumulation is associated with increased myocardial oxidative stress. The role of the antioxidant glutathione in cardiac lipotoxicity is unclear. Cystathionine β-synthase (Cbs) catalyzes the first step in the trans-sulfuration of homocysteine to cysteine, which is estimated to provide ∼50% of cysteine for hepatic glutathione biosynthesis. As cardiac glutathione is a reflection of the liver glutathione pool, we hypothesize that mice heterozygous for targeted disruption of Cbs (Cbs+/−) are more susceptible to obesity-related cardiolipotoxicity because of impaired liver glutathione synthesis. Cbs+/+ and Cbs+/− mice were fed a high fat diet (60% energy) from weaning for 13 weeks to induce obesity and had similar increases in body weight and body fat. This was accompanied by increased hepatic triglyceride but no differences in hepatic glutathione levels compared with mice fed chow. However, Cbs+/− mice with diet-induced obesity had greater glucose intolerance and lower total and reduced glutathione levels in the heart, accompanied by lower plasma cysteine levels compared with Cbs+/+ mice. Higher triglyceride concentrations, increased oxidative stress, and increased markers of apoptosis were also observed in heart from Cbs+/− mice with diet-induced obesity compared with Cbs+/+ mice. This study suggests a novel role for Cbs in maintaining the cardiac glutathione pool and protecting against cardiac lipid accumulation and oxidative stress during diet-induced obesity in mice. PMID:22021075

  11. Altered glutathione homeostasis in heart augments cardiac lipotoxicity associated with diet-induced obesity in mice.

    Science.gov (United States)

    Ghosh, Sanjoy; Sulistyoningrum, Dian C; Glier, Melissa B; Verchere, C Bruce; Devlin, Angela M

    2011-12-09

    Obesity-related cardiac lipid accumulation is associated with increased myocardial oxidative stress. The role of the antioxidant glutathione in cardiac lipotoxicity is unclear. Cystathionine β-synthase (Cbs) catalyzes the first step in the trans-sulfuration of homocysteine to cysteine, which is estimated to provide ∼50% of cysteine for hepatic glutathione biosynthesis. As cardiac glutathione is a reflection of the liver glutathione pool, we hypothesize that mice heterozygous for targeted disruption of Cbs (Cbs(+/-)) are more susceptible to obesity-related cardiolipotoxicity because of impaired liver glutathione synthesis. Cbs(+/+) and Cbs(+/-) mice were fed a high fat diet (60% energy) from weaning for 13 weeks to induce obesity and had similar increases in body weight and body fat. This was accompanied by increased hepatic triglyceride but no differences in hepatic glutathione levels compared with mice fed chow. However, Cbs(+/-) mice with diet-induced obesity had greater glucose intolerance and lower total and reduced glutathione levels in the heart, accompanied by lower plasma cysteine levels compared with Cbs(+/+) mice. Higher triglyceride concentrations, increased oxidative stress, and increased markers of apoptosis were also observed in heart from Cbs(+/-) mice with diet-induced obesity compared with Cbs(+/+) mice. This study suggests a novel role for Cbs in maintaining the cardiac glutathione pool and protecting against cardiac lipid accumulation and oxidative stress during diet-induced obesity in mice.

  12. Diet-Induced Thermogenesis in Insects: A Developing Concept in Nutritional Ecology

    Science.gov (United States)

    Terry M. Trier; William J. Mattson

    2003-01-01

    Diet-induced thermogenesis (DIT) is a concept that has been well known in one form or another for more than a century in vertebrate nutrition and physiological ecology. Yet, it is practically unknown in the physiology and nutritional ecology of insects. We suggest that DIT is a ubiquitous mechanism occurring in most if not all organisms and functions to maintain...

  13. Low sodium diet and pregnancy-induced hypertension: a multi-centre randomised controlled trial

    NARCIS (Netherlands)

    Knuist, M.; Bonsel, G. J.; Zondervan, H. A.; Treffers, P. E.

    1998-01-01

    To examine the effectiveness of the standard policy in the Netherlands to prescribe a sodium restricted diet to prevent or to treat mild pregnancy-induced hypertension. Multi-centre randomised controlled trial between April 1992 and April 1994. Seven practices of independent midwives and one

  14. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

    Directory of Open Access Journals (Sweden)

    Heera Ram

    2014-01-01

    Full Text Available Acacia senegal L. (Fabaceae seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil for 15 days. Circulating total cholesterol (TC, HDL-cholesterol (HDL-C, LDL-cholesterol (LDL-C, triglycerides, and VLDL-cholesterol (VLDL-C levels; atherogenic index (AI; cardiac lipid peroxidation (LPO; planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34±0.72 and increased lumen volume (51.65±3.66, administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o. for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.

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

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    Beasley Joe

    2003-06-01

    Full Text Available 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 would be useful to treat these forms of obesity. We hypothesized that adrenalectomy would increase hypothalamic POMC mRNA and reverse obese phenotypes in obesity due to a high-fat diet as it does in obesity due to leptin deficiency. Results Retired breeder male mice were placed on a high-fat diet or a low-fat diet for two weeks, then adrenalectomized or sham-adrenalectomized. The high-fat diet increased body weight, adiposity, and plasma leptin, led to impaired glucose tolerance, and slightly stimulated hypothalamic proopiomelanocortin (POMC expression. Adrenalectomy of mice on the high-fat diet significantly reduced plasma corticosterone and strikingly increased both pituitary and hypothalamic POMC mRNA, but failed to reduce body weight, adiposity or leptin, although slight improvements in glucose tolerance and metabolic rate were observed. Conclusion These data suggest that neither reduction of plasma glucocorticoid levels nor elevation of hypothalamic POMC expression is effective to significantly reverse diet-induced obesity.

  16. Moringa oleifera-based diet protects against nickel-induced hepatotoxicity in rats

    Science.gov (United States)

    Stephen Adeyemi, Oluyomi; Sokolayemji Aroge, Cincin; Adewumi Akanji, Musbau

    2017-01-01

    Multiple health-promoting effects have been attributed to the consumption of Moringa oleifera leaves, as part of diet without adequate scientific credence. This study evaluated the effect of M. oleifera-based diets on nickel (Ni) - induced hepatotoxicity in rats. Male rats assigned into six groups were given oral administration of 20 mg/kg body weight nickel sulfate in normal saline and either fed normal diet orM. oleifera-based diets for 21 days. All animals were sacrificed under anesthesia 24 hours after the last treatment. Ni exposure elevated the rat plasma activities of alanine transaminase, aspartate transaminase and alkaline phosphatase significantly. Ni exposure also raised the levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol while depleting the high-density lipoprotein cholesterol concentration. Further, Ni exposure raised rat plasma malondialdehyde but depleted reduced glutathione concentrations. The histopathological presentations revealed inflammation and cellular degeneration caused by Ni exposure. We show evidence thatM. oleifera-based diets protected against Ni-induced hepatotoxicity by improving the rat liver function indices, lipid profile as well as restoring cellular architecture and integrity. Study lends credence to the health-promoting value ofM. oleifera as well as underscores its potential to attenuate hepatic injury. PMID:28808207

  17. High folic acid diet enhances tumour growth in PyMT-induced breast cancer.

    Science.gov (United States)

    Hansen, Mariann Fagernæs; Jensen, Sarah Østrup; Füchtbauer, Ernst-Martin; Martensen, Pia M

    2017-03-14

    The B-vitamin folate is among the most studied bioactive food compound, and a dietary intake meeting the daily requirements has been found to reduce the risk of cancer and cardiovascular diseases as well as preventing neural tube defects during fetal development. Several countries have therefore introduced dietary fortification with folic acid. However, clinical and animal studies suggest that folic acid has a dual role in cancer development. During the period of initial tumour progression, MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice were fed with normal diet and high folic acid diet. We found that PyMT-induced breast tumours highly express the cancer-specific folate receptor (FR), a feature they share with several human epithelial cancers in which expression of FRα correlates with tumour grade. Mice receiving a high folic acid diet displayed a significantly increased tumour volume compared with mice receiving normal diet. In the largest tumours, only found in mice on high folic acid diet, STAT3 was activated. In primary cells from PyMT tumours, STAT3 was activated upon treatment with folic acid in culture. Our results offer a novel molecular explanation for folic acid-induced growth of existing tumours.

  18. Diet-Induced Obesity and Its Differential Impact on Periodontal Bone Loss.

    Science.gov (United States)

    Muluke, M; Gold, T; Kiefhaber, K; Al-Sahli, A; Celenti, R; Jiang, H; Cremers, S; Van Dyke, T; Schulze-Späte, U

    2016-02-01

    Obesity is associated with abnormal lipid metabolism and impaired bone homeostasis. The aim of our study was to investigate the impact of specific elevated fatty acid (FA) levels on alveolar bone loss in a Porphyromonas gingivalis-induced model of periodontal disease and to analyze underlying cellular mechanisms in bone-resorbing osteoclasts and bone-forming osteoblasts in mice. Four-week-old male C57BL/6 mice were randomly divided in groups and subjected to a palmitic acid (PA)- or oleic acid (OA)-enriched high-fat diet (HFD) (20% of calories from FA) or a normal caloric diet (C group) (10% of calories from FA) for 16 wk. Starting at week 10, mice were infected orally with P. gingivalis (W50) or placebo to induce alveolar bone loss. Animals were sacrificed, and percentage fat, serum inflammation (tumor necrosis factor [TNF]-α), and bone metabolism (osteocalcin [OC], carboxy-terminal collagen crosslinks [CTX], and N-terminal propeptides of type I procollagen [P1NP]) markers were measured. Osteoblasts and osteoclasts were cultured in the presence of elevated PA or OA levels and exposed to P. gingivalis. Animals on FA-enriched diets weighed significantly more compared with animals on a normal caloric diet (P diet rather than weight gain and obesity alone modulates bone metabolism and can therefore influence alveolar bone loss. © International & American Associations for Dental Research 2015.

  19. Protective Effects of Pyridoxamine Supplementation in the Early Stages of Diet-Induced Kidney Dysfunction

    Directory of Open Access Journals (Sweden)

    F. Chiazza

    2017-01-01

    Full Text Available Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD or a diet enriched in fat and fructose (HD for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin. Kidney morphology of HD fed mice showed strong vacuolar degeneration and loss of tubule brush border, associated with a drastic increase in both advanced glycation end products (AGEs and AGEs receptor (RAGE. These effects were significantly counteracted by pyridoxamine, with consequent reduction of the diet-induced overactivation of NF-kB and Rho/ROCK pathways. Overall, the present study demonstrates for the first time that the administration of the antiglycative compound pyridoxamine can reduce the early stages of diet-dependent kidney injury and dysfunction by interfering at many levels with the profibrotic signaling and inflammatory cascades.

  20. Evaluation of the effect of soybean diet on interferon-α-induced depression in male mice

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    Yazdan Azimi Fashi

    2017-08-01

    Full Text Available Objective: Interferon-α (IFN therapy can cause depressive symptom which may lead to drug discontinuation. By interfering with tryptophan pathway, the available level of tryptophan required for serotonin synthesis decreases which could be related to depression. The aim of this study was to evaluate whether soybean diet could improve IFN-induced depression. Materials and Methods: Male mice weighing 28±3 g were used in the forced swimming test (FST as an animal model of depression; also, locomotor activity was recorded. IFN 16×105 IU/kg was injected subcutaneously for 6 days. Animals were fed with regular diet or soybean diet at 3 concentrations throughout the experiment. Fluoxetine was the reference drug. To check whether the tryptophan content in the soy bean diet was effective, a group of animals was injected with a single dose of tryptophan on the test day. Results: IFN-α increased the immobility time in the FST (192 sec ± 5.4, that denotes depression in mice. Soybean diets caused less immobility that was more profound with 50% soybean (26.4 sec ± 6. This diet overcame the depression caused by IFN in the FST (54 sec±18. This result was parallel with that of tryptophan injected to animals (38 sec±17. All the animals showed normal locomotor activity. Conclusion: For the first time, we showed that soybean diet could counteract with depression caused by IFN-α. Since tryptophan therapy had similar effects, possibly the tryptophan content of soybean had induced the serotonin synthesis. Thus, not only less harmful kynurenine was produced but also more serotonin was available in the brain to overcome depression. However, this interpretation needs further evaluations.

  1. Inhibition of soluble epoxide hydrolase attenuates high-fat-diet-induced hepatic steatosis by reduced systemic inflammatory status in mice.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    Full Text Available Non-alcoholic fatty liver disease is associated with obesity and considered an inflammatory disease. Soluble epoxide hydrolase (sEH is a major enzyme hydrolyzing epoxyeicosatrienoic acids and attenuates their cardiovascular protective and anti-inflammatory effects. We examined whether sEH inhibition can protect against high-fat (HF-diet-induced fatty liver in mice and the underlying mechanism. Compared with wild-type littermates, sEH-null mice showed lower diet-induced lipid accumulation in liver, as seen by Oil-red O staining and triglycerides levels. We studied the effect of sEH inhibition on diet-induced fatty liver by feeding C57BL/6 mice an HF diet for 8 weeks (short-term or 16 weeks (long-term and administering t-AUCB, a selective sEH inhibitor. sEH inhibition had no effect on the HF-diet-increased body and adipose tissue weight or impaired glucose tolerance but alleviated the diet-induced hepatic steatosis. Adenovirus-mediated overexpression of sEH in liver increased the level of triglycerides in liver and the hepatic inflammatory response. Surprisingly, the induced expression of sEH in liver occurred only with the long-term but not short-term HF diet, which suggests a secondary effect of HF diet on regulating sEH expression. Furthermore, sEH inhibition attenuated the HF-diet-induced increase in plasma levels of proinflammatory cytokines and their mRNA upregulation in adipose tissue, which was accompanied by increased macrophage infiltration. Therefore, sEH inhibition could alleviate HF-diet-induced hepatic steatosis, which might involve its anti-inflammatory effect in adipose tissue and direct inhibition in liver. sEH may be a therapeutic target for HF-diet-induced hepatic steatosis in inhibiting systemic inflammation.

  2. Is Western Diet-Induced Nonalcoholic Steatohepatitis in Ldlr-/- Mice Reversible?

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    Kelli A Lytle

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a major public health burden in western societies. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH, is characterized by hepatosteatosis, inflammation, oxidative stress, and hepatic damage that can progress to fibrosis and cirrhosis; risk factors for hepatocellular carcinoma. Given the scope of NASH, validating treatment protocols (i.e., low fat diets and weight loss is imperative.We evaluated the efficacy of two diets, a non-purified chow (NP and purified (low-fat low-cholesterol, LFLC diet to reverse western diet (WD-induced NASH and fibrosis in Ldlr-/- mice.Mice fed WD for 22-24 weeks developed robust hepatosteatosis with mild fibrosis, while mice maintained on the WD an additional 7-8 weeks developed NASH with moderate fibrosis. Returning WD-fed mice to the NP or LFLC diets significantly reduced body weight and plasma markers of metabolic syndrome (dyslipidemia, hyperglycemia and hepatic gene expression markers of inflammation (Mcp1, oxidative stress (Nox2, fibrosis (Col1A, LoxL2, Timp1 and collagen crosslinking (hydroxyproline. Time course analyses established that plasma triglycerides and hepatic Col1A1 mRNA were rapidly reduced following the switch from the WD to the LFLC diet. However, hepatic triglyceride content and fibrosis did not return to normal levels 8 weeks after the change to the LFLC diet. Time course studies further revealed a strong association (r2 ≥ 0.52 between plasma markers of inflammation (TLR2 activators and hepatic fibrosis markers (Col1A, Timp1, LoxL2. Inflammation and fibrosis markers were inversely associated (r2 ≥ 0.32 with diet-induced changes in hepatic ω3 and ω6 polyunsaturated fatty acids (PUFA content.These studies establish a temporal link between plasma markers of inflammation and hepatic PUFA and fibrosis. Low-fat low-cholesterol diets promote reversal of many, but not all, features associated with WD-induced NASH and fibrosis in Ldlr

  3. Stress-induced visceral analgesia assessed non-invasively in rats is enhanced by prebiotic diet

    Institute of Scientific and Technical Information of China (English)

    Muriel Larauche; Agata Mulak; Pu-Qing Yuan; Osamu Kanauchi; Yvette Taché

    2012-01-01

    AIM: To investigate the influence of repeated water avoidance stress (rWAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the modulation of the response by a prebiotic diet in rats using a novel surgery-free method of solid-state manometry.METHODS: Male Wistar rats fed a standard diet with or without 4% enzyme-treated rice fiber (ERF) for 5 wk were subjected to rWAS (1 h daily x 10 d) or no stress. The VMR to graded phasic CRD was assessed by intraluminal colonic pressure recording on days 0 (baseline), 1 and 10 (45 min) and 11 (24 h) after rWAS and expressed as percentage change from baseline. Cecal content of short chain fatty acids and distal colonic histology were assessed on day 11.RESULTS: WAS on day 1 reduced the VMR to CRD at 40 and 60 mmHg similarly by 28.9% ± 6.6% in both diet groups. On day 10, rWAS-induced reduction of VMR occurred only at 40 mmHg in the standard diet group (36.2% ± 17.8%) while in the ERF group VMR was lowered at 20, 40 and 60 mmHg by 64.9% ± 20.9%, 49.3% ± 11.6% and 38.9% ± 7.3% respectively. The visceral analgesia was still observed on day 11 in ERF- but not in standard diet-fed rats. By contrast the non-stressed groups (standard or ERF diet) exhibited no changes in VMR to CRD. In standard diet-fed rats, rWAS induced mild colonic histological changes that were absent in ERF-fed rats exposed to stress compared to non-stressed rats. The reduction of cecal content of isobutyrate and total butyrate, but not butyrate alone, was correlated with lower visceral pain response. Additionally, ERF diet increased rWAS-induced defecation by 26% and 75% during the first 0-15 min and last 15-60 min, respectively, compared to standard diet, and reduced rats' body weight gain by 1.3 fold independently of their stress status. CONCLUSION: These data provide the first evidence of psychological stress-related visceral analgesia in rats that was enhanced by chronic intake of ERF prebiotic.

  4. ATF7 ablation prevents diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Liu, Yang; Maekawa, Toshio; Yoshida, Keisuke; Furuse, Tamio; Kaneda, Hideki; Wakana, Shigeharu; Ishii, Shunsuke

    2016-09-16

    The activating transcription factor (ATF)2 family of transcription factors regulates a variety of metabolic processes, including adipogenesis and adaptive thermogenesis. ATF7 is a member of the ATF2 family, and mediates epigenetic changes induced by environmental stresses, such as social isolation and pathogen infection. However, the metabolic role of ATF7 remains unknown. The aim of the present study is to examine the role of ATF7 in metabolism using ATF7-dificeint mice. Atf7(-/-) mice exhibited lower body weight and resisted diet-induced obesity. Serum triglycerides, resistin, and adipose tissue mass were all significantly lower in ATF7-deficient mice. Fasting glucose levels and glucose tolerance were unaltered, but systemic insulin sensitivity was increased, by ablation of ATF7. Indirect calorimetry revealed that oxygen consumption by Atf7(-/-) mice was comparable to that of wild-type littermates on a standard chow diet, but increased energy expenditure was observed in Atf7(-/-) mice on a high-fat diet. Hence, ATF7 ablation may impair the development and function of adipose tissue and result in elevated energy expenditure in response to high-fat-feeding obesity and insulin resistance, indicating that ATF7 is a potential therapeutic target for diet-induced obesity and insulin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Effects of maternal linseed oil supplementation on oxidative stress markers in cafeteria diet induced obese rats

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    Hafida Merzouk

    2015-07-01

    Full Text Available We investigated the role of dietary linseed oil in the modulation of biochemical parameters and oxidant/antioxidant markers in cafeteria-induced obese rats and their offspring. Female wistar rats were fed on control or cafeteria diet, supplemented or not with linseed oil (5% for one month before and during the gestation. At parturition, the mothers and their offspring were killed. Weight gain, food intake, serum biochemical and oxidant/antioxidant markers were determined. Cafeteria diet induced a significant increase in body weight, food intake and adverse alterations in biochemical parameters such as an increase in serum glucose, triglyceride, cholesterol and oxidant markers. Linseed oil supplementation induced a reduction in weight gain, serum lipids and a modulation of oxidative stress, improving metabolic status. In conclusions, linseed oil displayed remarkable health benefits by decreasing plasma and oxidant/antioxidant markers in both obese mothers and their newborns.

  6. Diet-induced impulsivity: Effects of a high-fat and a high-sugar diet on impulsive choice in rats.

    Science.gov (United States)

    Steele, Catherine C; Pirkle, Jesseca R A; Kirkpatrick, Kimberly

    2017-01-01

    Impulsive choice is a common charactertistic among individuals with gambling problems, obesity, and substance abuse issues. Impulsive choice has been classified as a trans-disease process, and understanding the etiology of trait impulsivity could help to understand how diseases and disorders related to impulsive choice are manifested. The Western diet is a possible catalyst of impulsive choice as individuals who are obese and who eat diets high in fat and sugar are typically more impulsive. However, such correlational evidence is unable to discern the direction and causal nature of the relationship. The present study sought to determine how diet may directly contribute to impulsive choice. After 8 weeks of dietary exposure (high-fat, high-sugar, chow), the rats were tested on an impulsive choice task, which presented choices between a smaller-sooner reward (SS) and a larger-later reward (LL). Then, the rats were transferred to a chow diet and retested on the impulsive choice task. The high-sugar and high-fat groups made significantly more impulsive choices than the chow group. Both groups became more self-controlled when they were off the diet, but there were some residual effects of the diet on choice behavior. These results suggest that diet, specifically one high in processed fat or sugar, induces impulsive choice. This diet-induced impulsivity could be a precursor to other disorders that are characterized by impulsivity, such as diet-induced obesity, and could offer potential understanding of the trans-disease nature of impulsive choice.

  7. Milk diets influence doxorubicin-induced intestinal toxicity in piglets

    DEFF Research Database (Denmark)

    Shen, R. L.; Pontoppidan, P. E.; Rathe, M.

    2016-01-01

    with doxorubicin (DOX) treatment. Five-day-old pigs were administered DOX (1 × 100 mg/m(2)) or an equivalent volume of saline (SAL) and either fed formula (DOX-Form, n = 9, or SAL-Form, n = 7) or bovine colostrum (DOX-Colos, n = 9, or SAL-Colos, n = 7). Pigs were euthanized 5 days after initiation of chemotherapy...... IL-8 levels compared with DOX-Form (all P single dose of DOX induces intestinal toxicity in preweaned pigs...

  8. Effects of vitamin D on insulin resistance and myosteatosis in diet-induced obese mice.

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    Elisa Benetti

    Full Text Available Epidemiological studies pointed out to a strong association between vitamin D deficiency and type 2 diabetes prevalence. However, the role of vitamin D supplementation in the skeletal muscle, a tissue that play a crucial role in the maintenance of glucose homeostasis, has been scarcely investigated so far. On this basis, this study aimed to evaluate the effect of vitamin D supplementation in a murine model of diet-induced insulin resistance with particular attention to the effects evoked on the skeletal muscle. Male C57BL/6J mice (n = 40 were fed with a control or a High Fat-High Sugar (HFHS diet for 4 months. Subsets of animals were treated for 2 months with vitamin D (7 μg·kg-1, i.p. three times/week. HFHS diet induced body weight increase, hyperglycemia and impaired glucose tolerance. HFHS animals showed an impaired insulin signaling and a marked fat accumulation in the skeletal muscle. Vitamin D reduced body weight and improved systemic glucose tolerance. In addition, vitamin D restored the impaired muscle insulin signaling and reverted myosteatosis evoked by the diet. These effects were associated to decreased activation of NF-κB and lower levels of TNF-alpha. Consistently, a significantly decreased activation of the SCAP/SREBP lipogenic pathway and lower levels of CML protein adducts and RAGE expression were observed in skeletal muscle of animals treated with vitamin D. Collectively, these data indicate that vitamin D-induced selective inhibition of signaling pathways (including NF-κB, SCAP/SREBP and CML/RAGE cascades within the skeletal muscle significantly contributed to the beneficial effects of vitamin D supplementation against diet-induced metabolic derangements.

  9. [The effects of high-protein, low-carbohydrate diet on body weight and the expression of gastrointestinal hormones in diet-induced obesity rat].

    Science.gov (United States)

    Chen, Hai-yan; Ma, Li-chuan; Li, Yin-yin; Zhao, Jia-jun; Li, Ming-long

    2011-02-01

    To investigate the effects of long-term high-protein, low-carbohydrate diet on body weight and the expression of gastrointestinal hormones in diet-induced obesity rats. Twenty-four diet-induced obesity rat models were established by feeding fat-enriched diet, then were randomly divided into two groups by stratified sampling method by weight: the high-protein diet group (HP, 36.7% of energy from protein), and the normal chow group (NC, 22.4% of energy from protein), 12 rats in each group. The total calorie intake of each rat per day was similar and was maintained for 24 weeks, then body weight, visceral fat mass, fasting plasma ghrelin and glucagon-like peptide-1 (GLP-1) were determined, as well as protein expression of ghrelin in stomach, GLP-1 in ileum were detected by immunohistochemistry. After 24 weeks, body weight of HP, NC groups were (490.92 ± 39.47) g and (545.55 ± 31.08) g, respectively (t = -3.664, P 0.05), and plasma ghrelin level was negatively correlated to body weight (r = -0.370, t = -1.899, P body weight and visceral fat, increase the expression of ghrelin, and decline GLP-1 expression in diet-induced obesity rats.

  10. Antibody-Directed Glucocorticoid Targeting to CD163 in M2-type Macrophages Attenuates Fructose-Induced Liver Inflammatory Changes

    DEFF Research Database (Denmark)

    Svendsen, Pia; Graversen, Jonas Heilskov; Etzerodt, Anders

    2017-01-01

    Increased consumption of high-caloric carbohydrates contributes substantially to endemic non-alcoholic fatty liver disease in humans, covering a histological spectrum from fatty liver to steatohepatitis. Hypercaloric intake and lipogenetic effects of fructose and endotoxin-driven activation...... of liver macrophages are suggested to be essential to disease progression. In the present study, we show that a low dose of an anti-CD163-IgG-dexamethasone conjugate targeting the hemoglobin scavenger receptor CD163 in Kupffer cells and other M2-type macrophages has a profound effect on liver inflammatory...... changes in rats on a high-fructose diet. The diet induced severe non-alcoholic steatohepatitis (NASH)-like changes within a few weeks but the antibody-drug conjugate strongly reduced inflammation, hepatocyte ballooning, fibrosis, and glycogen deposition. Non-conjugated dexamethasone or dexamethasone...

  11. Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Éder Marcolin

    2011-03-01

    Full Text Available CONTEXT: Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied. OBJECTIVES: This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder. METHODS: Thirty male C57BL6 mice divided in two groups (n = 15 were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5%. RESULTS: The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100% of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity. CONCLUSION: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in

  12. Fluoride Intensifies Hypercaloric Diet-Induced ER Oxidative Stress and Alters Lipid Metabolism.

    Directory of Open Access Journals (Sweden)

    Heloisa Aparecida Barbosa Silva Pereira

    Full Text Available Here, we evaluated the relationship of diet and F-induced oxidative stress to lipid metabolism in the liver of rats eating normocaloric or hypercaloric diets for two time periods (20 or 60 days.Seventy-two 21-day-old Wistar rats were divided into 2 groups (n = 36 based on the type of diet they were eating; each of these groups was then further divided into another two groups (n = 18 based on the time periods of either 20 or 60 days, for a total of four groups. Each of these was divided into 3 subgroups (n = 6 animals/subgroup, dependent on the dose of F administered in the drinking water (0 mg/L(control, 15 mg/L or 50 mg/L. After the experimental period, blood samples and the liver were collected. Plasma samples were analyzed for HDL, cholesterol and triglycerides. Western blots were performed to probe for GRP78, Erp29, SOD2, Apo-E and SREBP in hepatic tissues.As expected,the expression of target proteins involved in oxidative stress increased in the F-treated groups, especially in liver tissue obtained from animals eating a hypercaloric diet. Most changes in the lipid levels and pathological conditions were seen earlier in the time period, at day 20. The morphometric analyses showed a reduction in steatosis in groups on ahypercaloric diet and treated with 50 mg F/L compared to the control, while no changes were obtained in normocaloric-fed rats. Accordingly, plasma TG was reduced in the F-treated group. The reduced expression of Apo-E in a time- and diet-dependent pattern may account for the particular decrease in steatosis in hypercaloric-fed F-treated rats.These results suggest that F changes liver lipid homeostasis, possibly because of the induction of oxidative stress, which seems to be higher in animals fed hypercaloric diets.

  13. Stress- and diet-induced fat gain is controlled by NPY in catecholaminergic neurons

    Science.gov (United States)

    Zhang, Lei; Lee, I-Chieh J.; Enriquez, Rondaldo F.; Lau, Jackie; Vähätalo, Laura H.; Baldock, Paul A.; Savontaus, Eriika; Herzog, Herbert

    2014-01-01

    Neuropeptide Y (NPY) and noradrenaline are commonly co-expressed in sympathetic neurons. Both are key regulators of energy homeostasis and critical for stress-coping. However, little is known about the specific function of NPY in the catecholaminergic system in these regulations. Here we show that mice with NPY expression only in the noradrenergic and adrenergic cells of the catecholaminergic system (catNPY) exhibited exacerbated diet-induced obesity, lower body and brown adipose tissue temperatures compared to WT and NPY−/− mice under a HFD. Furthermore, chronic stress increased adiposity and serum corticosterone level in WT but not NPY−/− mice. Re-introducing NPY specifically to the catecholaminergic system in catNPY mice restored stress responsiveness associated with increased respiratory exchange ratio and decreased liver pACC to tACC ratio. These results demonstrate catecholaminergic NPY signalling is critical in mediating diet- and chronic stress-induced fat gain via effects on diet-induced thermogenesis and stress-induced increases in corticosterone levels and lipogenic capacity. PMID:25061562

  14. Calpain Inhibition Attenuates Adipose Tissue Inflammation and Fibrosis in Diet-induced Obese Mice.

    Science.gov (United States)

    Muniappan, Latha; Javidan, Aida; Jiang, Weihua; Mohammadmoradi, Shayan; Moorleghen, Jessica J; Katz, Wendy S; Balakrishnan, Anju; Howatt, Deborah A; Subramanian, Venkateswaran

    2017-10-31

    Adipose tissue macrophages have been proposed as a link between obesity and insulin resistance. However, the mechanisms underlying these processes are not completely defined. Calpains are calcium-dependent neutral cysteine proteases that modulate cellular function and have been implicated in various inflammatory diseases. To define whether activated calpains influence diet-induced obesity and adipose tissue macrophage accumulation, mice that were either wild type (WT) or overexpressing calpastatin (CAST Tg), the endogenous inhibitor of calpains were fed with high (60% kcal) fat diet for 16 weeks. CAST overexpression did not influence high fat diet-induced body weight and fat mass gain throughout the study. Calpain inhibition showed a transient improvement in glucose tolerance at 5 weeks of HFD whereas it lost this effect on glucose and insulin tolerance at 16 weeks HFD in obese mice. However, CAST overexpression significantly reduced adipocyte apoptosis, adipose tissue collagen and macrophage accumulation as detected by TUNEL, Picro Sirius and F4/80 immunostaining, respectively. CAST overexpression significantly attenuated obesity-induced inflammatory responses in adipose tissue. Furthermore, calpain inhibition suppressed macrophage migration to adipose tissue in vitro. The present study demonstrates a pivotal role for calpains in mediating HFD-induced adipose tissue remodeling by influencing multiple functions including apoptosis, fibrosis and inflammation.

  15. β-Cryptoxanthin alleviates diet-induced nonalcoholic steatohepatitis by suppressing inflammatory gene expression in mice.

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    Masuko Kobori

    Full Text Available Recent nutritional epidemiological surveys showed that serum β-cryptoxanthin inversely associates with the risks for insulin resistance and liver dysfunction. Consumption of β-cryptoxanthin possibly prevents nonalcoholic steatohepatitis (NASH, which is suggested to be caused by insulin resistance and oxidative stress from nonalcoholic fatty liver disease. To evaluate the effect of β-cryptoxanthin on diet-induced NASH, we fed a high-cholesterol and high-fat diet (CL diet with or without 0.003% β-cryptoxanthin to C56BL/6J mice for 12 weeks. After feeding, β-cryptoxanthin attenuated fat accumulation, increases in Kupffer and activated stellate cells, and fibrosis in CL diet-induced NASH in the mice. Comprehensive gene expression analysis showed that although β-cryptoxanthin histochemically reduced steatosis, it was more effective in inhibiting inflammatory gene expression change in NASH. β-Cryptoxanthin reduced the alteration of expression of genes associated with cell death, inflammatory responses, infiltration and activation of macrophages and other leukocytes, quantity of T cells, and free radical scavenging. However, it showed little effect on the expression of genes related to cholesterol and other lipid metabolism. The expression of markers of M1 and M2 macrophages, T helper cells, and cytotoxic T cells was significantly induced in NASH and reduced by β-cryptoxanthin. β-Cryptoxanthin suppressed the expression of lipopolysaccharide (LPS-inducible and/or TNFα-inducible genes in NASH. Increased levels of the oxidative stress marker thiobarbituric acid reactive substances (TBARS were reduced by β-cryptoxanthin in NASH. Thus, β-cryptoxanthin suppresses inflammation and the resulting fibrosis probably by primarily suppressing the increase and activation of macrophages and other immune cells. Reducing oxidative stress is likely to be a major mechanism of inflammation and injury suppression in the livers of mice with NASH.

  16. Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought.

    Science.gov (United States)

    Kozijn, A E; Gierman, L M; van der Ham, F; Mulder, P; Morrison, M C; Kühnast, S; van der Heijden, R A; Stavro, P M; van Koppen, A; Pieterman, E J; van den Hoek, A M; Kleemann, R; Princen, H M G; Mastbergen, S C; Lafeber, F P J G; Zuurmond, A-M; Bobeldijk, I; Weinans, H; Stoop, R

    2018-01-01

    Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr -/- . Leiden and ApoE*3Leiden.CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls. Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr -/- . Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender. Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were identified as important contributing factors. Copyright © 2017. Published by Elsevier Ltd.

  17. 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.

  18. Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

    Science.gov (United States)

    Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

    2002-01-01

    Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

  19. Diet-Induced Obesity and the Mechanism of Leptin Resistance.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    Leptin signaling blockade by chronic overstimulation of the leptin receptor or hypothalamic pro-inflammatory responses due to elevated levels of saturated fatty acid can induce leptin resistance by activating negative feedback pathways. Although, long form leptin receptor (Ob-Rb) initiates leptin signaling through more than seven different signal transduction pathways, excessive suppressor of cytokine signaling-3 (SOCS-3) activity is a potential mechanism for the leptin resistance that characterizes human obesity. Because the leptin-responsive metabolic pathways broadly integrate with other neurons to control energy balance, the methods used to counteract the leptin resistance has extremely limited effect. In this chapter, besides the impairment of central and peripheral leptin signaling pathways, limited access of leptin to central nervous system (CNS) through blood-brain barrier, mismatch between high leptin and the amount of leptin receptor expression, contradictory effects of cellular and circulating molecules on leptin signaling, the connection between leptin signaling and endoplasmic reticulum (ER) stress and self-regulation of leptin signaling has been discussed in terms of leptin resistance.

  20. Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model.

    Science.gov (United States)

    Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B; Isales, Carlos; Caldwell, R William; Fulzele, Sadanand

    2016-02-15

    A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of l-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of l-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases. Published by Elsevier Ireland Ltd.

  1. Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

    Science.gov (United States)

    Martin, Gregory G; Landrock, Danilo; Chung, Sarah; Dangott, Lawrence J; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

    2017-01-01

    The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. © 2016 International Society for Neurochemistry.

  2. A Mouse Model of Erectile Dysfunction Via Diet-Induced Diabetes Mellitus

    Science.gov (United States)

    Xie, Donghua; Odronic, Shelley I.; Wu, Feihua; Pippen, Anne; Donatucci, Craig F.; Annex, Brian H.

    2007-01-01

    Objective Diabetes mellitus (DM) is a significant risk factor in the development of erectile dysfunction (ED). We sought to determine whether diet induced DM in mice would recapitulate the major features of human ED. Methods In total, 150 C57BL6 (bl-6) mice were divided into 6 groups (n=25/group). One hundred twenty five were fed a high fat (45% total calories) diet for the final 4 (Group 2), 8 (Group 3), 12 (Group 4),16 (Group 5), or 22 (Group 6) weeks. Group 1 was fed a normal diet. Mice were 22-25 weeks old at study termination. Corporal tissues were harvested and studied for a) endothelium-dependent and endothelium-independent vasoreactivity, b) endothelial and smooth muscle cell content by immunohistochemistry, c) NOS expression by NADPH-diaphorase staining. d) Apoptosis by TUNEL staining. Results Blood glucoses were greater in Groups 2 -6 vs. Group 1. Vasoreactivities, endothelial cell content, smooth muscle/collagen ratio were lower while apoptosis was higher in the DM mice (p=0.0001, p=0.10, p=0.0002, pCorporal tissue from mice with diet induced DM demonstrate many of the major functional, structural, and biochemical changes found in humans with ED. This model should serve as a valuable tool for advancing our understanding the role DM plays in the pathogenesis of ED. PMID:17656247

  3. Mouse model of erectile dysfunction due to diet-induced diabetes mellitus.

    Science.gov (United States)

    Xie, Donghua; Odronic, Shelley I; Wu, Feihua; Pippen, Anne; Donatucci, Craig F; Annex, Brian H

    2007-07-01

    To determine whether diet-induced diabetes mellitus (DM) in mice would reproduce the major features of human erectile dysfunction (ED) because DM is a significant risk factor in the development of ED. In total, 150 C57BL6 (bl6) mice were divided into six groups of 25 mice each. Of these 150 mice, 125 were fed a high-fat (45% of total calories) diet for the final 4 (group 2), 8 (group 3), 12 (group 4), 16 (group 5), or 22 (group 6) weeks. Group 1 was fed a normal diet. The mice were 22 to 25 weeks old at study termination. The corporal tissues were harvested and studied for endothelium-dependent and endothelium-independent vasoreactivity, endothelial and smooth muscle cell content by immunohistochemistry, nitric oxide synthase expression by nicotinamide adenine dinucleotide-diaphorase staining, and apoptosis by terminal deoxynucleotidyl transferase biotin-D-UTP nick-end labeling staining. The blood glucose levels were greater in groups 2 to 6 compared with those in group 1. The vasoreactivity, endothelial cell content, and smooth muscle/collagen ratio were lower and apoptosis were greater in the DM mice (P = 0.0001, P = 0.10, P = 0.0002, P Corporal tissue from mice with diet-induced DM demonstrated many of the major functional, structural, and biochemical changes found in humans with ED. This model should serve as a valuable tool for advancing our understanding of the role DM plays in the pathogenesis of ED.

  4. 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.

  5. Helicobacter pylori Infection Aggravates Diet-induced Insulin Resistance in Association With Gut Microbiota of Mice.

    Science.gov (United States)

    He, Cong; Yang, Zhen; Cheng, Dandan; Xie, Chuan; Zhu, Yin; Ge, Zhongming; Luo, Zhijun; Lu, Nonghua

    2016-10-01

    Emerging evidence suggests that Helicobacter pylori infection is associated with insulin resistance (IR) yet the underlying mechanisms are still obscure. The vital role of gut microbiota in triggering IR has been increasingly reported, however, no study has explored the correlation of gut microbiota and H. pylori-associated IR. Using H. pylori-infected mice model fed different diet structures, we demonstrated that H. pylori infection significantly aggravated high-fat diet (HFD)-induced metabolic disorders at the early stage, the extent of which was close to the effect of long-term HFD. Interestingly, we observed dynamic alterations in gut microbiota that were consistent with the changes in the metabolic phenotype induced by H. pylori and HFD. There may be an interaction among H. pylori, diet and gut microbiota, which dysregulates the host metabolic homeostasis, and treatment of H. pylori may be beneficial to the patients with impaired glucose tolerance in addition to diet control. Copyright © 2016. Published by Elsevier B.V.

  6. Development of a Murine Model of Early Sepsis in Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Momina Khan

    2014-01-01

    Full Text Available Sepsis, a global health issue, is the most common cause of mortality in the intensive care unit. The aim of this study was to develop a new model of sepsis that investigates the impact of prolonged western diet (WD induced obesity on the response to early sepsis. Male C57BL/6 mice were fed either a high fat WD or normal chow diet (NCD for 6, 15, or 27 weeks. Septic obese mice at 15 and 27 weeks had significantly lower levels of lung myeloperoxidase (26.3 ± 3.80 U/mg tissue compared to age matched ad lib (44.1 ± 2.86 U/mg tissue and diet restricted (63.2 ± 5.60 U/mg tissue controls. Low levels of lung inflammation were not associated with changes in hepatic cytokines and oxidative stress levels. Obese mice had significantly (P<0.0001 larger livers compared to controls. Histological examination of the livers demonstrated that WD fed mice had increased inflammation with pronounced fat infiltration, steatosis, and hepatocyte ballooning. Using this model of prolonged exposure to high fat diet we have data that agree with recent clinical observations suggesting obese individuals are protected from sepsis-induced lung injury. This model will allow us to investigate the links between damage to the hepatic microcirculation, immune response, and lung injury.

  7. Diet-induced changes in hypothalamic pro-opio-melanocortin mRNA in the rat hypothalamus.

    Science.gov (United States)

    Torri, Carla; Pedrazzi, Patrizia; Leo, Giuseppina; Müller, Eugenio E; Cocchi, Daniela; Agnati, Luigi F; Zoli, Michele

    2002-06-01

    Hypothalamic mRNA and peptide levels of pro-opio-melanocortin (POMC) and other neuropeptides were studied in rats that either develop obesity (diet-induced obese, DIO), when fed a palatable and hypercaloric diet (cafeteria diet, caf) or do not develop obesity (diet resistant, DR), when fed the same diet. cafDIO rats showed a significant increase in POMC, but not in melanin concentrating hormone, mRNA levels as determined by semiquantitative in situ hybridization. cafDR and cafDIO rats showed no change in POMC-derived peptide levels, whereas neuropeptide Y immunoreactivity was significantly increased in cafDR rats. POMC mRNA levels were also studied in high-fat diet-fed rats but no significant change was observed. Altered hypothalamic transmission by POMC-derived peptides may contribute to the susceptibility of cafDIO rats to the weight promoting action of caf diet.

  8. The intake of high-fat diets induces an obesogenic-like gene expression profile in peripheral blood mononuclear cells, which is reverted by dieting.

    Science.gov (United States)

    Reynés, Bàrbara; García-Ruiz, Estefanía; Palou, Andreu; Oliver, Paula

    2016-06-01

    Peripheral blood mononuclear cells (PBMC) are increasingly used for nutrigenomic studies. In this study, we aimed to identify whether these cells could reflect the development of an obesogenic profile associated with the intake of high-fat (HF) diets. We analysed, by real-time RT-PCR, the dietary response of key genes related to lipid metabolism, obesity and inflammation in PBMC of control rats, rats fed a cafeteria or a commercial HF diet and rats fed a control diet after the intake of a cafeteria diet (post-cafeteria model). Cafeteria diet intake, which resulted in important overweight and related complications, altered the expressions of most of the studied genes in PBMC, evidencing the development of an obesogenic profile. Commercial HF diet, which produced metabolic alterations but in the absence of noticeably increased body weight, also altered PBMC gene expression, inducing a similar regulatory pattern as that observed for the cafeteria diet. Regulation of carnitine palmitoyltransferase I (Cpt1a) mRNA expression was of special interest; its expression reflected metabolic alterations related to the intake of both obesogenic diets (independently of increased body weight) even at an early stage as well as metabolic recovery in post-cafeteria animals. Thus, PBMC constitute an important source of biomarkers that reflect the increased adiposity and metabolic deregulation associated with the intake of HF diets. In particular, we propose an analysis of Cpt1a expression as a good biomarker to detect the early metabolic alterations caused by the consumption of hyperlipidic diets, and also as a marker of metabolic recovery associated to weight loss.

  9. Fructose diet and VEGF-induced plasma extravasation in hamster cheek pouch.

    Science.gov (United States)

    Félétou, Michel; Boulanger, Michelle; Staczek, Joanna; Broux, Olivier; Duhault, Jacques

    2003-03-01

    To determine in the hamster cheek pouch whether or not the changes in plasma extravasation induced by vascular endothelial growth factor (VEGF) could be affected by fructose diet. Hamsters were subjected to control drinking water or to water containing fructose (10 %) for 18 weeks. The fructose diet induced a small but significant increase in glycemia (0.80+/-0.11 and 1.09+/-0.15, n=8 and 9 for control and fructose- treated animals, respectively, Pdiet while the effects of VEGF were markedly increased (maximal number of leakage sites: 76+/-20 and 126+/-55, n = 8 and 9 for control and fructose-treated animals, respectively, P<0.01). Even moderate changes in glycemic levels can produce profound alteration in the VEGF response.

  10. 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

    BACKGROUND AND AIM: The neurotransmitter histamine is involved in the regulation of appetite and in the development of age-related obesity in mice. Furthermore, histamine is a mediator of the anorexigenic action of leptin. The aim of the present study was to investigate a possible role of histamine...... 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, plasma leptin......-KO mice compared to STD-fed HDC-KO mice was observed, while no such difference was observed in WT mice. CONCLUSION: Based on our results, we conclude that histamine plays a role in the development of HFD-induced obesity....

  11. 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...... 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...... by increased hepatic mitochondrial beta-oxidation and a decreased fatty acid/ketone body ratio in plasma. These findings indicate that PPARalpha-dependent mechanisms play a pivotal role, but additionally, the involvement of PPARalpha-independent pathways is conceivable. Taken together, our results suggest...

  12. Effects of Maternal Linseed Oil Supplementation on Metabolic Parameters in Cafeteria Diet-induced Obese Rats.

    Science.gov (United States)

    Benaissa, Nawel; Merzouk, Hafida; Merzouk, Sid Ahmed; Narce, Michel

    2015-04-01

    Because linseed oil may influence maternal and fetal metabolisms, we investigated its role in the modulation of lipid metabolism in cafeteria diet-induced obese rats and their offspring. Female Wistar rats were fed control or cafeteria food, which were either supplemented or not supplemented with linseed oil (5%) for 1 month before and during gestation. At parturition, serum and tissue lipids and enzyme activities were analyzed. Cafeteria diet induced adverse metabolic alterations in both mothers and offspring. Linseed oil improved metabolic status. In conclusion, linseed oil displayed health benefits by modulating tissue enzyme activities in both obese mothers and their newborns. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  13. Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice.

    Science.gov (United States)

    Li, Jibiao; Matye, David J; Wang, Yifeng; Li, Tiangang

    2017-04-01

    Sortilin 1 (Sort1) is a trafficking receptor that has been implicated in the regulation of plasma cholesterol in humans and mice. Here, we use metabolomics and hyperinsulinemic-euglycemic clamp approaches to obtain further understanding of the in vivo effects of Sort1 deletion on diet-induced obesity as well as on adipose lipid and glucose metabolism. Results show that Sort1 knockout (KO) does not affect Western diet-induced obesity nor adipose fatty acid and ceramide concentrations. Under the basal fasting state, chow-fed Sort1 KO mice have decreased adipose glycolytic metabolites, but Sort1 deletion does not affect insulin-stimulated tissue glucose uptake during the insulin clamp. These results suggest that Sort1 loss-of-function in vivo does not affect obesity development, but differentially modulates adipose glucose metabolism under fasting and insulin-stimulated states. © 2017 Federation of European Biochemical Societies.

  14. Diet-induced obesity regulates adipose-resident stromal cell quantity and extracellular matrix gene expression

    OpenAIRE

    Pincu, Yair; Huntsman, Heather D.; Zou, Kai; De Lisio, Michael; Ziad S. Mahmassani; Michael R. Munroe; Garg, Koyal; Jensen, Tor; Boppart, Marni D.

    2016-01-01

    Adipose tissue expansion during periods of excess nutrient intake requires significant turnover of the extracellular matrix (ECM) to allow for maximal lipid filling. Recent data suggest that stromal cells may be a primary contributor to ECM modifications in visceral adipose. The purpose of this study was to investigate the capacity for high fat diet (HFD)-induced obesity to alter adipose-derived stromal cell (ADSC) relative quantity and ECM gene expression, and determine the extent to which e...

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

    OpenAIRE

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

    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 ...

  16. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    OpenAIRE

    Eduardo R. Ropelle; Pauli, Jose R.; Prada, Patricia; Cintra, Dennys E.; Rocha, Guilherme Z; Juliana C Moraes; Frederico, Marisa J.S.; Luz,Gabrielle da; Pinho, Ricardo A.; Carvalheira, Jose B. C.; Velloso, Licio A.; Saad, Mario A.; Souza, Claudio T. de

    2009-01-01

    Insulin signalling in the hypothalamus plays a role in maintaining body weight. the forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induce...

  17. Weight loss enhances hepatic antioxidant status in a NAFLD model induced by high-fat diet.

    Science.gov (United States)

    Mendes, Iara Karise Santos; Matsuura, Cristiane; Aguila, Marcia Barbosa; Daleprane, Julio Beltrame; Martins, Marcela Anjos; Mury, Wanda Vianna; Brunini, Tatiana Marlowe Cunha

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a benign condition that can progress to more severe liver damage in a process mediated, in part, by disturbances in redox balance. Additionally, some argue that it is set to become the main cause of end-stage liver disease in the near future. Here, we investigated whether diet-induced weight loss is able to reverse hepatic lipid accumulation and reduce oxidative stress in liver from C57BL/6 mice fed a high-fat (HF) diet. Male C57BL/6 mice were divided into 4 groups: standard chow (SC; 10% energy from fat, 16 weeks); HF (50% energy from fat, 16 weeks); SC-HF (SC for 8 weeks followed by HF for 8 weeks); and HF-SC (HF for 8 weeks followed by SC for 8 weeks). The HF diet during 8 (SC-HF) and 16 weeks (HF) downregulated messenger RNA levels and protein expression of Nrf2 and endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) in the liver; caused liver steatosis; affected liver function markers; increased intra-abdominal and subcutaneous adipose tissue; and induced glucose intolerance and hypercholesterolemia compared with controls (SC). Diet-induced weight loss significantly reduced the intrahepatic lipid accumulation, improved glucose tolerance, and restored both gene and protein expression of the antioxidant enzymes. Our findings suggest that a dietary intervention aimed to induce weight loss may exert protective effects in NAFLD as it can reduce hepatic oxidative stress and intrahepatic lipid accumulation, which can hinder the progression of this condition to more severe states.

  18. Fish oil rich diet in comparison to saturated fat rich diet offered protection against lipopolysaccharide-induced inflammation and insulin resistance in mice

    Directory of Open Access Journals (Sweden)

    Ziegler Thomas R

    2011-03-01

    Full Text Available Abstract Background and Objective Systemic chronic inflammation is linked to metabolic syndrome, type-2 diabetes, and heart disease. Lipopolysaccharide (LPS, a Gram negative microbial product, triggers inflammation through toll-like-receptor-4 (TLR-4 signaling. It has been reported that dietary fatty acids also modulate inflammation through TLR-4. We investigated whether fish oil (FO rich diet in comparison to saturated fat (SF rich diet would confer protection from pathologies induced by LPS. Methods Twenty C57BL/6 mice were divided into two groups. One group received FO-diet and other received SF-diet ad libitum for 60 days. Diets were isocaloric containing 45% energy from fat. After 60-days of feeding, blood was collected after overnight fast. Mice were allowed to recover for 4-days, fasted for 5-hours, challenged with 100 ng/mL of LPS intraperitonially, and bled after 2-hours. After 7-days of recuperation, mice were challenged with 500 ng/mL of LPS intraperitonially and observed for physical health. Results Food intake was similar in FO- and SF-fed mice. FO-fed mice compared to SF-fed mice had significantly less body weight gain (P = 0.005, epididymal fat weight (P = 0.005, fasting blood glucose (70.8 vs 83.3 ng/dL; P Conclusion Overall, FO-diet compared to SF-diet offered protection against deleterious effects of LPS in mice.

  19. FcRγ-chain deficiency reduces the development of diet-induced obesity.

    Science.gov (United States)

    van Beek, Lianne; Vroegrijk, Irene O C M; Katiraei, Saeed; Heemskerk, Mattijs M; van Dam, Andrea D; Kooijman, Sander; Rensen, Patrick C N; Koning, Frits; Verbeek, J Sjef; Willems van Dijk, Ko; van Harmelen, Vanessa

    2015-12-01

    Pathogenic immunoglobulins are produced during the development of obesity and contribute to the development of insulin resistance (IR). However, the mechanisms by which these antibodies affect IR are largely unknown. This study investigated whether Fc-receptors contribute to the development of diet-induced obesity and IR by studying FcRγ(-/-) mice that lack the γ-subunit necessary for signaling and cell surface expression of FcγR and FcεRI. FcRγ(-/-) and wild-type (WT) mice were fed a high-fat diet (HFD) to induce obesity. At 4 and 11 weeks, body weight and insulin sensitivity were measured, and adipose tissue (AT) inflammation was determined. Furthermore, intestinal triglyceride (TG) uptake and plasma TG clearance were determined, and gut microbiota composition was analyzed. FcRγ(-/-) mice gained less weight after 11 weeks of HFD. They had reduced adiposity, adipose tissue inflammation, and IR. Interestingly, FcRγ(-/-) mice had higher lean mass compared to WT mice, which was associated with increased energy expenditure. Intestinal TG absorption was increased whereas plasma TG clearance was not affected in FcRγ(-/-) mice. Gut microbial composition differed significantly and might therefore have added to the observed phenotype. FcRγ-chain deficiency reduces the development of diet-induced obesity, as well as associated AT inflammation and IR at 11 weeks of HFD. © 2015 The Obesity Society.

  20. Dietary supplementation with a specific melon concentrate reverses vascular dysfunction induced by cafeteria diet

    Directory of Open Access Journals (Sweden)

    Julie Carillon

    2016-11-01

    Full Text Available Background: Obesity-related metabolic syndrome is associated with high incidence of cardiovascular diseases partially consecutive to vascular dysfunction. Therapeutic strategies consisting of multidisciplinary interventions include nutritional approaches. Benefits of supplementation with a specific melon concentrate, enriched in superoxide dismutase (SOD, have previously been shown on the development of insulin resistance and inflammation in a nutritional hamster model of obesity. Objective: We further investigated arterial function in this animal model of metabolic syndrome and studied the effect of melon concentrate supplementation on arterial contractile activity. Design and results: The study was performed on a hamster model of diet-induced obesity. After a 15-week period of cafeteria diet, animals were supplemented during 4 weeks with a specific melon concentrate (Cucumis melo L. Contractile responses of isolated aorta to various agonists and antagonists were studied ex vivo. Cafeteria diet induced vascular contractile dysfunction associated with morphological remodeling. Melon concentrate supplementation partially corrected these dysfunctions; reduced morphological alterations; and improved contractile function, especially by increasing nitric oxide bioavailability and expression of endogenous SOD. Conclusions: Supplementation with the specific melon concentrate improves vascular dysfunction associated with obesity. This beneficial effect may be accounted for by induction of endogenous antioxidant defense. Such an approach in line with nutritional interventions could be a useful strategy to manage metabolic syndrome–induced cardiovascular trouble.

  1. Effects of voluntary running and soy supplementation on diet-induced metabolic disturbances and inflammation in mice

    Science.gov (United States)

    The present study investigated the effects of voluntary running and soy supplementation on diet-induced metabolic disturbance and inflammation in male C57BL/6 mice using a 2x2x2 design in which the effects of diet (AIN93G or its modification with 45% calories from fat), activity level (sedentary or ...

  2. Qualitative and quantitative detection of honey adulterated with high-fructose corn syrup and maltose syrup by using near-infrared spectroscopy.

    Science.gov (United States)

    Li, Shuifang; Zhang, Xin; Shan, Yang; Su, Donglin; Ma, Qiang; Wen, Ruizhi; Li, Jiaojuan

    2017-03-01

    Near-infrared spectroscopy (NIR) was used for qualitative and quantitative detection of honey adulterated with high-fructose corn syrup (HFCS) or maltose syrup (MS). Competitive adaptive reweighted sampling (CARS) was employed to select key variables. Partial least squares linear discriminant analysis (PLS-LDA) was adopted to classify the adulterated honey samples. The CARS-PLS-LDA models showed an accuracy of 86.3% (honey vs. adulterated honey with HFCS) and 96.1% (honey vs. adulterated honey with MS), respectively. PLS regression (PLSR) was used to predict the extent of adulteration in the honeys. The results showed that NIR combined with PLSR could not be used to quantify adulteration with HFCS, but could be used to quantify adulteration with MS: coefficient (R p 2 ) and root mean square of prediction (RMSEP) were 0.901 and 4.041 for MS-adulterated samples from different floral origins, and 0.981 and 1.786 for MS-adulterated samples from the same floral origin (Brassica spp.), respectively. Copyright © 2016. Published by Elsevier Ltd.

  3. Properties of a novel thermostable glucose isomerase mined from Thermus oshimai and its application to preparation of high fructose corn syrup.

    Science.gov (United States)

    Jia, Dong-Xu; Zhou, Lin; Zheng, Yu-Guo

    2017-04-01

    Glucose isomerase (GI) is used in vitro to convert d-glucose to d-fructose, which is capable of commercial producing high fructose corn syrup (HFCS). To manufacture HFCS at elevated temperature and reduce the cost of enriching syrups, novel refractory GIs from Thermoanaerobacterium xylanolyticum (TxGI), Thermus oshimai (ToGI), Geobacillus thermocatenulatus (GtGI) and Thermoanaerobacter siderophilus (TsGI) were screened via genome mining approach. The enzymatic characteristics research showed that ToGI had higher catalytic efficiency and superior thermostability toward d-glucose among the screened GIs. Its optimum temperature reached 95°C and could retain more than 80% of initial activity in the presence of 20mM Mn(2+) at 85°C for 48h. The Km and kcat/Km values for ToGI were 81.46mM and 21.77min(-1)mM(-1), respectively. Furthermore, the maximum conversion yield of 400g/L d-glucose to d-fructose at 85°C was 52.16%. Considering its excellent high thermostability and ameliorable application performance, ToGI might be promising for realization of future industrial production of HFCS at elevated temperature. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Impact of the North American Free Trade Agreement on high-fructose corn syrup supply in Canada: a natural experiment using synthetic control methods.

    Science.gov (United States)

    Barlow, Pepita; McKee, Martin; Basu, Sanjay; Stuckler, David

    2017-07-04

    Critics of free trade agreements have argued that they threaten public health, as they eliminate barriers to trade in potentially harmful products, such as sugar. Here we analyze the North American Free Trade Agreement (NAFTA), testing the hypothesis that lowering tariffs on food and beverage syrups that contain high-fructose corn syrup (HFCS) increased its use in foods consumed in Canada. We used supply data from the Food and Agriculture Organization of the United Nations to assess changes in supply of caloric sweeteners including HFCS after NAFTA. We estimate the impact of NAFTA on supply of HFCS in Canada using an innovative, quasi-experimental methodology - synthetic control methods - that creates a control group with which to compare Canada's outcomes. Additional robustness tests were performed for sample, control groups and model specification. Tariff reductions in NAFTA coincided with a 41.6 (95% confidence interval 25.1 to 58.2) kilocalorie per capita daily increase in the supply of caloric sweeteners including HFCS. This change was not observed in the control groups, including Australia and the United Kingdom, as well as a composite control of 16 countries. Results were robust to placebo tests and additional sensitivity analyses. NAFTA was strongly associated with a marked rise in HFCS supply and likely consumption in Canada. Our study provides evidence that even a seemingly modest change to product tariffs in free trade agreements can substantially alter population-wide dietary behaviour and exposure to risk factors. © 2017 Canadian Medical Association or its licensors.

  5. Rare Sugar Syrup Containing d-Allulose but Not High-Fructose Corn Syrup Maintains Glucose Tolerance and Insulin Sensitivity Partly via Hepatic Glucokinase Translocation in Wistar Rats.

    Science.gov (United States)

    Shintani, Tomoya; Yamada, Takako; Hayashi, Noriko; Iida, Tetsuo; Nagata, Yasuo; Ozaki, Nobuaki; Toyoda, Yukiyasu

    2017-04-05

    Ingestion of high-fructose corn syrup (HFCS) is associated with the risk of both diabetes and obesity. Rare sugar syrup (RSS) has been developed by alkaline isomerization of HFCS and has anti-obesity and anti-diabetic effects. However, the influence of RSS on glucose metabolism has not been explored. We investigated whether long-term administration of RSS maintains glucose tolerance and whether the underlying mechanism involves hepatic glucokinase translocation. Wistar rats were administered water, RSS, or HFCS in drinking water for 10 weeks and then evaluated for glucose tolerance, insulin tolerance, liver glycogen content, and subcellular distribution of liver glucokinase. RSS significantly suppressed body weight gain and abdominal fat mass (p RSS group had significantly lower blood glucose levels from 90 to 180 min (p RSS group were significantly lower than those in the water group (p RSS group than that in the other groups. After glucose loading, the nuclear export of glucokinase was significantly increased in the RSS group compared to the water group. These results imply that RSS maintains glucose tolerance and insulin sensitivity, at least partly, by enhancing nuclear export of hepatic glucokinase.

  6. Impact of the North American Free Trade Agreement on high-fructose corn syrup supply in Canada: a natural experiment using synthetic control methods

    Science.gov (United States)

    Barlow, Pepita; McKee, Martin; Basu, Sanjay; Stuckler, David

    2017-01-01

    BACKGROUND: Critics of free trade agreements have argued that they threaten public health, as they eliminate barriers to trade in potentially harmful products, such as sugar. Here we analyze the North American Free Trade Agreement (NAFTA), testing the hypothesis that lowering tariffs on food and beverage syrups that contain high-fructose corn syrup (HFCS) increased its use in foods consumed in Canada. METHODS: We used supply data from the Food and Agriculture Organization of the United Nations to assess changes in supply of caloric sweeteners including HFCS after NAFTA. We estimate the impact of NAFTA on supply of HFCS in Canada using an innovative, quasi-experimental methodology — synthetic control methods — that creates a control group with which to compare Canada’s outcomes. Additional robustness tests were performed for sample, control groups and model specification. RESULTS: Tariff reductions in NAFTA coincided with a 41.6 (95% confidence interval 25.1 to 58.2) kilocalorie per capita daily increase in the supply of caloric sweeteners including HFCS. This change was not observed in the control groups, including Australia and the United Kingdom, as well as a composite control of 16 countries. Results were robust to placebo tests and additional sensitivity analyses. INTERPRETATION: NAFTA was strongly associated with a marked rise in HFCS supply and likely consumption in Canada. Our study provides evidence that even a seemingly modest change to product tariffs in free trade agreements can substantially alter population-wide dietary behaviour and exposure to risk factors. PMID:28676578

  7. Diets rich in saturated and polyunsaturated fatty acids induce morphological alterations in the rat ventral prostate.

    Directory of Open Access Journals (Sweden)

    Angélica Furriel

    Full Text Available To evaluate the influence of dietary lipid quality on the body mass, carbohydrate metabolism and morphology of the rat ventral prostate.Wistar rats were divided into four groups: SC (standard chow, HF-S (high-fat diet rich in saturated fatty acids, HF-P (high-fat diet rich in polyunsaturated fatty acids and HF-SP (high-fat diet rich in saturated and polyunsaturated fatty acids. We analyzed body mass, fat mass deposits, plasma blood, insulin resistance and the ventral prostate structure.Groups that received high-fat diets were heavier and presented larger fat deposits than SC group. The HF-S and HF-SP groups had higher glucose, insulin and total cholesterol serum levels and insulin resistance compared with the SC. The acinar area, epithelium height and area density of the lumen were higher in the HF-SP than in the other groups. The epithelium area density and epithelial cell proliferation were greater in the HF-P and HF-SP than in the SC group. All of the groups that received high-fat diets had greater area density of the stroma, area density of smooth muscle cells and stromal cell proliferation compared with the SC group.Diets rich in saturated and/or polyunsaturated fatty acids induced overweight. Independently of insulin resistance, polyunsaturated fatty acids increased prostate stromal and epithelial cell proliferation. Saturated fatty acids influenced only stromal cellular proliferation. These structural and morphometric alterations may be considered risk factors for the development of adverse remodeling process in the rat ventral prostate.

  8. Myocardial Structural and Biological Anomalies Induced by High Fat Diet in Psammomys obesus Gerbils.

    Directory of Open Access Journals (Sweden)

    Abdelhamid Sahraoui

    Full Text Available Psammomys obesus gerbils are particularly prone to develop diabetes and obesity after brief period of abundant food intake. A hypercaloric high fat diet has been shown to affect cardiac function. Here, we sought to determine whether a short period of high fat feeding might alter myocardial structure and expression of calcium handling proteins in this particular strain of gerbils.Twenty Psammomys obesus gerbils were randomly assigned to receive a normal plant diet (controls or a high fat diet. At baseline and 16-week later, body weight, plasma biochemical parameters (including lipid and carbohydrate levels were evaluated. Myocardial samples were collected for pathobiological evaluation.Sixteen-week high fat dieting resulted in body weight gain and hyperlipidemia, while levels of carbohydrates remained unchanged. At myocardial level, high fat diet induced structural disorganization, including cardiomyocyte hypertrophy, lipid accumulation, interstitial and perivascular fibrosis and increased number of infiltrating neutrophils. Myocardial expressions of pro-apoptotic Bax-to-Bcl-2 ratio, pro-inflammatory cytokines [interleukin (IL-1β and tumor necrosis factor (TNF-α], intercellular (ICAM1 and vascular adhesion molecules (VCAM1 increased, while gene encoding cardiac muscle protein, the alpha myosin heavy polypeptide (MYH6, was downregulated. Myocardial expressions of sarco(endoplasmic calcium-ATPase (SERCA2 and voltage-dependent calcium channel (Cacna1c decreased, while protein kinase A (PKA and calcium-calmodulin-dependent protein kinase (CaMK2D expressions increased. Myocardial expressions of ryanodine receptor, phospholamban and sodium/calcium exchanger (Slc8a1 did not change.We conclude that a relative short period of high fat diet in Psammomys obesus results in severe alterations of cardiac structure, activation of inflammatory and apoptotic processes, and altered expression of calcium-cycling determinants.

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

    Science.gov (United States)

    Trinko, Joseph R; Land, Benjamin B; Solecki, Wojciech B; Wickham, Robert J; Tellez, Luis A; Maldonado-Aviles, Jaime; de Araujo, Ivan E; Addy, Nii A; DiLeone, Ralph J

    2016-01-01

    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.

  10. Long term highly saturated fat diet does not induce NASH in Wistar rats

    Directory of Open Access Journals (Sweden)

    Filippi Céline

    2007-02-01

    Full Text Available Abstract Background Understanding of nonalcoholic steatohepatitis (NASH is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid or butter (51% of saturated fatty acid had an increased caloric intake (+143% and +30%. At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45% and butter (42% groups than in the standard (7% diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25–28% vs standard. Conclusion Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH.

  11. 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

    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...

  12. Adaptive facultative diet-induced thermogenesis in wild-type but not in UCP1-ablated mice.

    Science.gov (United States)

    von Essen, Gabriella; Lindsund, Erik; Cannon, Barbara; Nedergaard, Jan

    2017-11-01

    The significance of diet-induced thermogenesis (DIT) for metabolic control is still debated. Although obesogenic diets recruit UCP1 and adrenergically inducible thermogenesis, and although the absence of UCP1 may promote the development of obesity, no actual UCP1-related thermogenesis identifiable as diet-induced thermogenesis has to date been unambiguously demonstrated. Examining mice living at thermoneutrality, we have identified a process of facultative (directly elicited by acute eating), adaptive (magnitude develops over weeks on an obesogenic diet), and fully UCP1-dependent thermogenesis. We found no evidence for UCP1-independent diet-induced thermogenesis. The thermogenesis was proportional to the total amount of UCP1 protein in brown adipose tissue and was not dependent on any contribution of UCP1 in brite/beige adipose tissue, since no UCP1 protein was found there under these conditions. Total UCP1 protein amount developed proportionally to total body fat content. The physiological messenger linking obesity level and acute eating to increased thermogenesis is not known. Thus UCP1-dependent diet-induced thermogenesis limits obesity development during exposure to obesogenic diets but does not prevent obesity as such. Copyright © 2017 the American Physiological Society.

  13. The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases.

    Science.gov (United States)

    Williams, Lynda M; Campbell, Fiona M; Drew, Janice E; Koch, Christiane; Hoggard, Nigel; Rees, William D; Kamolrat, Torkamol; Thi Ngo, Ha; Steffensen, Inger-Lise; Gray, Stuart R; Tups, Alexander

    2014-01-01

    High-fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12-16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.

  14. The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases.

    Directory of Open Access Journals (Sweden)

    Lynda M Williams

    Full Text Available High-fat (HF diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT. However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT, in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12-16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.

  15. Experimental liver fibrosis induced in rats receiving high doses of alcohol and alternating between regular and vitamin-depleted diets.

    Science.gov (United States)

    Hirano, H; Hirano, T; Hirata, K; Tamura, M; Yamaura, T; Hamada, T

    1996-07-15

    Liver fibrosis was induced in rats by simulating human alcoholic eating and drinking patterns. Alcohol addiction was established by gradually increasing the ethanol concentration in the drinking water; salts were added at the terminal stage. The hepatocytes of rats receiving alcohol concentrations exceeding 50% (v/v) (similar to vodka) exhibited alcoholic hyaline (Mallory bodies). Alcoholic liver fibrosis was induced by alternating between regular and autoclaved (vitamin-depleted) diets, simulating the irregular eating habits of human alcoholics. In the livers of rats receiving 70% (v/v) ethanol (comparable to absinthe) with 25% saline and fed the alternating diets, pericellular fibrosis was induced. No significant difference in calorie intake between control and alcohol rats was detected except when rats underwent drinking bouts (heavy drinking phase). This indicates that neither a high-fat diet nor a choline-depleted diet is necessary to induce the alcoholic fibrosis seen in human alcoholics.

  16. Administration of Lactobacillus gasseri SBT2055 suppresses macrophage infiltration into adipose tissue in diet-induced obese mice

    National Research Council Canada - National Science Library

    Ukibe, Ken; Miyoshi, Masaya; Kadooka, Yukio

    2015-01-01

    Administration of Lactobacillus gasseri SBT2055 (LG2055) has been shown to prevent body weight gain and it also down-regulates the expression of the Ccl2 gene in adipose tissue in diet-induced obese mice...

  17. Aged garlic extract enhances exercise-mediated improvement of metabolic parameters in high fat diet-induced obese rats

    National Research Council Canada - National Science Library

    Dae Yun Seo; SungRyul Lee; Arturo Figueroa; Yi Sub Kwak; Nari Kim; Byoung Doo Rhee; Kyung Soo Ko; Hyun Seok Bang; Yeong Ho Baek; Jin Han

    2012-01-01

    .... We examined the effects of exercise with and without aged garlic extract administration on body weight, lipid profiles, inflammatory cytokines, and oxidative stress marker in high-fat diet (HFD)-induced obese rats...

  18. Diets higher in dairy foods and dietary protein support bone health during diet- and exercise-induced weight loss in overweight and obese premenopausal women.

    Science.gov (United States)

    Josse, Andrea R; Atkinson, Stephanie A; Tarnopolsky, Mark A; Phillips, Stuart M

    2012-01-01

    Consolidation and maintenance of peak bone mass in young adulthood may be compromised by inactivity, low dietary calcium, and diet-induced weight loss. We aimed to determine whether higher intakes of dairy foods, dietary calcium, and protein during diet- and exercise-induced weight loss affected markers of bone health. Participants included premenopausal overweight and obese women. Ninety participants were randomized into three groups (n = 30 per group): high protein and high dairy (HPHD), adequate protein and medium dairy (APMD), and adequate protein and low dairy (APLD), differing in dietary protein (30, 15, or 15% of energy, respectively), dairy foods (15, 7.5, or protein, respectively), and dietary calcium (∼1600, ∼1000, or dietary calcium, and protein with daily exercise, favorably affected important bone health biomarkers vs. diets with less of these bone-supporting nutrients.

  19. MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.

    Science.gov (United States)

    Di Pasqua, Laura G; Berardo, Clarissa; Rizzo, Vittoria; Richelmi, Plinio; Croce, Anna Cleta; Vairetti, Mariapia; Ferrigno, Andrea

    2016-08-01

    Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8-week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8 weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8 weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH.

  20. Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats.

    Science.gov (United States)

    Sharma, Bhavna; Salunke, Rajani; Srivastava, Swati; Majumder, Chandrajeetbalo; Roy, Partha

    2009-10-01

    Sedentary lifestyle, consumption of energy-rich diet, obesity and longer lifespan are some of the major reasons for the rise of metabolic disorders like type II diabetes, obesity, hypertension and dyslipidemia among people of various age groups. High fat diet induced diabetic rodent models resembling type II diabetic condition in human population were used to assess the anti-diabetic and hypolipidemic activity of guggulsterone (isolated from Commiphora mukul resin). Four groups of rats were fed high fat diet, for 16 weeks. On feeding the normal rats with fat rich diet they showed increased serum glucose, cholesterol and triglyceride levels along with increase in insulin resistance significantly (p<0.05) in comparison to control animals. Different biochemical parameters like GTT, glycogen content, glucose homeostatic enzymes (like glucose-6-phosphatase, hexokinase), insulin release in vivo and expression profiles of various genes involved in carbohydrate and lipid metabolism clearly demonstrated the hypoglycemic effect of this extract. Guggulsterone demonstrated a differential effect with a significantly improved PPARgamma expression and activity in in vivo and in vitro conditions, respectively. However, it inhibited 3T3-L1 preadipocytes differentiation in vitro. The results presented here suggest that the guggulsterone has both hypoglycemic and hypolipidemic effect which can help to cure type II diabetes.

  1. Salicornia herbacea prevents high fat diet-induced hyperglycemia and hyperlipidemia in ICR mice.

    Science.gov (United States)

    Park, Sang Hyun; Ko, Sung Kwon; Choi, Jin Gyu; Chung, Sung Hyun

    2006-03-01

    Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.

  2. A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.

    Science.gov (United States)

    Li, Ling; Zhang, Guo-Fang; Lee, Kwangwon; Lopez, Rocio; Previs, Stephen F; Willard, Belinda; McCullough, Arthur; Kasumov, Takhar

    2016-07-01

    Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepatic glutathione metabolism in patients with NAFLD. As a primary source of plasma glutathione, liver plays an important role in interorgan glutathione homeostasis. In this study, we have tested the hypothesis that measurements of plasma glutathione turnover could be used to assess the hepatic glutathione metabolism in LDLR(-/)(-) mice, a mouse model of diet-induced NAFLD. Mice were fed a standard low fat diet (LFD) or a high fat diet containing cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma glutathione were quantified using the (2)H2O metabolic labeling approach. Our results show that a WD leads to reduced fractional synthesis rates (FSR) of hepatic (25%/h in LFD vs. 18%/h in WD, Pplasma glutathione (43%/h in LFD vs. 21%/h in WD, Pinduced concordant changes in both hepatic and plasma glutathione turnover suggest that the plasma glutathione turnover measurements could be used to assess hepatic glutathione metabolism. The safety, simplicity, and low cost of the (2)H2O-based glutathione turnover approach suggest that this method has the potential for non-invasive probing of hepatic glutathione metabolism in patients with NAFLD and other diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Protective effect of lycopene on high-fat diet-induced cognitive impairment in rats.

    Science.gov (United States)

    Wang, Zhiqiang; Fan, Jin; Wang, Jian; Li, Yuxia; Xiao, Li; Duan, Dan; Wang, Qingsong

    2016-08-03

    A Western diet, high in saturated fats, has been linked to the development of cognitive impairment. Lycopene has recently received considerable attention for its potent protective properties demonstrated in several models of nervous system dysfunction. However, it remains unclear whether lycopene exerts protective effects on cognition. The present study aimed to investigate the protective effects of lycopene on learning and memory impairment and the potential underlying mechanism in rats fed a high-fat diet (HFD). One-month-old male rats were fed different diets for 16 weeks (n=12 per group), including a standard chow diet (CD), a HFD, or a HFD plus lycopene (4mg/kg, oral gavage in the last three weeks). Behavioral testing, including the Morris water maze (MWM), object recognition task (ORT), and anxiety-like behavior in an open field (OF), were assessed at week 16. The dendritic spine density and neuronal density in the hippocampal CA1 subfield were subsequently measured. The results indicate that HFD consumption for 16 weeks significantly impaired spatial memory (Plycopene significantly attenuated learning and memory impairments and prevented the reduction in dendritic spine density (Plycopene helps to protect HFD induced cognitive dysfunction. Copyright © 2016. Published by Elsevier Ireland Ltd.

  4. Epigenetic dysregulation of the dopamine system in diet-induced obesity.

    Science.gov (United States)

    Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

    2012-03-01

    Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  5. Metformin Affects Cortical Bone Mass and Marrow Adiposity in Diet-Induced Obesity in Male Mice.

    Science.gov (United States)

    Bornstein, Sheila; Moschetta, Michele; Kawano, Yawara; Sacco, Antonio; Huynh, Daisy; Brooks, Daniel; Manier, Salomon; Fairfield, Heather; Falank, Carolyne; Roccaro, Aldo M; Nagano, Kenichi; Baron, Roland; Bouxein, Mary; Vary, Calvin; Ghobrial, Irene M; Rosen, Clifford J; Reagan, Michaela R

    2017-10-01

    Obesity during maturation can affect the growing skeleton directly and indirectly, although these effects and the mechanisms behind them are not fully understood. Our objective was to determine how a high-fat diet with or without metformin treatment affects skeletal development. We also sought to characterize changes that occur in white adipose tissue, circulating metabolites, lipids, and gut microbiota. A diet-induced obesity C57BL/6J mouse model was used to test the effects of obesity and metformin on bone using bone histomorphometry and microcomputed tomography. Bone marrow adipose tissue was quantified with osmium tetroxide microcomputed tomography and histology. Dual-energy x-ray absorptiometry was used to analyze body composition. Hematoxylin and eosin staining was used to assess changes in white adipose depots, mass spectrometry was used for circulating lipids and protein metabolite analysis, and ribosomal RNA sequencing was used for gut microbiome analysis. Mice fed a high fat-diet since wean displayed increased medullary areas and decreased osteoblast numbers in the long bones; this phenotype was partially normalized by metformin. Marrow and inguinal adipose expansion was also noted in obese mice, and this was partially normalized by metformin. A drug-by-diet interaction was noted for circulating lipid molecules, protein metabolites, and gut microbiome taxonomical units. Obesity was not detrimental to trabecular bone in growing mice, but bone marrow medullary expansion was observed, likely resulting from inhibition of osteoblastogenesis, and this was partially reversed by metformin treatment. Copyright © 2017 Endocrine Society.

  6. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

    Science.gov (United States)

    Lauritzen, Knut H; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Scheibye-Knudsen, Morten; Gjedde, Albert; Klungland, Arne; Bohr, Vilhelm A; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-12-01

    Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABA A ) receptor subunits α 1 . However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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.

  9. Molecular fingerprint of high fat diet induced urinary bladder metabolic dysfunction in a rat model.

    Directory of Open Access Journals (Sweden)

    Andreas Oberbach

    Full Text Available AIMS/HYPOTHESIS: Diabetic voiding dysfunction has been reported in epidemiological dimension of individuals with diabetes mellitus. Animal models might provide new insights into the molecular mechanisms of this dysfunction to facilitate early diagnosis and to identify new drug targets for therapeutic interventions. METHODS: Thirty male Sprague-Dawley rats received either chow or high-fat diet for eleven weeks. Proteomic alterations were comparatively monitored in both groups to discover a molecular fingerprinting of the urinary bladder remodelling/dysfunction. Results were validated by ELISA, Western blotting and immunohistology. RESULTS: In the proteome analysis 383 proteins were identified and canonical pathway analysis revealed a significant up-regulation of acute phase reaction, hypoxia, glycolysis, β-oxidation, and proteins related to mitochondrial dysfunction in high-fat diet rats. In contrast, calcium signalling, cytoskeletal proteins, calpain, 14-3-3η and eNOS signalling were down-regulated in this group. Interestingly, we found increased ubiquitin proteasome activity in the high-fat diet group that might explain the significant down-regulation of eNOS, 14-3-3η and calpain. CONCLUSIONS/INTERPRETATION: Thus, high-fat diet is sufficient to induce significant remodelling of the urinary bladder and alterations of the molecular fingerprint. Our findings give new insights into obesity related bladder dysfunction and identified proteins that may indicate novel pathophysiological mechanisms and therefore constitute new drug targets.

  10. Molecular fingerprint of high fat diet induced urinary bladder metabolic dysfunction in a rat model.

    Science.gov (United States)

    Oberbach, Andreas; Jehmlich, Nico; Schlichting, Nadine; Heinrich, Marco; Lehmann, Stefanie; Wirth, Henry; Till, Holger; Stolzenburg, Jens-Uwe; Völker, Uwe; Adams, Volker; Neuhaus, Jochen

    2013-01-01

    Diabetic voiding dysfunction has been reported in epidemiological dimension of individuals with diabetes mellitus. Animal models might provide new insights into the molecular mechanisms of this dysfunction to facilitate early diagnosis and to identify new drug targets for therapeutic interventions. Thirty male Sprague-Dawley rats received either chow or high-fat diet for eleven weeks. Proteomic alterations were comparatively monitored in both groups to discover a molecular fingerprinting of the urinary bladder remodelling/dysfunction. Results were validated by ELISA, Western blotting and immunohistology. In the proteome analysis 383 proteins were identified and canonical pathway analysis revealed a significant up-regulation of acute phase reaction, hypoxia, glycolysis, β-oxidation, and proteins related to mitochondrial dysfunction in high-fat diet rats. In contrast, calcium signalling, cytoskeletal proteins, calpain, 14-3-3η and eNOS signalling were down-regulated in this group. Interestingly, we found increased ubiquitin proteasome activity in the high-fat diet group that might explain the significant down-regulation of eNOS, 14-3-3η and calpain. Thus, high-fat diet is sufficient to induce significant remodelling of the urinary bladder and alterations of the molecular fingerprint. Our findings give new insights into obesity related bladder dysfunction and identified proteins that may indicate novel pathophysiological mechanisms and therefore constitute new drug targets.

  11. Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice

    Science.gov (United States)

    2010-01-01

    Introduction Obesity is a major risk factor for the development of osteoarthritis in both weight-bearing and nonweight-bearing joints. The mechanisms by which obesity influences the structural or symptomatic features of osteoarthritis are not well understood, but may include systemic inflammation associated with increased adiposity. In this study, we examined biomechanical, neurobehavioral, inflammatory, and osteoarthritic changes in C57BL/6J mice fed a high-fat diet. Methods Female C57BL/6J mice were fed either a 10% kcal fat or a 45% kcal fat diet from 9 to 54 weeks of age. Longitudinal changes in musculoskeletal function and inflammation were compared with endpoint neurobehavioral and osteoarthritic disease states. Bivariate and multivariate analyses were conducted to determine independent associations with diet, percentage body fat, and knee osteoarthritis severity. We also examined healthy porcine cartilage explants treated with physiologic doses of leptin, alone or in combination with IL-1α and palmitic and oleic fatty acids, to determine the effects of leptin on cartilage extracellular matrix homeostasis. Results High susceptibility to dietary obesity was associated with increased osteoarthritic changes in the knee and impaired musculoskeletal force generation and motor function compared with controls. A high-fat diet also induced symptomatic characteristics of osteoarthritis, including hyperalgesia and anxiety-like behaviors. Controlling for the effects of diet and percentage body fat with a multivariate model revealed a significant association between knee osteoarthritis severity and serum levels of leptin, adiponectin, and IL-1α. Physiologic doses of leptin, in the presence or absence of IL-1α and fatty acids, did not substantially alter extracellular matrix homeostasis in healthy cartilage explants. Conclusions These results indicate that diet-induced obesity increases the risk of symptomatic features of osteoarthritis through changes in

  12. Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats.

    Science.gov (United States)

    Goularte, Jéferson F; Ferreira, Maria B C; Sanvitto, Gilberto L

    2012-10-28

    Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.

  13. Palmitate diet-induced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction.

    Directory of Open Access Journals (Sweden)

    Catherine J Knowles

    Full Text Available Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate, and MCT diet (21% medium-chain triglycerides, no palmitate. We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.

  14. Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

    Science.gov (United States)

    Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

    2016-07-01

    The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Diet-Induced Alterations in Gut Microflora Contribute to Lethal Pulmonary Damage in TLR2/TLR4-Deficient Mice

    Directory of Open Access Journals (Sweden)

    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.

  16. Sweet potato (Ipomoea batatas) attenuates diet-induced aortic stiffening independent of changes in body composition.

    Science.gov (United States)

    Garner, Tyler; Ouyang, An; Berrones, Adam J; Campbell, Marilyn S; Du, Bing; Fleenor, Bradley S

    2017-08-01

    We hypothesized a sweet potato intervention would prevent high-fat (HF) diet-induced aortic stiffness, which would be associated with decreased arterial oxidative stress and increased mitochondrial uncoupling. Young (8-week old) C57BL/6J mice were randomly divided into 4 groups: low fat (LF; 10% fat), HF (60% fat), low-fat sweet potato (LFSP; 10% fat containing 260.3 μg/kcal sweet potato), or high-fat sweet potato diet (HFSP; 60% fat containing 260.3 μg/kcal sweet potato) for 16 weeks. Compared with LF and LFSP, HF- and HFSP-fed mice had increased body mass and percent fat mass with lower percent lean mass (all, P Sweet potato intervention did not influence body composition (all, P > 0.05). Arterial stiffness, assessed by aortic pulse wave velocity and ex vivo mechanical testing of the elastin region elastic modulus (EEM) was greater in HF compared with LF and HFSP animals (all, P sweet potato attenuates diet-induced aortic stiffness independent of body mass and composition, which is associated with a normalization of arterial oxidative stress possibly due to mitochondrial uncoupling.

  17. Metabolic Effects of Sleeve Gastrectomy in a Female Rat Model of Diet-Induced Obesity

    Science.gov (United States)

    Brinckerhoff, Tatiana Z.; Bondada, Sandhya; Lewis, Catherine E.; French, Sam; DeUgarte, Daniel A.

    2011-01-01

    Background While females disproportionately undergo bariatric surgery, rodent models investigating mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients as it avoids the malabsorption associated with intestinal bypass. Objectives We sought to evaluate the impact of sleeve gastrectomy on young female rats with diet-induced obesity. Settings David Geffen School of Medicine at UCLA Methods Sprague Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, animals underwent either sleeve gastrectomy or sham surgery. Animals were sacrificed four weeks after surgery. A chemistry panel was performed, and serum adipokines and gut hormones were assayed. Homeostasis model assessment score (HOMA) was calculated. Liver histology was graded for steatosis. Two-sample t-test was used to compare groups. Results Sleeve gastrectomy was associated with significant weight loss (5±6% vs. −4±6%; pSleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin via mechanisms independent of ghrelin in a female model of diet-induced obesity. PMID:22093377

  18. 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 (Pobesity-related hypertension. © 2016 American Heart Association, Inc.

  19. Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver.

    Science.gov (United States)

    Davaatseren, Munkhtugs; Hur, Haeng Jeon; Yang, Hye Jeong; Hwang, Jin-Taek; Park, Jae Ho; Kim, Hyun-Jin; Kim, Min Jung; Kwon, Dae Young; Sung, Mi Jeong

    2013-08-01

    The purpose of this study is to determine the protective effect of Taraxacum official (dandelion) leaf extract (DLE) on high-fat-diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. To determine the hepatoprotective effect of DLE, we fed C57BL/6 mice with normal chow diet (NCD), high-fat diet (HFD), HFD supplemented with 2g/kg DLE DLE (DL), and HFD supplemented with 5 g/kg DLE (DH). We found that the HFD supplemented by DLE dramatically reduced hepatic lipid accumulation compared to HFD alone. Body and liver weights of the DL and DH groups were significantly lesser than those of the HFD group, and DLE supplementation dramatically suppressed triglyceride (TG), total cholesterol (TC), insulin, fasting glucose level in serum, and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) induced by HFD. In addition, DLE treatment significantly increased activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in liver and muscle protein. DLE significantly suppressed lipid accumulation in the liver, reduced insulin resistance, and lipid in HFD-fed C57BL/6 mice via the AMPK pathway. These results indicate that the DLE may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity.

    Science.gov (United States)

    Li, G; Liu, J-Y; Zhang, H-X; Li, Q; Zhang, S-W

    2015-01-01

    It is known that excessive sympathetic activity and oxidative stress are enhanced in obesity. This study aimed to clarify whether exercise training (ET) attenuates sympathetic activation and oxidative stress in obesity. The obesity was induced by high-fat diet (HFD) for 12 weeks. Male Sprague-Dawley rats were assigned to four groups: regular diet (RD) plus sedentary (RD-S), RD plus ET (RD-ET), HFD plus sedentary (HFD-S), and HFD plus ET (HFD-ET). The rats in RD-ET and HFD-ET groups were trained on a motorized treadmill for 60 min/day, five days/week for 8 weeks. The sympathetic activity was evaluated by the plasma norepinephrine (NE) level. The superoxide anion, malondialdehyde and F2-isoprostanes levels in serum and muscles were measured to evaluate oxidative stress. The ET prevented the increases in the body weight, arterial pressure and white adipose tissue mass in HFD rats. The NE level in plasma and oxidative stress related parameters got lower in HFD-ET group compared with HFD-S group. We have found decreased mRNA and protein levels of toll-like receptor (TLR)-2 and TLR-4 by ET in HFD rats. These findings suggest that ET may be effective for attenuating sympathetic activation and oxidative stress in diet-induced obesity.

  1. Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.

    Directory of Open Access Journals (Sweden)

    June-Chul Lee

    Full Text Available Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

  2. High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy.

    Science.gov (United States)

    Hsu, Hsiu-Ching; Chen, Ching-Yi; Lee, Bai-Chin; Chen, Ming-Fong

    2016-10-01

    Excessive fat intake induces obesity and causes cardiac injury. Intracellular degradation process involving destruction of long-lived proteins and organelles maintains homeostasis for cells under stress. The purpose of this study was to explore the relation of high-fat diet (HFD)-induced cardiac injury and intracellular degradation process with regard to autophagy and ER stress. HFD feeding for 24 weeks induced hyperglycemia, hyperlipidemia, and cardiac hypertrophy in adult male C57BL/6 mice. In the heart, PARP cleavage, an indicator of apoptosis, levels of LC3-II and p62, indicators of autophagy, and CHOP, indicator of ER stress, were increased. A palmitate-treated cardiomyoblast (H9C2) cell culture was examined to explore how HFD induced myocardial injury. Excessive palmitate (400 μM) treatment induced apoptosis and increased the number of autophagosomes and acid vacuoles of H9C2 cells. Besides, it elevated the expression of LC3-II, p62, and PARP cleavage. Induction of autophagy by rapamycin ameliorated palmitate-induced apoptosis, while inhibition of autophagy by 3-methyladenine or LC3 siRNA exacerbated palmitate-induced apoptosis. Palmitate treatment also induced CHOP expression which is associated with ER stress. HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition.

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

    OpenAIRE

    Jarinyaporn Naowaboot; Supaporn Wannasiri

    2016-01-01

    Objective: To examine the effect of Senna alata (S. alata) leaf extracts on the regulation of lipid metabolism in high-fat diet-induced obese mice. Methods: The obesity condition was induced in the male ICR mice by feeding them with high-fat diet (45 kcal% fat) for 12 weeks. At the 7th week of diet feeding, the obese mice were treated with the water extract of S. alata leaf at 250 and 500 mg/kg/day, respectively, that continued for six weeks. At the end of the treatment period, the biochem...

  4. The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity.

    Science.gov (United States)

    Rauckhorst, Adam J; Gray, Lawrence R; Sheldon, Ryan D; Fu, Xiaorong; Pewa, Alvin D; Feddersen, Charlotte R; Dupuy, Adam J; Gibson-Corley, Katherine N; Cox, James E; Burgess, Shawn C; Taylor, Eric B

    2017-11-01

    Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. The goal of this investigation was to test whether hepatocyte MPC disruption provides sustained protection from hyperglycemia during long-term HFD and the differential effects of hepatocyte MPC disruption on TCA cycle metabolism in NCD versus HFD conditions. We utilized long-term high fat feeding, serial measurements of postabsorptive blood glucose and metabolomic profiling and 13C-lactate/13C-pyruvate tracing to investigate the contribution of the MPC to hyperglycemia and altered hepatic TCA cycle metabolism during HFD-induced obesity. Hepatocyte MPC disruption resulted in long-term attenuation of hyperglycemia induced by HFD. HFD increased hepatic mitochondrial pyruvate utilization and TCA cycle capacity in an MPC-dependent manner. Furthermore, MPC disruption decreased progression of fibrosis and levels of transcript markers of inflammation. By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  5. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

    Science.gov (United States)

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

    2013-01-01

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P obesity. PMID:23883680

  6. Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures.

    Science.gov (United States)

    Holm, Jacob Bak; Rønnevik, Alexander; Tastesen, Hanne Sørup; Fjære, Even; Fauske, Kristin Røen; Liisberg, Ulrike; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

    2016-05-01

    High protein diets may protect against diet-induced obesity, but little is known regarding the effects of different protein sources consumed at standard levels. We investigated how a mixture of lean seafood or lean meat in a Western background diet modulated diet-induced obesity, energy metabolism and gut microbiota. Male C57BL/6J mice fed a Western diet (WD) containing a mixture of lean seafood (seafood WD) for 12weeks accumulated less fat mass than mice fed a WD containing a mixture of lean meat (meat WD). Meat WD-fed mice exhibited increased fasting blood glucose, impaired glucose clearance, elevated fasting plasma insulin and increased plasma and liver lipid levels. We observed no first choice preference for either of the WDs, but over time, mice fed the seafood WD consumed less energy than mice fed the meat WD. Mice fed the seafood WD exhibited higher spontaneous locomotor activity and a lower respiratory exchange ratio (RER) than mice fed the meat WD. Thus, higher activity together with the decreased energy intake contributed to the different phenotypes observed in mice fed the seafood WD compared to mice fed the meat WD. Comparison of the gut microbiomes of mice fed the two WDs revealed significant differences in the relative abundance of operational taxonomic units (OTUs) belonging to the orders Bacteroidales and Clostridiales, with genes involved in metabolism of aromatic amino acids exhibiting higher relative abundance in the microbiomes of mice fed the seafood WD. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Diet-induced obesity in ad libitum-fed mice: food texture overrides the effect of macronutrient composition.

    Science.gov (United States)

    Desmarchelier, Charles; Ludwig, Tobias; Scheundel, Ronny; Rink, Nadine; Bader, Bernhard L; Klingenspor, Martin; Daniel, Hannelore

    2013-04-28

    Diet-induced obesity in mice can be achieved through the use of diets with different macronutrient compositions and textures. We aimed at determining the contribution of macronutrient composition to obesity development and associated pathophysiological changes in mice. C57BL/6N mice were offered a control, a high-fat or a Western-style diet, either as pellet (H for hard) or with identical composition in powder form (S for soft), resulting in C-S, C-H, HF-H, HF-S, W-H and W-S groups, respectively. Body fat distribution, expression levels of selected target genes in adipose tissues, clinical chemistry and hormone concentration in the blood, as well as liver TAG content were measured. The most striking finding was that all mice fed the different powder diets developed obesity with similar weight gain, whereas among the mice fed the pellet diets, only those given the HF and W diets became obese. This allowed us to separate diet-specific effects from obesity-mediated effects. Irrespective of the food texture, the W diet induced a more severe hepatosteatosis and higher activities of serum transaminases compared with the two other diets. Adipose tissue gene expression analysis revealed that leptin and adiponectin levels were not affected by the dietary composition per se, whereas uncoupling protein 1 and 11β-hydroxysteroid dehydrogenase type 1 levels were decreased by both dietary composition and changes in body weight. In conclusion, diets differing in macronutrient composition elicit specific pathophysiological changes, independently of changes in body weight. A diet high in both fat and sugars seems to be more deleterious for the liver than a HF diet.

  8. Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

    Science.gov (United States)

    Thatcher, Brendan S.; Reidelberger, Roger D.; Ogimoto, Kayoko; Wolden-Hanson, Tami; Baskin, Denis G.; Schwartz, Michael W.; Blevins, James E.

    2012-01-01

    Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fak/fak) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs. PMID:22008455

  9. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.

    Science.gov (United States)

    Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

    2012-11-01

    We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥ 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.

  10. Dmbt1 does not affect a Western style diet-induced liver damage in mice

    DEFF Research Database (Denmark)

    Reichold, Astrid; Brenner, Sibylle A; Förster-Fromme, Karin

    2013-01-01

    Western style diet fed groups gained significant more weight than the controls and developed a mild non-alcoholic steatohepatitis. The presence/absence of functional Deleted in malignant brain tumors 1 had no effect on parameters like food intake, weight gain, fasting glucose, and liver damage....... These results suggest that Deleted in malignant brain tumors 1 plays a minor part on the development of a diet-induced liver damage in mice....... of non-alcoholic fatty liver disease. Concerning liver diseases, it is known that Deleted in malignant brain tumors 1 is amongst others related to liver injury and repair. In addition Deleted in malignant brain tumors 1 seems to play a role in regard to the maintenance of the intestinal homeostasis...

  11. High fat diet aggravates arsenic induced oxidative stress in rat heart and liver.

    Science.gov (United States)

    Dutta, Mousumi; Ghosh, Debosree; Ghosh, Arnab Kumar; Bose, Gargi; Chattopadhyay, Aindrila; Rudra, Smita; Dey, Monalisa; Bandyopadhyay, Arkita; Pattari, Sanjib K; Mallick, Sanjaya; Bandyopadhyay, Debasish

    2014-04-01

    Arsenic is a well known global groundwater contaminant. Exposure of human body to arsenic causes various hazardous effects via oxidative stress. Nutrition is an important susceptible factor which can affect arsenic toxicity by several plausible mechanisms. Development of modern civilization led to alteration in the lifestyle as well as food habits of the people both in urban and rural areas which led to increased use of junk food containing high level of fat. The present study was aimed at investigating the effect of high fat diet on heart and liver tissues of rats when they were co-treated with arsenic. This study was established by elucidating heart weight to body weight ratio as well as analysis of the various functional markers, oxidative stress biomarkers and also the activity of the antioxidant enzymes. Histological analysis confirmed the biochemical investigations. From this study it can be concluded that high fat diet increased arsenic induced oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. The histone acetyltransferase MOF activates hypothalamic polysialylation to prevent diet-induced obesity in mice

    Science.gov (United States)

    Brenachot, Xavier; Rigault, Caroline; Nédélec, Emmanuelle; Laderrière, Amélie; Khanam, Tasneem; Gouazé, Alexandra; Chaudy, Sylvie; Lemoine, Aleth; Datiche, Frédérique; Gascuel, Jean; Pénicaud, Luc; Benani, Alexandre

    2014-01-01

    Overfeeding causes rapid synaptic remodeling in hypothalamus feeding circuits. Polysialylation of cell surface molecules is a key step in this neuronal rewiring and allows normalization of food intake. Here we examined the role of hypothalamic polysialylation in the long-term maintenance of body weight, and deciphered the molecular sequence underlying its nutritional regulation. We found that upon high fat diet (HFD), reduced hypothalamic polysialylation exacerbated the diet-induced obese phenotype in mice. Upon HFD, the histone acetyltransferase MOF was rapidly recruited on the St8sia4 polysialyltransferase-encoding gene. Mof silencing in the mediobasal hypothalamus of adult mice prevented activation of the St8sia4 gene transcription, reduced polysialylation, altered the acute homeostatic feeding response to HFD and increased the body weight gain. These findings indicate that impaired hypothalamic polysialylation contribute to the development of obesity, and establish a role for MOF in the brain control of energy balance. PMID:25161885

  13. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin.

    Science.gov (United States)

    de Lartigue, Guillaume; de La Serre, Claire Barbier; Raybould, Helen E

    2011-11-30

    The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal afferent function is altered. This review will summarize recent findings on changes in vagal afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. 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

    complications is still elusive. In the present study, we investigated the impact of GPRC6A deficiency in a murine model of diet-induced obesity (DIO). Male Gprc6a knockout (KO) mice and WT littermates were subjected to a high-fat diet (HFD) for 25 weeks and exposed to comprehensive metabolic phenotyping...... in 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......The recently identified G protein-coupled receptor GPRC6A is activated by dietary amino acids and expressed in multiple tissues. Although the receptor is hypothesised to exert biological impact on metabolic and endocrine-related parameters, the role of the receptor in obesity and metabolic...

  15. Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice.

    Directory of Open Access Journals (Sweden)

    Sylvain Lengacher

    Full Text Available The monocarboxylate transporter 1 (MCT1 or SLC16A1 is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 (+/- mice developed normally. However, when fed high fat diet (HFD, MCT1 (+/- mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD, as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1 (+/+ mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1 (+/- mice was due to decreased fat accumulation (50.0% less after 9 months of HFD notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks and decreased intestinal energy absorption (9.6% higher stool energy content. Indirect calorimetry measurements showed ∼ 15% increase in O₂ consumption and CO₂ production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 (+/+ mice when fed HFD, were reduced in MCT1 (+/- mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 (+/+ mice under high fat diet was prevented in the liver of MCT1 (+/- mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet.

  16. Beneficial effects of Plantago albicans on high-fat diet-induced obesity in rats.

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    Samout, Noura; Ettaya, Amani; Bouzenna, Hafsia; Ncib, Sana; Elfeki, Abdelfattah; Hfaiedh, Najla

    2016-12-01

    Obesity is a one of the main global public health problems associated with chronic diseases such as coronary heart disease, diabetes and cancer. As a solution to obesity, we suggest Plantago albicans, which is a medicinal plant with several biological effects. This study assesses the possible anti-obesity protective properties of Plantago albicans in high fat diet-fed rats. 28 male Wistar rats were divided into 4 groups; a group which received normal diet (C), the second group was fed HDF diet (HDF), the third group was given normal diet supplemented with Plantago albicans (P.AL), and the fourth group received HDF supplemented with Plantago albicans (HDF+P.AL) (30mg/kg/day) for 7 weeks. Our results showed an increase in body weight of HDF rats by ∼16% as compared to the control group with an increase in the levels of total cholesterol (TC) as well as LDL-cholesterol, triglycerides (TG) in serum. Also, the concentration of TBARS increased in the liver and heart of HDF-fed rats as compared to the control group. The oral gavage of Plantago albicans extract to obese rats induced a reduction in their body weight, lipid accumulation in liver and heart tissue, compared to the high-fat diet control rats. The obtained results proved that the antioxidant potency of Plantago albicans extracts was correlated with their phenolic and flavonoid contents. The antioxidant capacity of the extract was evaluated by DPPH test (as EC50=250±2.12μg/mL) and FRAP tests (as EC50=27.77±0.14μg/mL). These results confirm the phytochemical and antioxidant impact of Plantago albicans extracts. Plantago albicans content was determined using validated HPLC methodology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Maternal diet during pregnancy induces gene expression and DNA methylation changes in fetal tissues in sheep

    Directory of Open Access Journals (Sweden)

    Xianyong eLan

    2013-04-01

    Full Text Available Studies in rats and mice have established that maternal nutrition induces epigenetic modifications, sometimes permanently, that alter gene expression in the fetus, which in turn leads to phenotypic changes. However, limited data is available on the influence of maternal diet on epigenetic modifications and gene expression in sheep. Therefore, the objectives of this study were to investigate the impact of different maternal dietary energy sources on the expression of imprinted genes in fetuses in sheep. Ewes were naturally bred to a single sire and from d 67 ± 3 of gestation until necropsy (d 130 ± 1, they were fed one of three diets of alfalfa haylage (HY; fiber, corn (CN; starch, or dried corn distiller’s grains (DG; fiber plus protein plus fat. A total of 26 fetuses were removed from the dams and longissimus dorsi, semitendinosus, perirenal adipose depot, and subcutaneous adipose depot tissues were collected for expression and DNA methylation analyses. Expression analysis of nine imprinted genes and three DNA methylatransferase (DNMTs genes showed significant effects of the different maternal diets on the expression of these genes. The methylation levels of CpG islands of both IGF2R and H19 were higher in HY and DG than CN fetuses in both males and females. This result is consistent with the low amino acid content of the CN diet, a source of methyl group donors, compared to HY and DG diets. Thus, results of this study provide evidence of association between maternal nutrition during pregnancy and transcriptomic and epigenomic alterations of imprinted genes and DNMTs in the fetal tissues.

  18. Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

    Directory of Open Access Journals (Sweden)

    E. Erhardt

    2006-12-01

    Full Text Available The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 µg/kg or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina but receiving recombinant leptin (rLeptin or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68 = 7.834, P = 0.007. There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34 = 3.751, P = 0.020 and exploration (F(3,34 = 3.581, P = 0.024. These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.

  19. Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Mónica Tramullas

    Full Text Available Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker protein expression in the prefrontal cortex (PFC and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption.

  20. Early cardiac changes induced by a hypercaloric Western-type diet in "subclinical" obesity.

    Science.gov (United States)

    Gonçalves, Nádia; Silva, Ana Filipa; Rodrigues, Patrícia Gonçalves; Correia, Eugénia; Moura, Cláudia; Eloy, Catarina; Roncon-Albuquerque, Roberto; Falcão-Pires, Inês; Leite-Moreira, Adelino F

    2016-03-15

    "Obesity cardiomyopathy" effects have been widely described; however, the specific contribution of metabolic changes and altered adipokine secretion are still uncharacterized. Moreover, a diagnosis based on body mass index might not be the most accurate to identify increased adiposity and its outcomes. In this study, we aimed to determine the impact of a Western-type diet [hypercaloric diet (HCD)] ingestion on biventricular structure and function, as well as the metabolic and endocrine changes that occur before the establishment of overt obesity. Wistar rats were fed for 6 wk with a regular diet or HCD. At the end of the protocol, metabolic tests, cardiac structure, and functional evaluation were performed, and blood and tissue samples collected to perform histological, molecular biology, and functional studies. The animals that ingested the HCD presented increased adiposity and larger adipocyte cross-sectional area, but similar body weight compared with the regular diet group. At the cardiac level, HCD induced biventricular cardiomyocyte hypertrophy, fibrosis, increased stiffness, and impaired relaxation. Galectin-3 plasma expression was likewise elevated in the same animals. The nutritional modulation also altered the secretory pattern of the adipose tissue, originating a proinflammatory systemic environment. In this study, we observed that before "clinical" overweight or frank obesity is established, the ingestion of a HCD-induced cardiac remodeling manifests by increased biventricular stiffness and diastolic dysfunction. The mechanism triggering the cardiac alterations appears to be the proinflammatory environment promoted by the adipose tissue dysfunction. Furthermore, galectin-3, a profibrotic molecule, might be a potential biomarker for the myocardial alterations promoted by the HCD before overweight or obesity. Copyright © 2016 the American Physiological Society.

  1. Hypothalamic Ventromedial Lin28a Enhances Glucose Metabolism in Diet-Induced Obesity.

    Science.gov (United States)

    Kim, Jung Dae; Toda, Chitoku; Ramírez, Cristina M; Fernández-Hernando, Carlos; Diano, Sabrina

    2017-08-01

    The Lin28a/Let-7 axis has been studied in peripheral tissues for its role in metabolism regulation. However, its central function remains unclear. Here we found that Lin28a is highly expressed in the hypothalamus compared with peripheral tissues. Its expression is positively correlated with positive energy balance, suggesting a potential central role for Lin28a in metabolism regulation. Thus, we targeted the hypothalamic ventromedial nucleus (VMH) to selectively overexpress (Lin28aKI(VMH) ) or downregulate (Lin28aKD(VMH) ) Lin28a expression in mice. With mice on a standard chow diet, body weight and glucose homeostasis were not affected in Lin28aKI(VMH) or Lin28aKD(VMH) mice. On a high-fat diet, although no differences in body weight and composition were observed, Lin28aKI(VMH) mice showed improved glucose tolerance and insulin sensitivity compared with controls. Conversely, Lin28aKD(VMH) mice displayed glucose intolerance and insulin resistance. Changes in VMH AKT activation of diet-induced obese Lin28aKI(VMH) or Lin28aKD(VMH) mice were not associated with alterations in Let-7 levels or insulin receptor activation. Rather, we observed altered expression of TANK-binding kinase-1 (TBK-1), which was found to be a direct Lin28a target mRNA. VMH-specific inhibition of TBK-1 in mice with diet-induced obesity impaired glucose metabolism and AKT activation. Altogether, our data show a TBK-1-dependent role for central Lin28a in glucose homeostasis. © 2017 by the American Diabetes Association.

  2. Labrador tea (Rhododendron groenlandicum) attenuates insulin resistance in a diet-induced obesity mouse model.

    Science.gov (United States)

    Ouchfoun, Meriem; Eid, Hoda M; Musallam, Lina; Brault, Antoine; Li, Shilin; Vallerand, Diane; Arnason, John T; Haddad, Pierre S

    2016-04-01

    Using a diet-induced obesity (DIO) mouse model, we investigated the antidiabetic effect of Labrador tea [Rhododendron groenlandicum (Oeder) Kron and Judd], a beverage and medicinal tea used by the Cree Nations of northern Quebec. C57BL6 mice were divided into five groups and given standard chow (~4 % of lipids) or high-fat diet (~35 % of lipids) for 8 weeks until they became obese and insulin resistant. Treatment began by adding the plant extract at three doses (125, 250 and 500 mg/kg) to the high-fat diet for another 8 weeks. At the end of the study, insulin-sensitive tissues (liver, skeletal muscle, adipose tissue) were collected to investigate the plant's molecular mechanisms. Labrador tea significantly reduced blood glucose (13 %), the response to an oral glucose tolerance test (18.2 %) and plasma insulin (65 %) while preventing hepatic steatosis (42 % reduction in hepatic triglyceride levels) in DIO mice. It stimulated insulin-dependent Akt pathway (55 %) and increased the expression of GLUT4 (53 %) in skeletal muscle. In the liver, Labrador tea stimulated the insulin-dependent Akt and the insulin-independent AMP-activated protein kinase pathways. The improvement in hepatic steatosis observed in DIO-treated mice was associated with a reduction in inflammation (through the IKK α/β) and a decrease in the hepatic content of SREBP-1 (39 %). Labrador tea exerts potential antidiabetic action by improving insulin sensitivity and mitigating high-fat diet-induced obesity and hyperglycemia. They validate the safety and efficacy of this plant, a promising candidate for culturally relevant complementary treatment in Cree diabetics.

  3. 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.

  4. Enzymatically synthesized glycogen reduces lipid accumulation in diet-induced obese rats.

    Science.gov (United States)

    Furuyashiki, Takashi; Ogawa, Rui; Nakayama, Yoko; Honda, Kazuhisa; Kamisoyama, Hiroshi; Takata, Hiroki; Yasuda, Michiko; Kuriki, Takashi; Ashida, Hitoshi

    2013-09-01

    Based on a recent study indicating that enzymatically synthesized glycogen (ESG) possesses a dietary, fiber-like action, we hypothesized that ESG can reduce the risk of obesity. In this study, the antiobesity effects of ESG were investigated in a model of diet-induced obesity. Male Sprague-Dawley rats were divided into 4 groups and fed a normal or high-fat diet, with or without 20% ESG, for 4 weeks. Body weight, food intake, lipid deposition in the white adipose tissues and liver, fecal lipid excretion, and plasma lipid profiles were measured. At week 3, the body fat mass was measured using an x-ray computed tomography system, which showed that ESG significantly suppressed the high-fat diet-induced lipid accumulation. Similar results were observed in the weight of the adipose tissue after the experiment. Moreover, ESG significantly suppressed the lipid accumulation in the liver but increased fecal lipid excretion. The plasma concentrations of triacylglycerol and nonesterified fatty acid were lowered after a high-fat diet, whereas the total bile acid concentration was increased by ESG. However, the hepatic messenger RNA (mRNA) levels of enzymes related to lipid metabolism were not affected by ESG. Conversely, the mRNA levels of long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase were up-regulated by ESG in the muscle. These results suggest that the combined effects of increased fecal lipid excretion, increased mRNA levels of enzymes that oxidize fatty acids in the muscle, and increased total bile acid concentration in the plasma mediate the inhibitory effect of ESG on lipid accumulation. © 2013.

  5. Metabolic effects of sleeve gastrectomy in female rat model of diet-induced obesity.

    Science.gov (United States)

    Brinckerhoff, Tatiana Z; Bondada, Sandhya; Lewis, Catherine E; French, Samuel W; DeUgarte, Daniel A

    2013-01-01

    Although women disproportionately undergo bariatric surgery, the rodent models investigating the mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients because it avoids the malabsorption associated with intestinal bypass. We sought to evaluate the effect of sleeve gastrectomy on young female rats with diet-induced obesity at the University of California, Los Angeles, David Geffen School of Medicine. Sprague-Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, the rats underwent either sleeve gastrectomy or sham surgery. The rats were killed 4 weeks after surgery. A chemistry panel was performed, and the serum adipokines and gut hormones were assayed. The homeostasis model assessment score was calculated. The liver histologic findings were graded for steatosis. The 2-sample t test was used to compare the results between the 2 groups. Sleeve gastrectomy was associated with significant weight loss (5% ± 6% versus -4% ± 6%; P resistance or steatohepatitis after 11 weeks of high-fat diet. Despite these limitations, additional gender-specific studies are warranted given that most bariatric surgeries are performed in women. Sleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin by way of mechanisms independent of ghrelin levels in a female model of diet-induced obesity. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  6. Resolvin E1 Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation Induced Atherogenesis

    Science.gov (United States)

    Hasturk, Hatice; Abdallah, Rima; Kantarci, Alpdogan; Nguyen, Daniel; Giordano, Nicholas; Hamilton, James; Van Dyke, Thomas E.

    2015-01-01

    Objective Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared to diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation. Approach and Results Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by P. gingivalis in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4μg/site or 0.4 μg/site) topically applied 3-times/ week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology and ex vivo MRI. Serum levels of C-reactive protein (CRP) were evaluated as a measure of systemic inflammation.RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis (pperiodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared to no-treatment (pperiodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events. PMID:25792445

  7. Diet-induced obesity associated with steatosis, oxidative stress, and inflammation in liver.

    Science.gov (United States)

    Peng, Yanhua; Rideout, Drew; Rakita, Steven; Lee, James; Murr, Michel

    2012-01-01

    Obesity induces steatosis and increases oxidative stress, as well as chronic inflammation in the liver. The balance between lipogenesis and lipolysis is disrupted in obese animals. At a cellular level, the changes in metabolic sensors and energy regulators are poorly understood. We hypothesized that diet-induced steatosis increases oxidative stress, inflammation, and changes the metabolic regulators to promote energy storage in mice. The setting was a university-affiliated basic science research laboratory. Four-week-old C57BL mice were fed a high-fat diet (n = 8) or regular chow (n = 8) for 7 weeks. The liver sections were stained for fat content and immunofluorescence. Liver homogenates were used for protein analysis by immunoblotting and mRNA analysis by reverse transcriptase-polymerase chain reaction. The gels were quantified using densitometry P ≤ .05 was considered significant. The high-fat diet upregulated protein kinase-C atypical isoforms ζ and λ and decreased glucose tolerance and the interaction of insulin receptor substrate 2 with phosphoinositide kinase-3. The high-fat diet increased the transcriptional factors liver X receptor (4321 ± 98 versus 2981 ± 80) and carbohydrate response element-binding protein (5132 ± 135 versus 3076 ± 91), the lipogenesis genes fatty acid binding protein 5, stearoyl-co-enzyme A desaturase-1, and acetyl-co-enzyme A carboxylase protein, and fatty acid synthesis. The high-fat diet decreased 5'-adenosine monophosphate-activated protein kinase (2561 ± 78 versus 1765 ± 65), glucokinase-3β (2.214 ± 34 versus 3356 ± 86), and SIRT1 (2015 ± 76 versus 3567 ± 104) and increased tumor necrosis factor-α (3415 ± 112 versus 2042 ± 65), nuclear factor kappa B (5123 ± 201 versus 2562 ± 103), cyclooxygenase-2 (4230 ± 113 versus 2473 ± 98), nicotinamide-adenine dinucleotide phosphate oxidase (3501 ± 106 versus 1600 ± 69) and reactive oxygen species production (all P obese mice versus lean mice). A high-fat diet impairs

  8. Predictors of Diet-Induced Weight Loss in Overweight Adults with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Kirsten A Berk

    Full Text Available A very low calorie diet improves the metabolic regulation of obesity related type 2 diabetes, but not for all patients, which leads to frustration in patients and professionals alike. The aim of this study was to develop a prediction model of diet-induced weight loss in type 2 diabetes.192 patients with type 2 diabetes and BMI>27 kg/m2 from the outpatient diabetes clinic of the Erasmus Medical Center underwent an 8-week very low calorie diet. Baseline demographic, psychological and physiological parameters were measured and the C-index was calculated of the model with the largest explained variance of relative weight loss using backward linear regression analysis. The model was internally validated using bootstrapping techniques.Weight loss after the diet was 7.8±4.6 kg (95%CI 7.2-8.5; p<0.001 and was independently associated with the baseline variables fasting glucose (B = -0.33 (95%CI -0.49, -0.18, p = 0.001, anxiety (HADS; B = -0.22 (95%CI -0.34, -0.11, p = 0.001, numb feeling in extremities (B = 1.86 (95%CI 0.85, 2.87, p = 0.002, insulin dose (B = 0.01 (95%CI 0.00, 0.02, p = 0.014 and waist-to-hip ratio (B = 6.79 (95%CI 2.10, 11.78, p = 0.003. This model explained 25% of the variance in weight loss. The C-index of this model to predict successful (≥5% weight loss was 0.74 (95%CI 0.67-0.82, with a sensitivity of 0.93 (95% CI 0.89-0.97 and specificity of 0.29 (95% CI 0.16-0.42. When only the obese T2D patients (BMI≥30 kg/m2; n = 181 were considered, age also contributed to the model (B = 0.06 (95%CI 0.02, 0.11, p = 0.008, whereas waist-to-hip ratio did not.Diet-induced weight loss in overweight adults with T2D was predicted by five baseline parameters, which were predominantly diabetes related. However, failure seems difficult to predict. We propose to test this prediction model in future prospective diet intervention studies in patients with type 2 diabetes.

  9. Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

    Science.gov (United States)

    Cook, Jason B; Hendrickson, Linzy M; Garwood, Grant M; Toungate, Kelsey M; Nania, Christina V; Morikawa, Hitoshi

    2017-01-01

    Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3-4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity.

  10. Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking

    Science.gov (United States)

    Hendrickson, Linzy M.; Garwood, Grant M.; Toungate, Kelsey M.; Nania, Christina V.; Morikawa, Hitoshi

    2017-01-01

    Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3–4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity. PMID:28859110

  11. SOCS-1 deficiency does not prevent diet-induced insulin resistance

    DEFF Research Database (Denmark)

    Emanuelli, Brice; Macotela, Yazmin; Boucher, Jérémie

    2008-01-01

    Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling. Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance. Using SOCS-1 knockout mice, we...... investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD). SOCS-1 knockout mice on HFD gained 70% more weight, displayed a 2.3-fold increase in epididymal fat pads mass and increased hepatic lipid content. This was accompanied by increased mRNA expression...... of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver. HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests. Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency...

  12. The effects of fatty acid composition on cardiac hypertrophy and function in mouse models of diet-induced obesity.

    Science.gov (United States)

    Nguyen, Son; Shao, Dan; Tomasi, Loreta C; Braun, Alyssa; de Mattos, Ana Barbosa Marcondes; Choi, Yong Seon; Villet, Outi; Roe, Nathan; Halterman, Carliana R; Tian, Rong; Kolwicz, Stephen C

    2017-08-01

    High-fat diets (HFDs) are used frequently to study the development of cardiac dysfunction in animal models of obesity and diabetes. However, impairment in systolic function, often reported as declining ejection fraction, may not consistently occur in a given time frame which could be contributable to a variety of factors within the experimental design. One major factor may be the amounts of saturated and unsaturated fatty acids (FAs) that are present in the diet. To determine whether the FA content and composition were critical determinants in the development of cardiac dysfunction in response to high-fat feeding, we fed adult, male mice Western diet (45% fat, 60% saturated), Surwit diet (60% fat, 90% saturated), milk-fat-based diet (60% fat, 60% saturated) or high-fat Western diet (HFWD, 60% fat, 32% saturated) for 12 weeks. We report that neither the amount of total fat nor the ratio of saturated to unsaturated FAs in the diets differentially affects body weight and adiposity in mice. In addition, no evidence of systolic dysfunction is present after 12 weeks. Interestingly, the HFWD, with equal parts saturated, monounsaturated and polyunsaturated FAs, induces mild cardiac hypertrophy and diastolic dysfunction after 12 weeks, which coincides with elevated serum levels of arachidonic acid. Our results suggest that the dietary FA content and composition may be a primary determinant of diastolic, but not systolic, dysfunction in animal models of diet-induced obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Geraniol attenuates oxidative stress by Nrf2 activation in diet-induced experimental atherosclerosis.

    Science.gov (United States)

    Jayachandran, Muthukumaran; Chandrasekaran, Balaji; Namasivayam, Nalini

    2015-07-01

    Preclinical and clinical studies suggest the use of antioxidants as an effective measure to reduce the progression of oxidative-stress-related disorders. Nuclear factor E2-related factor 2 (Nrf2) is a key component to cellular redox homeostasis in the attenuation of oxidative-stress-associated pathological processes. The objective of the current study was to evaluate the role of geraniol (GOH) in preserving the plasma lipid status, endothelial function, antioxidant status, and inhibition of lipid peroxidation (LPO) in hamsters fed an atherogenic diet (AD). Male Syrian hamsters were randomly grouped into four groups: group 1 was control animals; group 2 was animals fed GOH alone (100 mg/kg bw po); group 3 was animals fed AD (standard pellet diet+10% coconut oil+0.25% cholesterol+0.25% cholic acid); and group 4 was fed AD+GOH (100 mg/kg bw) for 12 weeks. At the end of the feeding period, the animals were sacrificed and the liver, heart, and aorta from each group were analyzed for antioxidants, LPO markers, and histological changes. AD feeding induced a significant change in lipid profile, endothelial function marker, activities of the antioxidant enzymes, alterations in the LPO markers, Nrf2 expression, and equally significant changes in the organ histology. Supplementation with GOH appreciably prevented the alterations induced by the AD on all the above parameters. Thus, GOH offers marked protection against AD-induced abnormalities.

  14. PDGFRβ Regulates Adipose Tissue Expansion and Glucose Metabolism via Vascular Remodeling in Diet-Induced Obesity.

    Science.gov (United States)

    Onogi, Yasuhiro; Wada, Tsutomu; Kamiya, Chie; Inata, Kento; Matsuzawa, Takatoshi; Inaba, Yuka; Kimura, Kumi; Inoue, Hiroshi; Yamamoto, Seiji; Ishii, Yoko; Koya, Daisuke; Tsuneki, Hiroshi; Sasahara, Masakiyo; Sasaoka, Toshiyasu

    2017-04-01

    Platelet-derived growth factor (PDGF) is a key factor in angiogenesis; however, its role in adult obesity remains unclear. In order to clarify its pathophysiological role, we investigated the significance of PDGF receptor β (PDGFRβ) in adipose tissue expansion and glucose metabolism. Mature vessels in the epididymal white adipose tissue (eWAT) were tightly wrapped with pericytes in normal mice. Pericyte desorption from vessels and the subsequent proliferation of endothelial cells were markedly increased in the eWAT of diet-induced obese mice. Analyses with flow cytometry and adipose tissue cultures indicated that PDGF-B caused the detachment of pericytes from vessels in a concentration-dependent manner. M1-macrophages were a major type of cells expressing PDGF-B in obese adipose tissue. In contrast, pericyte detachment was attenuated and vascularity within eWAT was reduced in tamoxifen-inducible conditional Pdgfrb-knockout mice with decreases in adipocyte size and chronic inflammation. Furthermore, Pdgfrb-knockout mice showed enhanced energy expenditure. Consequently, diet-induced obesity and the associated deterioration of glucose metabolism in wild-type mice were absent in Pdgfrb-knockout mice. Therefore, PDGF-B-PDGFRβ signaling plays a significant role in the development of adipose tissue neovascularization and appears to be a fundamental target for the prevention of obesity and type 2 diabetes. © 2017 by the American Diabetes Association.

  15. High-fat high-sugar diet induces polycystic ovary syndrome in a rodent model.

    Science.gov (United States)

    Roberts, Jacob S; Perets, Ron A; Sarfert, Kathryn S; Bowman, John J; Ozark, Patrick A; Whitworth, Gregg B; Blythe, Sarah N; Toporikova, Natalia

    2017-01-27

    Obesity has been linked with a host of metabolic and reproductive disorders including polycystic ovary syndrome (PCOS). While a clear association exists between obesity and PCOS, the exact nature of this relationship remains unexplained. The primary symptoms of PCOS include hyperandrogenism, anovulation, and polycystic ovaries. Most animal models utilize androgen treatments to induce PCOS. However, these models often fail to address the underlying causes of the disease and do not effectively reproduce key metabolic features such as hyperinsulinemia. Here, we present a novel rodent model of diet-induced obesity that recapitulates both the metabolic and reproductive phenotypes of human PCOS. Rats on a high-fat high-sugar (HFHS) diet not only demonstrated signs of metabolic impairment, but they also developed polycystic ovaries and experienced irregular estrous cycling. Though hyperandrogenism was not characteristic of HFHS animals as a group, elevated testosterone levels were predictive of high numbers of ovarian cysts. Alterations in steroidogenesis and folliculogenesis gene expression were also found via RNA sequencing of ovarian tissue. Importantly, the PCOS-like symptoms induced in these rats may share a similar etiology to PCOS in humans. Therefore, this model offers a unique opportunity to study PCOS at its genesis rather than following the development of disease symptoms.

  16. Inhibiting Adipose Tissue Lipogenesis Reprograms Thermogenesis and PPARγ Activation to Decrease Diet-induced Obesity

    Science.gov (United States)

    Lodhi, Irfan J.; Yin, Li; Jensen-Urstad, Anne P. L.; Funai, Katsuhiko; Coleman, Trey; Baird, John H.; El Ramahi, Meral K.; Razani, Babak; Song, Haowei; Fu-Hsu, Fong; Turk, John; Semenkovich, Clay F.

    2012-01-01

    SUMMARY De novo lipogenesis in adipocytes, especially with high fat feeding, is poorly understood. We demonstrate that an adipocyte lipogenic pathway encompassing fatty acid synthase (FAS) and PexRAP (Peroxisomal Reductase Activating PPARγ) modulates endogenous PPARγ activation and adiposity. Mice lacking FAS in adult adipose tissue manifested increased energy expenditure, increased brown fat-like adipocytes in subcutaneous adipose tissue, and resistance to diet-induced obesity. FAS knockdown in embryonic fibroblasts decreased PPARγ transcriptional activity and adipogenesis. FAS-dependent alkyl ether phosphatidylcholine species were associated with PPARγ and treatment of 3T3-L1 cells with one such ether lipid increased PPARγ transcriptional activity. PexRAP, a protein required for alkyl ether lipid synthesis, was associated with peroxisomes and induced during adipogenesis. PexRAP knockdown in cells decreased PPARγ transcriptional activity and adipogenesis. PexRAP knockdown in mice decreased expression of PPARγ–dependent genes and reduced diet-induced adiposity. These findings suggest that inhibiting PexRAP or related lipogenic enzymes could treat obesity and diabetes. PMID:22863804

  17. Renoprotective effect of virgin coconut oil in heated palm oil diet-induced hypertensive rats.

    Science.gov (United States)

    Kamisah, Yusof; Ang, Shu-Min; Othman, Faizah; Nurul-Iman, Badlishah Sham; Qodriyah, Hj Mohd Saad

    2016-10-01

    Virgin coconut oil, rich in antioxidants, was shown to attenuate hypertension. This study aimed to investigate the effects of virgin coconut oil on blood pressure and related parameters in kidneys in rats fed with 5-times-heated palm oil (5HPO). Thirty-two male Sprague-Dawley rats were divided into 4 groups. Two groups were fed 5HPO (15%) diet and the second group was also given virgin coconut oil (1.42 mL/kg, oral) daily for 16 weeks. The other 2 groups were given basal diet without (control) and with virgin coconut oil. Systolic blood pressure was measured pre- and post-treatment. After 16 weeks, the rats were sacrificed and kidneys were harvested. Dietary 5HPO increased blood pressure, renal thiobarbituric acid reactive substance (TBARS), and nitric oxide contents, but decreased heme oxygenase activity. Virgin coconut oil prevented increase in 5HPO-induced blood pressure and renal nitric oxide content as well as the decrease in renal heme oxygenase activity. The virgin coconut oil also reduced the elevation of renal TBARS induced by the heated oil. However, neither dietary 5HPO nor virgin coconut oil affected renal histomorphometry. In conclusion, virgin coconut oil has a potential to reduce the development of hypertension and renal injury induced by dietary heated oil, possibly via its antioxidant protective effects on the kidneys.

  18. Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

    Science.gov (United States)

    Kim, Sung-Bae; Kang, Ok-Hwa; Lee, Young-Seob; Han, Sin-Hee; Ahn, Young-Sup; Cha, Seon-Woo; Seo, Yun-Soo; Kong, Ryong; Kwon, Dong-Yeul

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD.

  19. Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

    Directory of Open Access Journals (Sweden)

    Sung-Bae Kim

    Full Text Available Nonalcoholic fatty liver disease (NAFLD, the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment, MCD diet (MCD diet only, MCD + silymarin (SIL 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent

  20. New insights into the effects of onion consumption on lipid mediators using a diet-induced model of hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Diana González-Peña

    2017-04-01

    Full Text Available The levels and roles of lipid mediators can be modified in response to nutritional stimuli. The aim of this study was to investigate shifts in oxylipin and sphingolipid profiles stimulated by a hypercholesterolemic (HC diet along with the modulating effects of onion introduced as an antioxidant functional ingredient characterized in the diet (HCO. Oxylipin and sphingolipid profiles were determined in plasma and tissues from Wistar rats using LC-MS/MS. Plasma ω-3 and ω-6 PUFA-derived oxylipins decreased in rats after 7 weeks of HC feeding, but did not evidence a further shift with HCO diet. Onion ingredient supplementation modulated the hepatic concentrations of prostaglandins and enhanced ω-3 oxylipins in the liver of HCO-fed rats relative to the HC group. The HC diet induced shifts in plasma sphingolipids, increasing sphingoid bases, dihydroceramides and ceramides, whilst the sphingomyelin, hexosylceramide and lactosylceramide families decreased. The HCO diet modified some HC diet-induced changes in sphingolipids in liver and spleen tissue. Onion supplementation effected changes in lipid mediator levels in diet-induced hypercholesterolemic Wistar rats. The potential of onion as regulator of pro-inflammatory mediators, and possible enhancer of pro-resolution pathways, warrants further study of the interaction of functional ingredients with bioactive lipid mediators and their potential impact on inflammation, oxidative stress and organ dysfunction.

  1. New insights into the effects of onion consumption on lipid mediators using a diet-induced model of hypercholesterolemia.

    Science.gov (United States)

    González-Peña, Diana; Checa, Antonio; de Ancos, Begoña; Wheelock, Craig E; Sánchez-Moreno, Concepción

    2017-04-01

    The levels and roles of lipid mediators can be modified in response to nutritional stimuli. The aim of this study was to investigate shifts in oxylipin and sphingolipid profiles stimulated by a hypercholesterolemic (HC) diet along with the modulating effects of onion introduced as an antioxidant functional ingredient characterized in the diet (HCO). Oxylipin and sphingolipid profiles were determined in plasma and tissues from Wistar rats using LC-MS/MS. Plasma ω-3 and ω-6 PUFA-derived oxylipins decreased in rats after 7 weeks of HC feeding, but did not evidence a further shift with HCO diet. Onion ingredient supplementation modulated the hepatic concentrations of prostaglandins and enhanced ω-3 oxylipins in the liver of HCO-fed rats relative to the HC group. The HC diet induced shifts in plasma sphingolipids, increasing sphingoid bases, dihydroceramides and ceramides, whilst the sphingomyelin, hexosylceramide and lactosylceramide families decreased. The HCO diet modified some HC diet-induced changes in sphingolipids in liver and spleen tissue. Onion supplementation effected changes in lipid mediator levels in diet-induced hypercholesterolemic Wistar rats. The potential of onion as regulator of pro-inflammatory mediators, and possible enhancer of pro-resolution pathways, warrants further study of the interaction of functional ingredients with bioactive lipid mediators and their potential impact on inflammation, oxidative stress and organ dysfunction. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Linarin Enriched Extract Attenuates Liver Injury and Inflammation Induced by High-Fat High-Cholesterol Diet in Rats

    Directory of Open Access Journals (Sweden)

    Zhen-Jie Zhuang

    2017-01-01

    Full Text Available The aim of this study was to explore the potential beneficial effects of linarin enriched Flos Chrysanthemi extract (Lin-extract on nonalcoholic steatohepatitis (NASH induced by high-fat high-cholesterol (HFHC diet in rats. SD rats received normal diet, HFHC diet, or HFHC diet plus different doses of Lin-extract. The liver content of triglyceride and total cholesterol markedly increased in HFHC diet-fed model rats while middle and high dose of Lin-extract lowered liver cholesterol significantly. The expression of stearoyl-CoA desaturase (SCD1 was upregulated by HFHC diet and further elevated by high dose Lin-extract. High dose of Lin-extract also markedly lowered the serum alanine aminotransferase (ALT and aspartate aminotransferase (AST and inhibited the activation of c-Jun N-terminal kinase (JNK induced by HFHC in livers. The HFHC-increased mRNA levels of hepatic inflammation cytokines, including monocyte chemotactic protein-1 (MCP-1, tumor necrosis factor-α (TNF-α, and chemokine (C-X-C motif ligand 1 (CXCL1, were suppressed by Lin-extract dose-dependently. Furthermore, pathology evaluation showed that high dose Lin-extract greatly improved lobular inflammation. Our results suggest that Lin-extract could attenuate liver injury and inflammation induced by HFHC diet in rats. Its modulatory effect on lipid metabolism may partially contribute to this protective effect.

  3. Genetic variability to diet-induced hippocampal dysfunction in BXD recombinant inbred (RI) mouse strains.

    Science.gov (United States)

    Xue, Yueqiang; Li, JingJing; Yan, Lei; Lu, Lu; Liao, Francesca-Fang

    2015-10-01

    Evidence has emerged suggesting that diet-induced obesity can have a negative effect on cognitive function. Here, we exploited a mouse genetic reference population to look for the linkage between these two processes on a genome-wide scale. The focus of this report is to determine whether the various BXD RI strains exhibited different behavioral performance and hippocampal function under high fat dietary (HFD) condition. We quantified genetic variation in body weight gain and consequent influences on behavioral tests in a cohort of 14 BXD strains of mice (8-12 mice/strain, n = 153), for which we have matched data on gene expression and neuroanatomical changes in the hippocampus. It showed that BXD66 was the most susceptible, whereas BXD77 was the least susceptible strain to dietary influences. The performance of spatial reference memory tasks was strongly correlated with body weight gain (P < 0.05). The obesity-prone strains displayed more pronounced spatial memory defects compared to the obesity-resistant strains. These abnormalities were associated with neuroinflammation, synaptic dysfunction, and neuronal loss in the hippocampus. The biological relevance of DSCAM gene polymorphism was assessed using the trait correlation analysis tool in Genenetwork. Furthermore, a significant strain-dependent gene expression difference of DSCAM was detected in the hippocampus of obese BXD strains by real-time quantitative PCR. In conclusion, a variety of across-strain hippocampal alterations and genetic predispositions to diet-induced obesity were found in a set of BXD strains. The obesity-prone and obesity-resistant lines we have identified should be highly useful to study the molecular genetics of diet-induced cognitive decline. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice.

    Science.gov (United States)

    Rosa-Caldwell, Megan E; Lee, David E; Brown, Jacob L; Brown, Lemuel A; Perry, Richard A; Greene, Elizabeth S; Carvallo Chaigneau, Francisco R; Washington, Tyrone A; Greene, Nicholas P

    2017-02-01

    Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis and is associated with degeneration of the mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose of this study was to investigate regulation of mitochondrial and autophagy quality control in liver following Western diet-induced obesity and voluntary physical activity. Eight-week-old C57BL/6J mice were fed a Western diet (WD) or normal chow (NC, control) for 4 weeks; afterwards, groups were divided into voluntary wheel running (VWR) or sedentary (SED) conditions for an additional 4 weeks. WD-SED animals had a median histology score of 2, whereas WD-VWR was not different from NC groups (median score 1). There was no difference in mRNA of inflammatory markers Il6 and Tnfa in WD animals. WD animals had 50% lower mitochondrial content (COX IV and Cytochrome C proteins), 50% lower Pgc1a mRNA content, and reduced content of mitochondrial fusion and fission markers. Markers of autophagy were increased in VWR animals, regardless of obesity, as measured by 50% greater LC3-II/I ratio and 40% lower p62 protein content. BNIP3 protein content was 30% less in WD animals compared with NC animals, regardless of physical activity. Diet-induced obesity results in derangements in mitochondrial quality control that appear to occur prior to the onset of hepatic inflammation. Moderate physical activity appears to enhance basal autophagy in the liver; increased autophagy may provide protection from hepatic fat accumulation.

  5. Intrarenal ghrelin receptor antagonism prevents high-fat diet-induced hypertension in male rats.

    Science.gov (United States)

    Kemp, Brandon A; Howell, Nancy L; Gildea, John J; Padia, Shetal H

    2014-07-01

    Excess weight gain contributes up to 65% of the risk of primary hypertension, and the increase in blood pressure in response to high-fat diet (HFD) is preceded by significant increases in renal tubular sodium (Na(+)) reabsorption. In normal rats, intrarenal ghrelin infusion increases distal nephron-dependent Na(+) reabsorption via activation of the intrarenal ghrelin receptor (GHSR). This study focusses on the role of intrarenal GHSR-mediated Na(+) reabsorption in HFD-induced hypertension. Dahl salt-sensitive rats received standard diet or HFD for 6 weeks. Rats underwent uninephrectomy and osmotic minipump implantation for chronic intrarenal delivery of vehicle (0.25 μL/h × 28 d), selective GHSR antagonist [D-Lys-3]-growth hormone releasing peptide-6 (0.2μM/d), or GHSR inverse agonist [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P (SUB-P) (3.6μM/d). HFD rats with vehicle pumps had significantly increased renal GHSR expression compared with standard diet (0.092 ± 0.005 vs 0.065 ± 0.004 arbitrary units; P ghrelin levels were similar (16.3±6.2 vs 15.7±8.7 pg/g tissue). HFD rats with vehicle pumps became hypertensive after 2 weeks (P ghrelin-dependent, activity of the GHSR, and HFD-induced α-epithelial Na(+) channel up-regulation was abolished during GHSR antagonism, these data suggest that HFD increases the constitutive activity of renal GHSR to increase Na(+) reabsorption and induce hypertension in rats.

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

    OpenAIRE

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

    2016-01-01

    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)-induc...

  7. Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

    Science.gov (United States)

    Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

    2015-03-18

    Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright

  8. Diet-induced weight loss and exercise alone and in combination enhance the expression of adiponectin receptors in adipose tissue and skeletal muscle, but only diet-induced weight loss enhanced circulating adiponectin

    DEFF Research Database (Denmark)

    Christiansen, Tore; Paulsen, Søren K; Bruun, Jens M

    2009-01-01

    by the intervention. Conclusion: Exercise alone and in combination with a diet-induced weight loss enhance the mRNA expression of adiponectin receptors in AT and in SM but only a pronounced hypocaloric-induced weight-loss increases circulating adiponectin in obese subjects.......Objective: The aim of the study was to investigate the effect of weight loss and exercise independently and in combination on circulating levels of adiponectin including low molecular weight, medium molecular weight, and high molecular weight adiponectin and expression of adiponectin...... and adiponectin receptors (AdipoR) in adipose tissue (AT) and skeletal muscle (SM). Design and Methods: Seventy-nine obese males and females were randomized into the following: 1) exercise only (12 wk of exercise without diet restriction); 2) hypocaloric diet [8 wk of very low energy diet (600 kcal/d) followed...

  9. 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.

  10. Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.

    Science.gov (United States)

    Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kosuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

    2017-07-01

    Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Teucrium polium reversed the MCD diet-induced liver injury in rats.

    Science.gov (United States)

    Amini, Rahim; Yazdanparast, Razieh; Aghazadeh, Safiyeh; Ghaffari, Seyed H

    2011-09-01

    In the present study, we evaluated the ability of Teucrium polium ethyl acetate fraction, with high antioxidant activity, in the treatment of nonalcoholic steatohepatitis (NASH) in rats and its possible effect on factors involved in pathogenesis of the disease. To induce NASH, a methionine and choline deficient (MCD) diet was given to N-Mary rats for 8 weeks. After NASH development, MCD-fed rats were divided into 2 groups: NASH group that received MCD diet and NASH + T group which was fed MCD diet plus ethyl acetate fraction of T. polium orally for 3 weeks. Histopathological evaluations revealed that treatment with the extract has abated the severity of NASH among the MCD-fed rats. In addition, the fraction reduced the elevated levels of hepatic tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) gene expression and also the elevated level of malondialdehyde (MDA). In addition, the extract increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and enhanced the level of hepatic glutathione (GSH). Moreover, the fraction treatments lowered caspase-3 level and the phosphorylated form of C-Jun N-terminal kinase (JNK) and augmented the phosphorylated level of extracellular regulated kinase1/2 (ERK1/2). These results indicate that the ethyl acetate fraction of T. poium effectively reversed NASH, mainly due to its strong antioxidant and anti-inflammatory properties.

  12. High-fat diet induced isoform changes of the Parkinson's disease protein DJ-1.

    Science.gov (United States)

    Poschmann, Gereon; Seyfarth, Katrin; Besong Agbo, Daniela; Klafki, Hans-Wolfgang; Rozman, Jan; Wurst, Wolfgang; Wiltfang, Jens; Meyer, Helmut E; Klingenspor, Martin; Stühler, Kai

    2014-05-02

    Genetic and environmental factors mediate via different physiological and molecular processes a shifted energy balance leading to overweight and obesity. To get insights into the underlying processes involved in energy intake and weight gain, we compared hypothalamic tissue of mice kept on a high-fat or control diet for 10 days by a proteomic approach. Using two-dimensional difference gel electrophoresis in combination with LC-MS/MS, we observed significant abundance changes in 15 protein spots. One isoform of the protein DJ-1 was elevated in the high-fat diet group in three different mouse strains SWR/J, C57BL/6N, and AKR/J analyzed. Large-scale validation of DJ-1 isoforms in individual samples and tissues confirmed a shift in the pattern of DJ-1 isoforms toward more acidic isoforms in several brain and peripheral tissues after feeding a high-fat diet for 10 days. The identification of oxidation of cysteine 106 as well as 2-succinyl modification of the same residue by mass spectrometry not only explains the isoelectric shift of DJ-1 but also links our results to similar shifts of DJ-1 observed in neurodegenerative disease states under oxidative stress. We hypothesize that DJ-1 is a common physiological sensor involved in both nutrition-induced effects and neurodegenerative disease states.

  13. Fat and cholesterol diet induced lipid metabolic disorders and insulin resistance in rabbit.

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    Zheng, H; Zhang, C; Yang, W; Wang, Y; Lin, Y; Yang, P; Yu, Q; Fan, J; Liu, E

    2009-09-01

    Lipid disorder has been found to result in insulin resistance (IR). IR often is associated with other cardiovascular risk factors. However, the pathogenesis of human IR is not completely understood. The present study was designed to examine if rabbits were fed with a diet containing high fat and high-cholesterol diet (HFCD) could develop lipid disorder and subsequently IR. Male Japanese white rabbits were fed either a normal chow diet or HFCD for 20 weeks. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose, and insulin were measured. To evaluate glucose metabolism, we performed an intravenous glucose tolerance test. In addition, we compared adipose tissue accumulation and aortic atherosclerosis lesions in HFCD-fed rabbits with those in control rabbits. In HFCD-fed rabbits there was an increase in plasma levels of TC and TG as well as visceral adipose tissue accumulation. Severe aortic atherosclerotic lesions were found in HFCD-fed rabbits. Although there were no differences in body weight, plasma insulin and blood pressure between the two groups, HFCD-fed rabbits showed higher insulin IR index compared to control rabbits. Our results showed that HFCD induced IR, increased adipose accumulation and atherosclerotic lesions in rabbits, suggesting that the HFCD-fed rabbits can serve as a model for the research on human IR and lipid metabolism abnormalities. J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart.New York.

  14. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease.

    Science.gov (United States)

    Brown, Kirsty; DeCoffe, Daniella; Molcan, Erin; Gibson, Deanna L

    2012-08-01

    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.

  15. Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity.

    Science.gov (United States)

    Zlotnikov, Nataliya; Javid, Ashkan; Ahmed, Mijhgan; Eshghi, Azad; Tang, Tian Tian; Arya, Anoop; Bansal, Anil; Matar, Fatima; Parikh, Maitry; Ebady, Rhodaba; Koh, Adeline; Gupta, Nupur; Song, Peng; Zhang, Yang; Newbigging, Susan; Wormser, Gary P; Schwartz, Ira; Inman, Robert; Glogauer, Michael; Moriarty, Tara J

    2017-05-01

    Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

  16. Tea polyphenols ameliorate fat storage induced by high-fat diet in Drosophila melanogaster.

    Science.gov (United States)

    Kayashima, Yasunari; Murata, Shinichi; Sato, Misaki; Matsuura, Kanako; Asanuma, Toshimichi; Chimoto, Junko; Ishii, Takeshi; Mochizuki, Kazuo; Kumazawa, Shigenori; Nakayama, Tsutomu; Yamakawa-Kobayashi, Kimiko

    2015-12-01

    Polyphenols in tea are considered beneficial to human health. However, many such claims of their bioactivity still require in vitro and in vivo evidence. Using Drosophila melanogaster as a model multicellular organism, we assess the fat accumulation-suppressing effects of theaflavin (TF), a tea polyphenol; epitheaflagallin (ETG), which has an unknown function; and epigallocatechin gallate (EGCg), a prominent component of green tea. Dietary TF reduced the malondialdehyde accumulation related to a high-fat diet in adult flies. Other physiological and genetic responses induced by the high-fat diet, such as lipid accumulation in the fat body and expression of lipid metabolism-related genes, were ameliorated by the addition of TF, ETG, and EGCg, in some cases approaching respective levels without high-fat diet exposure. Continuous ingestion of the three polyphenols resulted in a shortened lifespan. We provide evidence in Drosophila that tea polyphenols have a fat accumulation-suppressing effect that has received recent attention. We also suggest that tea polyphenols can provide different desirable biological activities depending on their composition and the presence or absence of other chemical components.

  17. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.

    Science.gov (United States)

    Fagman, Johan B; Wilhelmson, Anna S; Motta, Benedetta M; Pirazzi, Carlo; Alexanderson, Camilla; De Gendt, Karel; Verhoeven, Guido; Holmäng, Agneta; Anesten, Fredrik; Jansson, John-Olov; Levin, Malin; Borén, Jan; Ohlsson, Claes; Krettek, Alexandra; Romeo, Stefano; Tivesten, Åsa

    2015-04-01

    Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)-dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)-deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (-41%; thoracic aorta), subcutaneous fat mass (-44%), and cholesterol levels (-35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism. © FASEB.

  18. High Fat Diet Induces Adhesion of Platelets to Endothelium in Two Models of Dyslipidemia

    Science.gov (United States)

    Gonzalez, Jaime; Donoso, Wendy; Díaz, Natalia; Albornoz, María Eliana; Huilcaman, Ricardo; Morales, Erik

    2014-01-01

    Cardiovascular diseases (CVD) represent about 30% of all global deaths. It is currently accepted that, in the atherogenic process, platelets play an important role, contributing to endothelial activation and modulation of the inflammatory phenomenon, promoting the beginning and formation of lesions and their subsequent thrombotic complications. The objective of the present work was to study using immunohistochemistry, the presence of platelets, monocytes/macrophages, and cell adhesion molecules (CD61, CD163, and CD54), in two stages of the atheromatous process. CF-1 mice fed a fat diet were used to obtain early stages of atheromatous process, denominated early stage of atherosclerosis, and ApoE−/− mice fed a fat diet were used to observe advanced stages of atherosclerosis. The CF-1 mice model presented immunostaining on endothelial surface for all three markers studied; the advanced atherosclerosis model in ApoE−/− mice also presented granular immunostaining on lesion thickness, for the same markers. These results suggest that platelets participate in atheromatous process from early stages to advance d stages. High fat diet induces adhesion of platelets to endothelial cells in vivo. These findings support studying the participation of platelets in the formation of atheromatous plate. PMID:25328689

  19. Exercise protects against high-fat diet-induced hypothalamic inflammation.

    Science.gov (United States)

    Yi, Chun-Xia; Al-Massadi, Omar; Donelan, Elizabeth; Lehti, Maarit; Weber, Jon; Ress, Chandler; Trivedi, Chitrang; Müller, Timo D; Woods, Stephen C; Hofmann, Susanna M

    2012-06-25

    Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing local production of specific interleukins and cytokines, and these in turn may further promote systemic metabolic disease. Whether or how this microglial activation can be averted or reversed is unknown. Since running exercise improves systemic metabolic health and has been found to promote neuronal survival as well as the recovery of brain functions after injury, we hypothesized that regular treadmill running may blunt the effect of western diet on hypothalamic inflammation. Using low-density lipoprotein receptor deficient (l dlr-/-) mice to better reflect human lipid metabolism, we first confirmed that microglial activation in the hypothalamus is severely increased upon exposure to a high-fat, or "western", diet. Moderate, but regular, treadmill running exercise markedly decreased hypothalamic inflammation in these mice. Furthermore, the observed decline in microglial activation was associated with an improvement of glucose tolerance. Our findings support the hypothesis that hypothalamic inflammation can be reversed by exercise and suggest that interventions to avert or reverse neuronal damage may offer relevant potential in obesity treatment and prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. An obligate role of oxytocin neurons in diet induced energy expenditure.

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    Zhaofei Wu

    Full Text Available Oxytocin neurons represent one of the major subsets of neurons in the paraventricular hypothalamus (PVH, a critical brain region for energy homeostasis. Despite substantial evidence supporting a role of oxytocin in body weight regulation, it remains controversial whether oxytocin neurons directly regulate body weight homeostasis, feeding or energy expenditure. Pharmacologic doses of oxytocin suppress feeding through a proposed melanocortin responsive projection from the PVH to the hindbrain. In contrast, deficiency in oxytocin or its receptor leads to reduced energy expenditure without feeding abnormalities. To test the physiological function of oxytocin neurons, we specifically ablated oxytocin neurons in adult mice. Our results show that oxytocin neuron ablation in adult animals has no effect on body weight, food intake or energy expenditure on a regular diet. Interestingly, male mice lacking oxytocin neurons are more sensitive to high fat diet-induced obesity due solely to reduced energy expenditure. In addition, despite a normal food intake, these mice exhibit a blunted food intake response to leptin administration. Thus, our study suggests that oxytocin neurons are required to resist the obesity associated with a high fat diet; but their role in feeding is permissive and can be compensated for by redundant pathways.

  1. Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats

    Directory of Open Access Journals (Sweden)

    Tian Ya-ping

    2010-07-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD, which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms. Results High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin, which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways. Conclusions Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.

  2. Centrally administered urocortin 2 decreases gorging on high-fat diet in both diet-induced obesity-prone and -resistant rats.

    Science.gov (United States)

    Cottone, P; Sabino, V; Nagy, T R; Coscina, D V; Levin, B E; Zorrilla, E P

    2013-12-01

    Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to have a role in obesity risk. The present study tested the hypothesis that (i) the microstructure of chronic high-fat diet intake differs between genetically selected diet-induced obesity (DIO) and diet-resistant (DR) rats, and (ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 μg). Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 μg, suppressing high-fat diet intake by ∼40% at the 3 μg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with two-third less water. Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically prone DIO rats, which otherwise show a 'gorging' meal pattern. These results open new opportunities of investigation toward treating some forms of DIO.

  3. Fish oil rich diet in comparison to saturated fat rich diet offered protection against lipopolysaccharide-induced inflammation and insulin resistance in mice.

    Science.gov (United States)

    Vijay-Kumar, Matam; Vanegas, Sally M; Patel, Nilam; Aitken, Jesse D; Ziegler, Thomas R; Ganji, Vijay

    2011-03-09

    Systemic chronic inflammation is linked to metabolic syndrome, type-2 diabetes, and heart disease. Lipopolysaccharide (LPS), a Gram negative microbial product, triggers inflammation through toll-like-receptor-4 (TLR-4) signaling. It has been reported that dietary fatty acids also modulate inflammation through TLR-4. We investigated whether fish oil (FO) rich diet in comparison to saturated fat (SF) rich diet would confer protection from pathologies induced by LPS. Twenty C57BL/6 mice were divided into two groups. One group received FO-diet and other received SF-diet ad libitum for 60 days. Diets were isocaloric containing 45% energy from fat. After 60-days of feeding, blood was collected after overnight fast. Mice were allowed to recover for 4-days, fasted for 5-hours, challenged with 100 ng/mL of LPS intraperitonially, and bled after 2-hours. After 7-days of recuperation, mice were challenged with 500 ng/mL of LPS intraperitonially and observed for physical health. Food intake was similar in FO- and SF-fed mice. FO-fed mice compared to SF-fed mice had significantly less body weight gain (P = 0.005), epididymal fat weight (P = 0.005), fasting blood glucose (70.8 vs 83.3 ng/dL; P effects of LPS in mice.

  4. High Levels of Avenanthramides in Oat-Based Diet Further Suppress High Fat Diet-Induced Atherosclerosis in Ldlr-/-Mice.

    Science.gov (United States)

    Thomas, Michael; Kim, Sharon; Guo, Weimin; Collins, F William; Wise, Mitchell L; Meydani, Mohsen

    2018-01-17

    Oats, in addition to cholesterol-lowering properties, contain unique antioxidants called avenanthramides (Avns), which inhibit both inflammatory cytokines and adhesion molecules in endothelial cells in culture. This study evaluated the effects of Avns of oats on atherosclerosis in Ldlr -/- mice, one of the most commonly used atherosclerosis mouse models with their similar cholesterol distributions to humans. The Ldlr -/- mice were fed a low fat, high fat, high fat containing regular oat brans with low levels of Avns (HFLA), or high fat containing regular oat brans with high levels of Avns (HFHA) diet. After 16 weeks of intervention, blood cholesterol and extent of aortic lesions were evaluated. We found that both oat-based diets reduced high fat diet-induced atheroma lesions in the aortic valve (p < 0.01). Furthermore, the effects of oat-based diets are more profound in HFHA mice than mice fed HFLA. Total plasma cholesterol levels were similarly reduced in both oat-supplemented mice. We concluded that oat bran diets reduce atheroma lesions and higher levels of Avns further reduce aortic lesions compared to regular oat bran. These preliminary in vivo data indicate that consumption of oats bran, with high Avns, has demonstrable beneficial effects on prevention of cardiovascular disease.

  5. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice.

    Science.gov (United States)

    Seimon, Radhika V; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A; Nguyen, Amy D; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F; Lau, Jackie; Herzog, Herbert; Sainsbury, Amanda

    2016-01-01

    Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)-(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, Pindex. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, Penergy-restricted groups. Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative to energy deficit in mice.

  6. Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss.

    Science.gov (United States)

    Nedeltcheva, Arlet V; Imperial, Jacqueline G; Penev, Plamen D

    2012-07-01

    Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-h blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean (s.d.) age 41 (5) years; BMI 27.4 (2.0) kg/m(2)) completed two 14-day treatments with hypocaloric diet and 8.5- or 5.5-h nighttime sleep opportunity in random order 7 (3) months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free fatty acids (FFA), 24-h blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 (0.3) BMI units) during each treatment. Bedtime restriction reduced sleep by 131 (30) min/day. Recurrent sleep curtailment decreased 24-h serum insulin concentrations (i.e., enhanced 24-h insulin economy) without changes in oral glucose tolerance and 24-h glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA, which suppressed normally following glucose ingestion, and lower total and low-density lipoprotein cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-h insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.

  7. Diet-induced obesity impairs mammary development and lactogenesis in murine mammary gland.

    Science.gov (United States)

    Flint, David J; Travers, Maureen T; Barber, Michael C; Binart, Nadine; Kelly, Paul A

    2005-06-01

    We have developed a mouse model of diet-induced obesity that shows numerous abnormalities relating to mammary gland function. Animals ate approximately 40% more calories when offered a high-fat diet and gained weight at three times the rate of controls. They exhibited reduced conception rates, increased peripartum pup mortality, and impaired lactogenesis. The impairment of lactogenesis involved lipid accumulation in the secretory epithelial cells indicative of an absence of copius milk secretion. Expression of mRNAs for beta-casein, whey acid protein, and alpha-lactalbumin were all decreased immediately postpartum but recovered as lactation was established over 2-3 days. Expression of acetyl-CoA carboxylase (ACC)-alpha mRNA was also decreased at parturition as was the total enzyme activity, although there was a compensatory increase in the proportion in the active state. By day 10 of lactation, the proportion of ACC in the active state was also decreased in obese animals, indicative of suppression of de novo fatty acid synthesis resulting from the supply of preformed fatty acids in the diet. Although obese animals consumed more calories in the nonpregnant and early pregnant states, they showed a marked depression in fat intake around day 9 of pregnancy before food intake recovered in later pregnancy. Food intake increased dramatically in both lean and obese animals during lactation although total calories consumed were identical in both groups. Thus, despite access to high-energy diets, the obese animals mobilized even more adipose tissue during lactation than their lean counterparts. Obese animals also exhibited marked abnormalities in alveolar development of the mammary gland, which may partially explain the delay in differentiation evident during lactogenesis.

  8. Case Study: Utilizing a Low FODMAP Diet to Combat Exercise-Induced Gastrointestinal Symptoms.

    Science.gov (United States)

    Lis, Dana; Ahuja, Kiran D K; Stellingwerff, Trent; Kitic, Cecilia M; Fell, James

    2016-10-01

    Athletes employ various dietary strategies in attempts to attenuate exercise-induced gastrointestinal (GI) symptoms to ensure optimal performance. This case-study outlines one of these GI-targeted approaches via the implementation of a short-term low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) diet, with the aim to attenuate persistent running specific GI symptoms in a recreationally competitive multisport athlete (male, 86 kg, 57.9 ml·kg·min(-1) V02max, 10-15 hr/week training, with no diagnosed GI disorder). Using a single-blinded approach a habitual diet was compared with a 6-day low FODMAP intervention diet (81 ± 5g vs 7.2 ± 5.7g FODMAP s/day) for their effect on GI symptoms and perceptual wellbeing. Training was similar during the habitual and dietary intervention periods. Postexercise (During) GI symptom ratings were recorded immediately following training. Daily GI symptoms and the Daily Analysis of Life Demands for Athletes (DALDA) were recorded at the end of each day. Daily and During GI symptom scores (scale 0-9) ranged from 0-4 during the habitual dietary period while during the low FODMAP dietary period all scores were 0 (no symptoms at all). DALDA scores for worse than normal ranged from 3-10 vs 0-8 in the habitual and low FODMAP dietary periods, respectively, indicating improvement. This intervention was effective for this GI symptom prone athlete; however, randomized-controlled trials are required to assess the suitability of low FODMAP diets for reducing GI distress in other symptomatic athletes.

  9. Protective Effects of Setarud (IMODTM on Development of Diet-Induced Hypercholesterolemia in Rabbits

    Directory of Open Access Journals (Sweden)

    MH Shahhosseiny

    2008-09-01

    Full Text Available Background: A new herbal drug setarud (IMODTM containing selenium, carotene, and flavonoids, was expected to have positive effects on lipid metabolism and liver functions, due to the nature of its primary components. This study was designed to determine effectiveness of the drug in reducing the risk of development of diet-induced hypercholesterolemia in laboratory animals. Methods: Two groups of male rabbits (n=10 per group as: intact and control groups on regular chow, were fed a high-cholesterol diet, and two experimental groups were maintained on the same diet and treated with different daily doses (0.02 g/kg and 0.04 g/kg of setarud (brand name IMOD®, Pars Roos, Iran. The treatment groups were then compared with the intact and control groups and with one another for the effects of the drug which was determined by changes in blood sugar, serum lipid levels, and liver function tests. Results: Results showed that drug had important benefits in alleviating the impact of high-cholesterol diet on serum lipids and liver function markers in drug-treated groups relative to hyperlipidemic controls (p < 0.001. A more favorable modification of total cholesterol and triglyceride levels and the atherogenic index was found in animals, which received 0.04 g/kg drug, as compared to the 0.02 g/kg dose group (p < 0.05. Assessment of serum total protein, albumin, transaminases, and bilirubin levels showed that no changes in liver function of control and drug-treated animals during the period of the study. Conclusion: From the results of this study it may concluded that setarud has dose-dependent positive effects on liver and lipid metabolism and may acts as an effective anti-hyperglycemic agent.

  10. Ghrelin did not change coronary angiogenesis in diet-induced obese mice.

    Science.gov (United States)

    Khazaei, M; Tahergorabi, Z

    2017-02-28

    Ghrelin is a 28 amino acids peptide that initially was recognized as an endogenous ligand for growth hormone secretagogue receptor (GHSR). Recently, a number of studies demonstrated that ghrelin is a cardiovascular hormone with a series cardiovascular effect. The main objective of this study was to investigate the effect of systemic ghrelin administration on angiogenesis in the heart and its correlation with serum leptin levels in normal and diet-induced obese mice. 24 male C57BL/6 mice 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 ND, respectively, for 14 weeks. Then, the ghrelin was injected subcutaneously 100µg/kg twice daily. After 10 days, the animals were sacrificed, blood samples were taken and the hearts were removed. The angiogenic response in the heart was assessed by immunohisochemical staining. HFD significantly increased angiogenesis in the heart expressed as the number of CD31 positive cells than standard diet. Ghrelin did not alter angiogenesis in the heart in both obese and control groups, however, it reduced serum nitric oxide (NO) and leptin levels in obese mice. There was a strong positive correlation between the number of CD31 positive cells and serum leptin concentration (r=0.74). Leptin as an angiogenic factor has a positive correlation with angiogenesis in the heart. Although systemic administration of ghrelin reduced serum leptin and NO levels in obese mice, however, it could not alter coronary angiogenesis.

  11. An extra virgin olive oil rich diet intervention ameliorates the nonalcoholic steatohepatitis induced by a high-fat "Western-type" diet in mice.

    Science.gov (United States)

    Jurado-Ruiz, Enrique; Varela, Lourdes M; Luque, Amparo; Berná, Genoveva; Cahuana, Gladys; Martinez-Force, Enrique; Gallego-Durán, Rocío; Soria, Bernat; de Roos, Baukje; Romero Gómez, Manuel; Martín, Franz

    2017-03-01

    We evaluated the protective effect of extra virgin olive oil (EVOO) in high-fat diets (HFDs) on the inflammatory response and liver damage in a nonalcoholic fatty liver disease (NAFLD) mouse model. C57BL/6J mice were fed a standard diet or a lard-based HFD (HFD-L) for 12 wk to develop NAFLD. HFD-fed mice were then divided into four groups and fed for 24 wk with the following: HFD-L, HFD-EVOO, HFD based on phenolics-rich EVOO, and reversion (standard diet). HFD-L-induced metabolic disorders were alleviated by replacement of lard with EVOO. EVOO diets improved plasma lipid profile and reduced body weight, plasma and epididymal fat INF-γ, IL-6 and leptin levels, and macrophage infiltration. Moreover, NAFLD activity scores were reduced. The liver lipid composition showed an increase in MUFAs, especially oleic acid, and a decrease in saturated fatty acids. Hepatic adiponutrin and Cd36 gene expression was upregulated in the EVOO groups. Liver ingenuity pathway analysis revealed in EVOO groups regulation of proteins involved in lipid metabolism, small molecule biochemistry, gastrointestinal disease, and liver regeneration. Dietary EVOO could repair HFD-induced hepatic damage, possibly via an anti-inflammatory effect in adipose tissue and modifications in the liver lipid composition and signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent.

    Science.gov (United States)

    Kim, Helen; Hall, Patti; Smith, Michelle; Kirk, Marion; Prasain, Jeevan K; Barnes, Stephen; Grubbs, Clinton

    2004-12-01

    Many popular dietary supplements are enriched in polyphenols such as the soy isoflavones, tea catechins, and resveratrol (from grape skins), each of which has been shown to have chemopreventive activity in cellular models of cancer. The proanthocyanidins, which are oligomers of the catechins, are enriched in grape seeds and form the basis of the dietary supplement grape seed extract (GSE). Evidence suggests that the proanthocyanidins may be metabolized to the monomeric catechins. This study was carried out to determine whether GSE added to rodent diets protected against carcinogen-induced mammary tumorigenesis in rats and whether this was affected by the composition of the whole diet. Female rats were begun on 5%, 1.25%, or 0% (control) GSE-supplemented diets at age 35 d. At age 50 d they were administered 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil at 80 mg/kg body weight. They were weighed and monitored weekly for tumor development until 120 d after DMBA administration. Administration of GSE in AIN-76A diet did not show any protective activity of GSE against DMBA-induced breast cancer. However, administration of GSE in a laboratory dry food diet (Teklad 4% rodent diet) resulted in a 50% reduction in tumor multiplicity. In similar experiments, genistein administered in AIN-76A diet also failed to show chemopreventive activity against the carcinogen N-methyl-N-nitrosourea; however, when administered at the same dose in the Teklad 4% rodent diet, genistein exhibited significant chemopreventive activity (44-61%). These results demonstrate that GSE is chemopreventive in an animal model of breast cancer; moreover, the diet dependency of the chemopreventive activity for both GSE and genistein suggests that whether or not a compound is chemopreventive may depend on the diet in which the agent is administered.

  13. Physical exercise antagonizes clinical and anatomical features characterizing Lieber-DeCarli diet-induced obesity and related metabolic disorders.

    Science.gov (United States)

    Gonçalves, Inês O; Passos, Emanuel; Rocha-Rodrigues, Sílvia; Torrella, Joan R; Rizo, David; Santos-Alves, Estela; Portincasa, Piero; Martins, Maria J; Ascensão, António; Magalhães, José

    2015-04-01

    Lieber-DeCarli diet has been used to induce obesity and non-alcoholic steatohepatitis (NASH). As scarce anatomical and clinical-related information on this diet model exists and being exercise an advised strategy to counteract metabolic diseases, we aimed to analyze the preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect of exercise on clinical/anatomical features of rats fed with Lieber-DeCarli diet. In the beginning of the protocol, Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 20), standard-diet VPA (SVPA, n = 10), high-fat diet sedentary (HS, n = 20) and high-fat diet VPA (HVPA, n = 10) groups. After 9-weeks, half (n = 10) of SS and HS groups were engaged in an ET program (8 wks/5 d/wk/60 min/day). At this time, a blood sample was collected for biochemical analysis. At the end of protocol (17-weeks) anatomic measures were assessed. Heart, liver, femur and visceral fat were weighted and blood was collected again. Liver section was used for histopathological examination. At 17-weeks, high-fat diet increased visceral adiposity (HS vs. SS), which was counteracted by both exercises. However, ET was the only intervention able to diminished obesity-related measures and the histological features of NASH. Moreover, blood analysis at 9 weeks showed that high-fat diet increased ALT, AST, cholesterol and HDL while VLDL and TG levels were decreased (HS vs. SS). Notably, although these parameters were counteracted after 9-weeks of VPA, they were transitory and not observed after 17-weeks. ET used as a therapeutic tool mitigated the clinical/anatomical-related features induced by Liber-DeCarli diet, thus possibly contributing to control obesity and metabolic disorders. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

    DEFF Research Database (Denmark)

    Tastesen, Hanne Sørup

    mice were fed obesity‐promoting diets with protein from different sources, in different forms and at different levels to evaluate the affect on development of obesity, glucose intolerance and dyslipidemia. Results: In the present study the dietary level of protein, 16 versus 32 percent energy from...... 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...... that the source and form of protein has great impact on development and prevention of diet‐induced adiposity, dyslipidemia, hyperinsulinemia and impairment of glucose tolerance through modulations of voluntary locomotor activity, energy expenditure and energy substrate metabolism in mice...

  15. Combining citrulline with atorvastatin preserves glucose homeostasis in a murine model of diet-induced obesity.

    Science.gov (United States)

    Capel, Frédéric; Chabrier, Gwladys; Pitois, Elodie; Rigaudière, Jean-Paul; Le Plenier, Servane; Durand, Christine; Jouve, Chrystèle; de Bandt, Jean-Pascal; Cynober, Luc; Moinard, Christophe; Morio, Béatrice

    2015-10-01

    NO is a crucial regulator of energy and lipid metabolism, whose homeostasis is compromised during obesity. Combination of citrulline and atorvastatin potentiated NO production in vitro. Here we have assessed the effects of this combination in mice with diet-induced obesity (DIO). C57BL/6J male mice were given a standard diet (control) or a high fat-high sucrose diet (DIO) for 8 weeks. DIO mice were then treated with DIO alone, DIO with citrulline, DIO with atorvastatin or DIO with citrulline and atorvastatin (DIOcit-stat) for 3 weeks. Thereafter, body composition, glucose tolerance, insulin sensitivity and liver fat metabolism were measured. DIOcit-stat mice showed lower body weight, fat mass and epididymal fat depots compared with other DIO groups. Unlike other DIO groups, glucose tolerance and insulin sensitivity of DIOcit-stat, along with blood glucose and insulin concentrations in response to feeding, were restored to control values. Refeeding-induced changes in liver lipogenic activity were also reduced in DIOcit-stat mice compared with those of DIO animals. This was associated with decreased gene expression of the transcription factor SREBP-1, liver X receptor α, ChREBP and of target lipogenic enzymes in the liver of DIOcit-stat mice compared with those of other DIO groups. The citrulline-atorvastatin combination prevented fat mass accumulation and maintained glucose homeostasis in DIO mice. Furthermore, it potentiated inhibition of hepatic de novo lipogenesis activity. This combination has potential for preservation of glucose homeostasis in patients receiving statin therapy. © 2015 The British Pharmacological Society.

  16. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

    Science.gov (United States)

    Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

    2014-11-01

    Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

  17. Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice.

    Science.gov (United States)

    Choi, Seoyoon; Choi, Youngshim; Choi, Yeji; Kim, Sohee; Jang, Jeehee; Park, Taesun

    2013-12-15

    This study examined the effect of piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13 weeks and elucidated potential underlying molecular mechanisms. Administration of piperine (50 mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice when they were administered piperine. However, piperine did not reduce body weight and other biochemical markers to an extent where they became equal to the levels found in the CD-fed mice. Piperine reversed HFD-induced down-regulation of adiponecitn-AMP-activated protein kinase (AMPK) signalling molecules which play an important role in mediating lipogenesis, fatty acid oxidation and insulin signalling in the livers of mice. The expressions of lipogenic target genes were decreased, whereas the expression of carnitine palmitoyltransferase 1 (CPT1) gene involved in fatty acid oxidation was increased in the livers of the Pin50 group. Piperine significantly decreased the phosphorylation of insulin receptor substrate-1 (IRS-1) compared with the HFD-fed mice. Administration of piperine appeared to reverse preexisting HFD-induced hepatic steatosis and insulin resistance, probably by activation of adiponectin-AMPK signalling in mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The antidepressant trans-2-phenylcyclopropylamine protects mice from high-fat-diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Adi Shemesh

    Full Text Available Mice treated with the antidepressant trans-2-phenylcyclopropylamine (2-PCPA were protected against diet-induced-obesity, and adiposity was reversed in pre-established diet-induced obese mice. Contrary to a recent report that inhibition of lysine-specific demethylase-1 by 2-PCPA results in increased energy expenditure, long-term 2-PCPA treatment had no such effect but its protection against obesity was associated with increased spontaneous locomotor activity, Moreover, pair feeding to assure equal caloric intake in wild type mice as well as in genetic hyperphagic mice (ob/ob also resulted in weight reduction in 2-PCPA treated mice that correlated with increased activity but no change in energy expenditure. Similarly, short-term intraperitoneal injections of 2-PCPA did not affect food intake but caused a substantial increase in locomotor activity in the light cycle that correlated with increased energy expenditure, whereas activity and energy expenditure were unchanged in the dark cycle. Lastly, 2-PCPA was also effective in reducing obesity in genetic UCP1 null mice. These data suggest that 2-PCPA can reduce obesity by decreasing food intake in the long term while increasing activity in the short-term. However, the protective and weight loss effects of 2-PCPA are independent of UCP1-regulated thermogenesis or basal energy expenditure.

  19. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats.

    Science.gov (United States)

    Ropelle, Eduardo R; Pauli, José R; Prada, Patrícia; Cintra, Dennys E; Rocha, Guilherme Z; Moraes, Juliana C; Frederico, Marisa J S; da Luz, Gabrielle; Pinho, Ricardo A; Carvalheira, José B C; Velloso, Licio A; Saad, Mario A; De Souza, Cláudio T

    2009-05-15

    Insulin signalling in the hypothalamus plays a role in maintaining body weight. The forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats. Thus, we investigated the effects of the intracerebroventricular (i.c.v.) microinfusion of Foxo1-antisense oligonucleotide (Foxo1-ASO) and evaluated the food consumption and weight gain in normal and diet-induced obese (DIO) rats. Three days of Foxo1-ASO microinfusion reduced the hypothalamic Foxo1 expression by about 85%. i.c.v. infusion of Foxo1-ASO reduced the cumulative food intake (21%), body weight change (28%), epididymal fat pad weight (22%) and fasting serum insulin levels (19%) and increased the insulin sensitivity (34%) in DIO but not in control animals. Collectively, these data showed that the Foxo1-ASO treatment blocked the orexigenic effects of Foxo1 and prevented the hyperphagic response in obese rats. Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity.

  20. Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Diet-Induced Metabolic Syndrome in Rats

    Directory of Open Access Journals (Sweden)

    Abishek Iyer

    2012-01-01

    Full Text Available The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido-cyclohexyloxy]-benzoic acid (t-AUCB, a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

  1. Temporal and Quantitative Analysis of Atherosclerotic Lesions in Diet-Induced Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Qi Yu

    2012-01-01

    Full Text Available The diet-induced atherosclerotic rabbit is an ideal model for atherosclerosis study, but temporal changes in atherosclerotic development in hypercholesterolemic rabbits are poorly understood. Japanese white rabbits were fed a high-cholesterol diet to induce sustained hypercholesterolemia, and each group of 10–12 animals was then sacrificed at 6, 12, 16, or 28 weeks. The rabbit aortas were harvested, and the sizes of the gross and intima atherosclerotic lesions were quantified. The cellular component of macrophages (Mφs and smooth muscle cells (SMCs in aortic intimal lesions was also quantified by immunohistochemical staining, and the correlation between plasma cholesterol levels and the progress of atherosclerotic lesions was studied. The ultrastructure of the atherosclerotic lesions was observed by transmission electron microscopy (TEM. Widely variable atherosclerotic plaques were found from 6 weeks to 28 weeks, and the lesional progress was closely correlated with cholesterol exposure. Interestingly, a relatively reduced accumulation of Mφ, an increased numbers of SMCs, and a damaged endothelial layer were presented in advanced lesions. Moreover, SMCs were closely correlated with cholesterol exposure and lesional progress for the whole period. Cholesterol exposure directly determines atherosclerotic progress in a rabbit model, and the changes in the cellular component of advanced lesions may affect plaque stability in an atherosclerotic rabbit model.

  2. Polyphenol Rich Extract of Garcinia pedunculata Fruit Attenuates the Hyperlipidemia induced by High Fat Diet

    Directory of Open Access Journals (Sweden)

    Rahul Sarma

    2016-08-01

    Full Text Available Fatty foods, the most common diet today are the crux of many metabolic disorders which need urgent attention. Garcinia pedunculata Roxb. (GP, Clusiaceae is a plant found available in Northeast (NE region of India, is considered to have versatile therapeutic properties. The people of this region has been using dried pulp of GP fruit for the treatment of different stomach related diseases traditionally. This study aimed at evaluating the potential therapeutic action of the polyphenol-rich methanolic extract (ME of the fruit in experimental induced obese rats. In vitro antioxidant and antidiabetic activity of GP extracts, i.e., fruit extract (GF and seed extract (GS were determined by using various methods viz., 1,1-diphenyl-2 picrylhydrazyl (DPPH, 2,2′-Azinobis (3-ethyl benzthiazoline-6-sulphonic acid (ABTS•+, nitroblue tetrazolium (NBT and α-glucosidase inhibition assay for detection of antihyperglycemic activity. In vivo antilipidemic and antiobesity activities were evaluated by administrating oral dose of GF for 60 days on a high-fat diet (HFD induced hyperlipidemia in the rat. GF showed higher antioxidant activity than GS by DPPH radical scavenging (IC50=4.01 µg/ml, ABTS•+ (IC50=0.82 µg/ml, NBT (IC50=0.07 µg/ml and also showed notable α-glucosidase inhibitory activity (IC50=19.26 µg/ml. Furthermore, GF treated rat revealed a reduction in the body weight (~60%, serum total cholesterol (33%, triglycerides (32%, low-density lipoprotein (38% and liver biomarker enzymes after 60 days HFD fed animals. Simultaneously, GF supplementation significantly protected the HFD induced changes in hematological parameters. Histological observations clearly differentiate the structural changes in liver of HFD and GF treated group. This novel dietary lipid adsorbing agent of GF exhibited prevention of hyperlipidemia induced by HFD in the rat.

  3. A high-fat diet induces obesity and impairs bone acquisition in young male mice.

    Science.gov (United States)

    Lu, Xiao-Mei; Zhao, Hong; Wang, En-Hua

    2013-04-01

    The postnatal development of obesity is highly associated with the excessive consumption of a high-calorie, high-fat diet (HFD). However, the correlation between HFD-induced pediatric obesity and skeletal development remains to be elucidated. In the present study, postnatal day 17 (PND17) mice were weaned on a HFD for eight weeks ad libitum to induce obesity. The HFD mice showed a significant increase in the total body weight and gonadal and abdominal fat mass compared with the control animals. Peripheral quantitative (pQ) CT scans of the tibial bone revealed that the bone mineral density (BMD), including the total, trabecular and cortical BMD, was unchanged between the HFD and control diet groups, but that it was inversely associated with body fat. By contrast, the bone mineral content (BMC) and trabecular area were significantly decreased in the HFD group compared with the control. RNA and protein were isolated from the femur. qPCR and western blot analyses showed a significant downregulation in the gene expression of the key canonical Wnt signaling molecule β-catenin, the osteoblastic cell differentiation marker Runt-related transcription factor 2 (Runx2) and also in the β-catenin gene encoded protein levels of the HFD mice when compared with the controls. Consistent with the increased fat mass in the HFD-induced obese animals, the expression of the adipogenic genes and aP2 was increased compared with the controls. Bone marrow cells were aspirated and the ex vivo bone marrow cell cultures showed that the number of colony-forming unit osteoblasts (CFU-OBs) per bone was significantly decreased in the samples from the HFD mice compared with those from the controls. These observations suggested that HFD-induced obesity in growing animals may affect the total available osteoblastic cell differentiation progenitors in the bone, while increasing adipogenesis. This may result in negative consequences for the bone later on in adult life.

  4. New Nordic Diet induced weight loss is accompanied by changes in metabolism and AMPK signalling in adipose tissue

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel; Lundsgaard, Annemarie; Jordy, Andreas Børsting

    2015-01-01

    consumed a New Nordic Diet (NND) or an Average Danish Diet (ADD) for 26 weeks in a controlled, free-living setting. SUBJECTS: 64 moderately obese women and men (44±2 years and BMI 31±1 kg·m(2)). INTERVENTION: Fasting blood samples and biopsies from the vastus lateralis muscle and subcutaneous abdominal...... muscle. NND induced greater reduction in fat mass than ADD (-6±1 kg and -2±1 kg, p

  5. Activation of Kupffer Cells Is Associated with a Specific Dysbiosis Induced by Fructose or High Fat Diet in Mice.

    Science.gov (United States)

    Ferrere, Gladys; Leroux, Anne; Wrzosek, Laura; Puchois, Virginie; Gaudin, Françoise; Ciocan, Dragos; Renoud, Marie-Laure; Naveau, Sylvie; Perlemuter, Gabriel; Cassard, Anne-Marie

    2016-01-01

    The increase consumption of fructose in diet is associated with liver inflammation. As a specific fructan substrate, fructose may modify the gut microbiota which is involved in obesity-induced liver disease. Here, we aimed to assess whether fructose-induced liver damage was associated with a specific dysbiosis, especially in mice fed a high fat diet (HFD). To this end, four groups of mice were fed with normal and HFD added or not with fructose. Body weight and glucose sensitivity, liver inflammation, dysbiosis and the phenotype of Kupffer cells were determined after 16 weeks of diet. Food intake was increased in the two groups of mice fed with the HFD. Mice fed with HFD and fructose showed a higher infiltration of lymphocytes into the liver and a lower inflammatory profile of Kupffer cells than mice fed with the HFD without fructose. The dysbiosis associated with diets showed that fructose specifically prevented the decrease of Mouse intestinal bacteria in HFD fed mice and increased Erysipelotrichi in mice fed with fructose, independently of the amount of fat. In conclusion, fructose, used as a sweetener, induced a dysbiosis which is different in presence of fat in the diet. Consequently, the activation of Kupffer cells involved in mice model of HFD-induced liver inflammation was not observed in an HFD/fructose combined diet. These data highlight that the complexity of diet composition could highly impact the development of liver lesions during obesity. Specific dysbiosis associated with the diet could explain that the progressions of liver damage are different.

  6. Activation of Kupffer Cells Is Associated with a Specific Dysbiosis Induced by Fructose or High Fat Diet in Mice.

    Directory of Open Access Journals (Sweden)

    Gladys Ferrere

    Full Text Available The increase consumption of fructose in diet is associated with liver inflammation. As a specific fructan substrate, fructose may modify the gut microbiota which is involved in obesity-induced liver disease. Here, we aimed to assess whether fructose-induced liver damage was associated with a specific dysbiosis, especially in mice fed a high fat diet (HFD. To this end, four groups of mice were fed with normal and HFD added or not with fructose. Body weight and glucose sensitivity, liver inflammation, dysbiosis and the phenotype of Kupffer cells were determined after 16 weeks of diet. Food intake was increased in the two groups of mice fed with the HFD. Mice fed with HFD and fructose showed a higher infiltration of lymphocytes into the liver and a lower inflammatory profile of Kupffer cells than mice fed with the HFD without fructose. The dysbiosis associated with diets showed that fructose specifically prevented the decrease of Mouse intestinal bacteria in HFD fed mice and increased Erysipelotrichi in mice fed with fructose, independently of the amount of fat. In conclusion, fructose, used as a sweetener, induced a dysbiosis which is different in presence of fat in the diet. Consequently, the activation of Kupffer cells involved in mice model of HFD-induced liver inflammation was not observed in an HFD/fructose combined diet. These data highlight that the complexity of diet composition could highly impact the development of liver lesions during obesity. Specific dysbiosis associated with the diet could explain that the progressions of liver damage are different.

  7. Niemann-Pick C2 protein expression regulates lithogenic diet-induced gallstone formation and dietary cholesterol metabolism in mice.

    Science.gov (United States)

    Balboa, Elisa; Morales, Gabriela; Aylwin, Paula; Carrasco, Gonzalo; Amigo, Ludwig; Castro, Juan; Rigotti, Attilio; Zanlungo, Silvana

    2012-01-01

    Niemann-Pick C2 protein (NPC2) is a lysosomal soluble protein that is highly expressed in the liver; it binds to cholesterol and is involved in intracellular cholesterol trafficking, allowing the exit of lysosomal cholesterol obtained via the lipoprotein endocytic pathway. Thus, this protein may play an important role in controlling hepatic cholesterol transport and metabolism. The aim of this work was to study the relevance of NPC2 protein expression in hepatic cholesterol metabolism, biliary lipid secretion and gallstone formation by comparing NPC2 hypomorph [NPC2 (h/h)] and wild-type mice fed control, 2% cholesterol, and lithogenic diets. NPC2 (h/h) mice exhibited resistance to a diet-induced increase in plasma cholesterol levels. When consuming the chow diet, we observed increased biliary cholesterol and phospholipid secretions in NPC2 (h/h) mice. When fed the 2% cholesterol diet, NPC2 (h/h) mice exhibited low and high gallbladder bile cholesterol and phospholipid concentrations, respectively. NPC2 (h/h) mice fed with the lithogenic diet showed reduced biliary cholesterol secretion, gallbladder bile cholesterol saturation, and cholesterol crystal and gallstone formation. This work indicates that hepatic NPC2 expression is an important factor in the regulation of diet-derived cholesterol metabolism and disposal as well as in diet-induced cholesterol gallstone formation in mice.

  8. 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

    2010-09-01

    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.

  9. The effects of diet- and diet plus exercise-induced weight loss on basal metabolic rate and acylated ghrelin in grade 1 obese subjects

    Directory of Open Access Journals (Sweden)

    Lopes AL

    2013-11-01

    Full Text Available André L Lopes,1 Ana Paula T Fayh,2,3 Luisa G de Souza Campos,4 Bruno C Teixeira,1 Randhall B Kreismann Carteri,1 Jerri L Ribeiro,4 Rogério Friedman,2 Álvaro Reischak-Oliveira1 1Exercise Research Laboratory, School of Physical Education, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; 2Endocrine Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; 3Health Sciences College of Trairi, Universidade Federal do Rio Grande do Norte, Santa Cruz, RN, Brazil; 4Centro Universitário Metodista – IPA, Porto Alegre, RS, Brazil Background: Diet and exercise are often prescribed as primary intervention regarding obesity-related disorders. Additionally, recent studies have shown beneficial effects of weight loss through diet and exercise in ghrelin concentrations in obese subjects. The aim of this study was to evaluate the effects of a 5% weight loss on lipid profile, resting metabolic rate (RMR, and acylated ghrelin (AG using two different methods of intervention (diet or diet plus exercise. Materials and methods: Eighteen subjects (twelve women and six men aged 20–40 years with a body mass index of 30–34.9 kg/m2 (grade 1 obesity were randomized into two intervention groups: diet (n=9 or diet plus exercise (n=9. Both groups underwent treatment until 5% of the initial body weight was lost. At baseline and upon completion, RMR and AG were analyzed. Results: Both groups showed a significant decrease in body fat percentage and fat mass. The diet-plus-exercise group showed a decrease in AG (pre: 54.4±25.3 pg/mL and post: 33.2±19.1 pg/mL and an increase in RMR (pre: 1,363±379 kcal/day, post: 1,633±223 kcal/day. Conclusion: These data suggest that diet plus exercise induced weight loss and had beneficial effects on AG concentration and RMR, essential factors to ensure the benefits of a weight-loss program. Keywords: exercise therapy, diet, energy regulation, obesity

  10. The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function.

    Science.gov (United States)

    Attenburrow, M J; Williams, C; Odontiadis, J; Powell, J; Van de Ouderaa, F; Williams, M; Cowen, P J

    2003-11-01

    Dieting in healthy women results in a decrease in the availability of tryptophan (TRP), the amino-acid precursor of serotonin (5-HT), for brain 5-HT synthesis. This is associated with increases in the prolactin response to 5-HT drug challenge suggesting a 'supersensitivity' of 5-HT neuroendocrine responses. The aim of the study was to assess whether increased TRP intake during dieting would prevent the changes in TRP availability and 5-HT neuroendocrine function. Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced TRP (1.8 g daily) or placebo in a double-blind, parallel group, design. TRP supplementation failed to modify the dieting-induced reduction in fasting TRP availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional TRP did not show enhanced prolactin responses to intravenous TRP challenge. The decrease in TRP availability produced by dieting may be due to increased TRP metabolism rather than decreased TRP intake. While TRP treatment did not increase fasting TRP availability it may have modified the effect of dieting on brain 5-HT function. Further studies will be needed to see if this effect of TRP has consequences for the effectiveness of dieting as means of weight control.

  11. Intrauterine Growth Retardation Increases the Susceptibility of Pigs to High-Fat Diet-Induced Mitochondrial Dysfunction in Skeletal Muscle

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    Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

    2012-01-01

    It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. PMID:22523560

  12. Antihyperlipidemic activity of Salacia chinensis root extracts in triton-induced and atherogenic diet-induced hyperlipidemic rats

    Science.gov (United States)

    Sikarwar, Mukesh S.; Patil, M. B.

    2012-01-01

    Objectives: The aim of this study has been to investigate the possible antihyperlipidemic effect of Salacia chinensis root extract in triton (400mg/kg b.w.)-induced and atherogenic diet-induced hyperlipidemic rats. Materials and Methods: Petroleum ether (60-80°C), chloroform, ethanol and aqueous extracts of Salacia chinensis roots were evaluated for antihyperlipidemic activity in triton- and atherogenic diet-induced hyperlipidemic rats. A comparison was also made between the action of Salacia chinensis root extract and a known antihyperlipidemic drug simvastatin (10 mg/kg body wt.). The results of the study were expressed as mean± S.E. and data was analyzed by using one way analysis of variance test (ANOVA) followed by Dunnett's t-test for multiple comparisons. Values with P < 0.05 were considered as significant. Results: Oral administration of 500 mg/kg body wt. of the chloroform extract and alcoholic extract of Salacia chinensis root exhibited a significant reduction (P<0.01) in serum lipid parameters like total cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipopreotein (VLDL) and increase in high density lipoprotein (HDL) in hyperlipidemic rats of both models as compared to hyperlipidemic control statistically. These extracts were found to possess better antihyperlipidemic potential as compared to pet ether and aqueous extract. Conclusions: Our results demonstrated that chloroform and alcoholic extract of Salacia chinensis roots possessed significant antihyperlipidemic activity and hence it could be a potential herbal medicine as adjuvant with existing therapy for the treatment of hyperlipidemia. PMID:22345877

  13. Unhealthy diet and ultrafine carbon black particles induce senescence and disease associated phenotypic changes.

    Science.gov (United States)

    Büchner, Nicole; Ale-Agha, Niloofar; Jakob, Sascha; Sydlik, Ulrich; Kunze, Kerstin; Unfried, Klaus; Altschmied, Joachim; Haendeler, Judith

    2013-01-01

    Telomerase activity in endothelial and lung epithelial cells. As a consequence, ufCB increased senescence of endothelial cells. To investigate whether ufCB show also effects in vivo, we instilled ufCB in concentrations not inducing inflammation into mice. Indeed, eNOS expression was reduced in the abdominal aorta of animals treated with ufCB. Thus, a combination of fructose and LDL in the diet and ufCB, as a major constituent of air pollution, seem to accelerate respiratory and cardiovascular cellular changes, which may compromise "healthy aging" and can lead to cardiovascular and pulmonary diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats

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    Whitsett Timothy

    2006-05-01

    Full Text Available Abstract Despite the advent of new and aggressive therapeutics, breast cancer remains a leading killer among women; hence there is a need for the prevention of this disease. Several naturally occurring polyphenols have received much attention for their health benefits, including anti-carcinogenic properties. Two of these are resveratrol, a component of red grapes, and epigallocatechin-3-gallate (EGCG, the major catechin found in green tea. In this study, we tested the hypothesis that these two polyphenols protect against chemically-induced mammary cancer by modulating mammary gland architecture, cell proliferation, and apoptosis. Female Sprague-Dawley CD rats were exposed to either resveratrol (1 g/kg AIN-76A diet, EGCG (0.065% in the drinking water, or control diet (AIN-76A for the entirety of their life starting at birth. At 50 days postpartum, rats were treated with 60 mg dimethylbenz[a]anthracene (DMBA/kg body weight to induce mammary cancer. Resveratrol, but not EGCG, suppressed mammary carcinogenesis (fewer tumors per rat and longer tumor latency. Analysis of mammary whole mounts from 50-day-old rats revealed that resveratrol, but not EGCG, treatment resulted in more differentiated lobular structures. Bromodeoxyuridine (BrdU incorporation studies showed that resveratrol treatment caused a significant reduction in proliferative cells in mammary terminal ductal structures at 50 days postpartum, making them less susceptible to carcinogen insult. The epithelial cells of terminal end buds in the mammary glands of resveratrol-treated rats also showed an increase in apoptotic cells compared to the control or EGCG-treated rats as measured by a DNA fragmentation assay. At the given doses, resveratrol treatment resulted in a serum resveratrol concentration of 2.00 μM, while treatment with EGCG resulted in a serum EGCG concentration of 31.06 nM. 17β-Estradiol, progesterone, and prolactin concentrations in the serum were not significantly affected

  15. META060 protects against diet-induced obesity and insulin resistance in a high-fat–diet fed mouse

    NARCIS (Netherlands)

    Vroegrijk, I.O.C.M.; Diepen, J.A. van; Berg, S.A. van den; Romijn, J.A.; Havekes, L.M.; Dijk, K.W. van; Darland, G.; Konda, V.; Tripp, M.L.; Bland, J.S.; Voshol, P.J.

    2012-01-01

    Objective: We investigated whether a reduced iso-α acid derived from an extract of Humulus lupulus L., META060, had an effect on weight gain, body composition, and metabolism in a high-fat–diet (HFD) fed mouse model. Methods: Weight gain was monitored for up to 20 wk in mice receiving a low-fat

  16. META060 protects against diet-induced obesity and insulin resistance in a high-fat-diet fed mouse

    NARCIS (Netherlands)

    Vroegrijk, I.O.; Diepen, J.A. van; Berg, S.A. van den; Romijn, J.A.; Havekes, L.M.; Dijk, K.W. van; Darland, G.; Konda, V.; Tripp, M.L.; Bland, J.S.; Voshol, P.J.

    2013-01-01

    OBJECTIVE: We investigated whether a reduced iso-alpha acid derived from an extract of Humulus lupulus L., META060, had an effect on weight gain, body composition, and metabolism in a high-fat-diet (HFD) fed mouse model. METHODS: Weight gain was monitored for up to 20 wk in mice receiving a low-fat

  17. Exercise protects against diet-induced insulin resistance through downregulation of protein kinase Cβ in mice.

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    Xiaoquan Rao

    Full Text Available Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase Cβ (PKCβ has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKCβ in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKCβ in exercise-attenuated insulin resistance in high-fat diet (HFD-fed mice. PKCβ(-/- and wild-type mice were fed a HFD with or without exercise training. PKC protein expression, body and tissue weight change, glucose and insulin tolerance, metabolic rate, mitochondria size and number, adipose inflammation, and AKT activation were determined to evaluate insulin sensitivity and metabolic changes after intervention. PKCβ expression decreased in both skeletal muscle and liver tissue after exercise. Exercise and PKCβ deficiency can alleviate HFD-induced insulin resistance, as evidenced by improved insulin tolerance. In addition, fat accumulation and mitochondrial dysfunction induced by HFD were also ameliorated by both exercise and PKCβ deficiency. On the other hand, exercise had little effect on PKCβ(-/- mice. Further, our data indicated improved activation of AKT, the downstream signal molecule of insulin, in skeletal muscle and liver of exercised mice, whereas PKCβ deficiency blunted the difference between sedentary and exercised mice. These results suggest that downregulation of PKCβ contributes to exercise-induced improvement of insulin resistance in HFD-fed mice.

  18. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  19. 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 (diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.

  20. 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.

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

    Science.gov (United States)

    de Lartigue, Guillaume; Barbier de la Serre, Claire; Espero, Elvis; Lee, Jennifer; Raybould, Helen E

    2012-01-01

    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. 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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Exercise ameliorates high fat diet induced cardiac dysfunction by increasing interleukin 10.

    Science.gov (United States)

    Kesherwani, Varun; Chavali, Vishalakshi; Hackfort, Bryan T; Tyagi, Suresh C; Mishra, Paras K

    2015-01-01

    Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming 1 h/day for 5 days/week for 8 weeks). The four treatment groups: normal diet (ND), HFD, HFD + exercise (HFD + Ex) and ND + Ex were analyzed for mean body weight, blood glucose level, TNF-α, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction by echocardiography. Mean body weights were increased in HFD but comparatively less in HFD + Ex. The level of TNF-α was elevated and IL-10 was downregulated in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was attenuated by exercise in the HFD + Ex group. The percentage ejection fraction and fractional shortening were decreased in HFD but comparatively increased in HFD + Ex. There was no difference between ND and ND + Ex for the above parameters except an increase in IL-10 level following exercise. Based on these results, we conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing obesity, inducing IL-10, and reducing TNF-α in mice.

  5. High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo.

    Science.gov (United States)

    Mantena, Sudheer K; Vaughn, Denty Paul; Andringa, Kelly K; Eccleston, Heather B; King, Adrienne L; Abrams, Gary A; Doeller, Jeannette E; Kraus, David W; Darley-Usmar, Victor M; Bailey, Shannon M

    2009-01-01

    NAFLD (non-alcoholic fatty liver disease), associated with obesity and the cardiometabolic syndrome, is an important medical problem affecting up to 20% of western populations. Evidence indicates that mitochondrial dysfunction plays a critical role in NAFLD initiation and progression to the more serious condition of NASH (non-alcoholic steatohepatitis). Herein we hypothesize that mitochondrial defects induced by exposure to a HFD (high fat diet) contribute to a hypoxic state in liver and this is associated with increased protein modification by RNS (reactive nitrogen species). To test this concept, C57BL/6 mice were pair-fed a control diet and HFD containing 35% and 71% total calories (1 cal approximately 4.184 J) from fat respectively, for 8 or 16 weeks and liver hypoxia, mitochondrial bioenergetics, NO (nitric oxide)-dependent control of respiration, and 3-NT (3-nitrotyrosine), a marker of protein modification by RNS, were examined. Feeding a HFD for 16 weeks induced NASH-like pathology accompanied by elevated triacylglycerols, increased CYP2E1 (cytochrome P450 2E1) and iNOS (inducible nitric oxide synthase) protein, and significantly enhanced hypoxia in the pericentral region of the liver. Mitochondria from the HFD group showed increased sensitivity to NO-dependent inhibition of respiration compared with controls. In addition, accumulation of 3-NT paralleled the hypoxia gradient in vivo and 3-NT levels were increased in mitochondrial proteins. Liver mitochondria from mice fed the HFD for 16 weeks exhibited depressed state 3 respiration, uncoupled respiration, cytochrome c oxidase activity, and mitochondrial membrane potential. These findings indicate that chronic exposure to a HFD negatively affects the bioenergetics of liver mitochondria and this probably contributes to hypoxic stress and deleterious NO-dependent modification of mitochondrial proteins.

  6. Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction by Increasing Interleukin 10

    Directory of Open Access Journals (Sweden)

    Varun eKesherwani

    2015-04-01

    Full Text Available Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α and attenuation of anti-inflammatory cytokine such as interleukin10 (IL-10 contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, eight week old, female C57BL/6J mice were fed with HFD and exercised (swimming 1hr/day for 5 days/week for eight weeks. The four treatment groups: normal diet (ND, HFD, HFD + exercise (HFD + Ex and ND + Ex were analyzed for mean body weight, blood glucose level, TNF-α, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction by echocardiography. Mean body weights were increased in HFD but comparatively less in HFD + Ex. The level of TNF-α was elevated and IL-10 was downregulated in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was attenuated by exercise in the HFD + Ex group. The percentage ejection fraction and fractional shortening were decreased in HFD but comparatively increased in HFD + Ex. There was no difference between ND and ND + Ex for the above parameters except an increase in IL-10 level following exercise. Based on these results, we conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing obesity, inducing IL-10, and reducing TNF-α in mice.

  7. Withania somnifera leaf alleviates cognitive dysfunction by enhancing hippocampal plasticity in high fat diet induced obesity model.

    Science.gov (United States)

    Manchanda, Shaffi; Kaur, Gurcharan

    2017-03-03

    Sedentary lifestyle, psychological stress and labor saving devices in this current society often disrupts the energy gain and expenditure balance leading to obesity. High caloric diet is associated with the high prevalence of cognitive dysfunction and neuropsychiatric disorders in addition to cardiovascular and metabolic abnormalities. The present study was aimed to elucidate the potential beneficial effect of dry leaf powder of Withania somnifera (Ashwagandha) in preventing the cognitive decline associated with diet induced obesity. Experiments were performed on four groups of young adult female rats: [Low fat diet (LFD) rats fed on regular low fat chow, High fat diet (HFD) rats on feed containing 30% fat by weight, Low fat diet extract (LFDE) rats given regular chow and dry leaf powder of Ashwagandha 1 mg/g of body weight (ASH) and high fat diet extract (HFDE) rats fed on diet containing high fat and dry leaf powder of ASH. All the rats were kept on their respective diet regimen for 12 weeks. ASH treated rats showed significant improvement in their working memory and locomotor coordination during behavioral studies as compared to HFD rats. At the molecular level, ASH treatment was observed to restore the levels of BDNF and its receptor TRKB as well as the expression of other synaptic regulators, which are highly implicated in synaptic plasticity. Further, ASH triggered the activation of PI3/AKT pathway of cell survival and plasticity by enhancing the levels of phosphorylated Akt-1 and immediate early genes viz. c-Jun and c-fos. ASH could be a key regulator in maintaining the synaptic plasticity in HFD induced obesity and can serve as a nootropic candidate against obesity induced cognitive impairments.

  8. Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose gene expression involved in adipogenesis and inflammation.

    Science.gov (United States)

    Choi, Eun Hye; Yang, Hyun Pil; Chun, Hyang Sook

    2012-03-01

    Chitooligosaccharide (CO) has been reported to have potential antiobestic effects in a few studies, but the antiobesity properties of CO and its related mechanisms in models of dietary obesity remain unclear. We investigated the effect of CO on body weight gain, size of adipocytes, adipokines, and lipid profiles in high-fat (HF) diet-induced obese mice and on the gene expression in adipose tissue using a complementary DNA microarray approach to test the hypothesis that CO supplementation would alleviate HF diet-induced obesity by the alteration of adipose tissue-specific gene expression. Male C57BL/6N mice were fed a normal diet (control), HF diet, or CO-supplemented HF diet (1% or 3%) for 5 months. Compared with the HF diet mice, mice fed the 3% CO-supplemented diet gained 15% less weight but did not display any change in food and energy intake. Chitooligosaccharide supplementation markedly improved serum and hepatic lipid profiles. Histologic examination showed that epididymal adipocyte size was smaller in mice fed the HF + 3% CO. Microarray analysis showed that dietary CO supplementation modulated adipogenesis-related genes such as matrix metallopeptidases 3, 12, 13, and 14; tissue inhibitor of metalloproteinase 1; and cathepsin k in the adipose tissues. Twenty-five percent of the CO-responsive genes identified are involved in immune responses including the inflammatory response and cytokine production. These results suggest that CO supplementation may help ameliorate HF diet-induced weight gain and improve serum and liver lipid profile abnormalities, which are associated, at least in part, with altered adipose tissue gene expression involved in adipogenesis and inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.

    Science.gov (United States)

    Liang, Lei; Shou, Xi-Ling; Zhao, Hai-Kang; Ren, Gu-Qun; Wang, Jian-Bang; Wang, Xi-Hui; Ai, Wen-Ting; Maris, Jackie R; Hueckstaedt, Lindsay K; Ma, Ai-Qun; Zhang, Yingmei

    2015-02-01

    Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial

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

    Directory of Open Access Journals (Sweden)

    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. Ingested capsaicinoids can prevent low-fat-high-carbohydrate diet and high-fat diet-induced obesity by regulating the NADPH oxidase and Nrf2 pathways.

    Science.gov (United States)

    Sahin, Kazim; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Ozdemir, Oguzhan; Juturu, Vijaya

    2017-01-01

    Capsaicinoids (CAPs), most commonly found in chili peppers, have a multitude of pharmacological and physiological effects, such as anti-inflammation, antioxidant, and anticancer effects. In the present study, we set out to investigate the hypothesis that CAPs mitigate obesity in rats and the possible mechanisms thereof. Rats were divided into six groups, including control (±10 mg CAPs/kg body weight [BW]), low-fat-high-sucrose diet (±10 mg CAPs/kg BW), and high-fat diet (±10 mg CAPs/kg BW). Blood samples and liver and aortic tissues were taken at the end of the study. CAPs supplementation significantly reduced hyperglycemia and hyperlipidemia (P<0.001) and ameliorated oxidative damage by reducing malondialdehyde concentrations in serum and liver and by increasing total antioxidant capacity in serum induced by the low-fat-high-sucrose and high-fat diets (P<0.001 for all). CAPs also depressed levels of NFκB p65, gp91phox, and p22phox, essential components of NADPH oxidase, in the aorta of rats. However, levels of Nrf2, Sirt1, and endothelial nitric oxide synthase were significantly increased in the aorta. CAPs may at least partially reduce adverse effects due to high-fat diet and sucrose consumption through regulation of energy metabolism, oxidative stress, and proteins involved in vasoprotection.

  12. Ingested capsaicinoids can prevent low-fat–high-carbohydrate diet and high-fat diet-induced obesity by regulating the NADPH oxidase and Nrf2 pathways

    Science.gov (United States)

    Sahin, Kazim; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Ozdemir, Oguzhan; Juturu, Vijaya

    2017-01-01

    Objective Capsaicinoids (CAPs), most commonly found in chili peppers, have a multitude of pharmacological and physiological effects, such as anti-inflammation, antioxidant, and anticancer effects. In the present study, we set out to investigate the hypothesis that CAPs mitigate obesity in rats and the possible mechanisms thereof. Materials and methods Rats were divided into six groups, including control (±10 mg CAPs/kg body weight [BW]), low-fat–high-sucrose diet (±10 mg CAPs/kg BW), and high-fat diet (±10 mg CAPs/kg BW). Blood samples and liver and aortic tissues were taken at the end of the study. Results CAPs supplementation significantly reduced hyperglycemia and hyperlipidemia (P<0.001) and ameliorated oxidative damage by reducing malondialdehyde concentrations in serum and liver and by increasing total antioxidant capacity in serum induced by the low-fat–high-sucrose and high-fat diets (P<0.001 for all). CAPs also depressed levels of NFκB p65, gp91phox, and p22phox, essential components of NADPH oxidase, in the aorta of rats. However, levels of Nrf2, Sirt1, and endothelial nitric oxide synthase were significantly increased in the aorta. Conclusion CAPs may at least partially reduce adverse effects due to high-fat diet and sucrose consumption through regulation of energy metabolism, oxidative stress, and proteins involved in vasoprotection. PMID:29180887

  13. Adiponectin deficiency rescues high-fat diet-induced hepatic injury, apoptosis and autophagy loss despite persistent steatosis.

    Science.gov (United States)

    Guo, R; Nair, S; Zhang, Y; Ren, J

    2017-09-01

    Background &aims:Low levels of