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Sample records for regulate fat accumulation

  1. Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation

    Science.gov (United States)

    Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

    2014-01-01

    Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFkβ pathway (IκBα) by TNF-α was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-α blockage by anti-TNF-α in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-α). PMID:25197426

  2. Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice.

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    Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

    2012-09-01

    Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

  3. Zanthoxylum piperitum DC ethanol extract suppresses fat accumulation in adipocytes and high fat diet-induced obese mice by regulating adipogenesis.

    Science.gov (United States)

    Gwon, So Young; Ahn, Ji Yun; Kim, Tae Wan; Ha, Tae Youl

    2012-01-01

    This study was conducted to determine the anti-obesity effects of Zanthoxylum piperitum DC fruit ethanol extract (ZPE) in 3T3-L1 adipocytes and obese mice fed a high-fat diet. We evaluated the influence of the addition of ZPE to a high-fat diet on body weight, adipose tissue weight, serum and hepatic lipids in C57BL/6 mice. In addition, adipogenic gene expression was determined by Western blot and real-time reverse transcription-PCR analysis. We assessed the effect of ZPE on 3T3-L1 preadipocyte differentiation. ZPE reduced weight gain, white adipose tissue mass, and serum triglyceride and cholesterol levels (pZPE decreased lipid accumulation and PPARγ, C/EBPα, SREBP-1, and FAS protein and mRNA levels in the liver. ZPE inhibited in vitro adipocyte differentiation in a dose-dependent manner and significantly attenuated adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP-1 in 3T3L1 cells. These findings suggest that Z. piperitum DC exerts an anti-obesity effect by inhibiting adipogenesis through the downregulation of genes involved in the adipogenesis pathway.

  4. How to get fat: nutritional mechanisms of seasonal fat accumulation in migratory songbirds

    Science.gov (United States)

    Bairlein, Franz

    2002-01-01

    Many migratory birds accumulate large amounts of lipids as the prime energy source for their long-distance flights. This fat accumulation is mostly under endogenous control, reflecting genetically programmed temporal shifts of the body mass set point. It is accompanied by an increase in daily food intake and food utilisation efficiency and by a seasonal shift in food selection. In particular, seasonal frugivory appears to play a key role in many migrants. Fruits have a high content of fatty acids indispensable for building up the specific depot lipids. In addition, plant secondary compounds seem to play some kind of supportive role, but the mechanisms are not yet known. The effect of being fat on the metabolic situation in migrant birds appears to be similar to the metabolic syndrome in obese humans. The fat migratory bird provides a model through which to study nutritional factors as well as the biochemical and endocrine regulation of food intake, body mass and obesity.

  5. Influence of muscle fiber type composition on early fat accumulation under high-fat diet challenge.

    Science.gov (United States)

    Hua, Ning; Takahashi, Hirokazu; Yee, Grace M; Kitajima, Yoichiro; Katagiri, Sayaka; Kojima, Motoyasu; Anzai, Keizo; Eguchi, Yuichiro; Hamilton, James A

    2017-01-01

    To investigate whether differences in muscle fiber types affect early-stage fat accumulation, under high fat diet challenge in mice. Twelve healthy male C57BL/6 mice experienced with short-term (6 weeks) diet treatment for the evaluation of early pattern changes in muscular fat. The mice were randomly divided into two groups: high fat diet (n = 8) and normal control diet (n = 4). Extra- and intra-myocellular lipid (EMCL and IMCL) in lumbar muscles (type I fiber predominant) and tibialis anterior (TA) muscle (type II fiber predominant) were determined using magnetic resonance spectroscopy (MRS). Correlation of EMCL, IMCL and their ratio between TA and lumbar muscles was evaluated. EMCL increased greatly in both muscle types after high fat diet. IMCL in TA and lumbar muscles increased to a much lower extent, with a slightly greater increase in TA muscles. EMCLs in the 2 muscles were positively correlated (r = 0.84, p = 0.01), but IMCLs showed a negative relationship (r = -0.84, p = 0.01). In lumbar muscles, high fat diet significantly decreased type I fiber while it increased type II fiber (all p≤0.001). In TA muscle, there was no significant fiber type shifting (p>0.05). Under short-time high fat diet challenge, lipid tends to initially accumulate extra-cellularly. In addition, compared to type II dominant muscle, Type I dominant muscle was less susceptible to IMCL accumulation but more to fiber type shifting. These phenomena might reflect compensative responses of skeletal muscle to dietary lipid overload in order to regulate metabolic homeostasis.

  6. Excessive visceral fat accumulation in advanced chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Furutate R

    2011-08-01

    Full Text Available Ryuko Furutate1, Takeo Ishii1,2, Ritsuko Wakabayashi1, Takashi Motegi1,2, Kouichi Yamada1,2, Akihiko Gemma2, Kozui Kida1,21Respiratory Care Clinic, Nippon Medical School, Kudan-Minami, Chiyoda-ku, Tokyo, Japan; 2Department of Internal Medicine, Division of Pulmonary Medicine, Infectious Diseases and Oncology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, JapanBackground: Previous studies have suggested links between chronic obstructive pulmonary disease (COPD, cardiovascular disease, and abdominal obesity. Although abdominal visceral fat is thought to be associated with cardiovascular risk factors, the degree of visceral fat accumulation in patients with COPD has not been directly studied. The aim of this study was to investigate the abdominal visceral fat accumulation and the association between visceral fat and the severity and changes in emphysema in COPD patients.Methods: We performed clinical and laboratory tests, including pulmonary function, dyspnea score, and the six-minute walking test in COPD patients (n = 101 and control, which included subjects with a smoking history but without airflow obstruction (n = 62. We used computed tomography to evaluate the abdominal visceral fat area (VFA, subcutaneous fat area (SFA, and the extent of emphysema.Results: The COPD group had a larger VFA than the control group. The prevalence of non-obese subjects with an increased VFA was greater in the Global Initiative for Chronic Obstructive Lung Disease Stages III and IV than in the other stages of COPD. The extent of emphysema was inversely correlated with waist circumference and SFA. However, VFA did not decrease with the severity of emphysema. VFA was positively correlated with the degree of dyspnea.Conclusion: COPD patients have excessive visceral fat, which is retained in patients with more advanced stages of COPD or severe emphysema despite the absence of obesity.Keywords: abdominal obesity, chronic obstructive pulmonary disease, emphysema

  7. Influence of dietary macronutrients on liver fat accumulation and metabolism

    Science.gov (United States)

    Parry, Siôn A; Hodson, Leanne

    2017-01-01

    The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated. PMID:28947639

  8. Influence of dietary macronutrients on liver fat accumulation and metabolism.

    Science.gov (United States)

    Parry, Siôn A; Hodson, Leanne

    2017-12-01

    The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Ectopic fat accumulation in patients with COPD: an ECLIPSE substudy

    Directory of Open Access Journals (Sweden)

    Martin M

    2017-01-01

    Full Text Available Mickaël Martin,1 Natalie Almeras,1 Jean-Pierre Després,1 Harvey O Coxson,2 George R Washko,3 Isabelle Vivodtzev,4 Emiel FM Wouters,5 Erica Rutten,6 Michelle C Williams,7 John T Murchison,8 William MacNee,7 Don D Sin,2 François Maltais1 On behalf of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE Study Group 1Research Centre, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC, 2Department of Radiology, University of British Columbia, Vancouver, BC, Canada; 3Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 4Hypoxia Pathophysiology Laboratory, Grenoble University Hospital, Grenoble, France; 5Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, 6Research and Development, CIRO, Horn, the Netherlands; 7Department of Respiratory Medicine, University of Edinburgh, 8Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK Background: Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities.Methods: Computed tomography (CT images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2–L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration and CSA of MT. A dose–response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced

  10. Influence of dietary macronutrients on liver fat accumulation and metabolism

    OpenAIRE

    Parry, Siôn A; Hodson, Leanne

    2017-01-01

    The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the av...

  11. Correlation between visceral fat accumulation, leptin and eating disorder in peritoneal dialysis patients

    International Nuclear Information System (INIS)

    Mochizuki, Takahiro; Kojima, Chiari; Oishi, Tetsuya; Takahashi, Motohiro

    2003-01-01

    Eating disorder may be a major factor for protein-energy malnutrition occurs in patients with chronic renal failure (CRF). Some peritoneal dialysis (PD) patients demonstrate eating disorder in association with massive visceral fat accumulation. Markedly elevated leptin levels have been documented in CRF patients, especially in those who are treated with PD. Leptin is secreted by adipocytes, regulates both body composition and appetite behavior. This study evaluated the correlation between visceral fat accumulation, leptin and eating disorder in PD patients. Plasma leptin, albumin, insulin-like growth factor-1 (IGF-1), normalized protein catabolic rate (nPCR), C-reactive protein (CRP) and body composition were measured in 46 PD patients (27 males and 19 females; median age 62.7 years). Computed tomography was used for determination of visceral fat area (VFA) and subcutaneous fat area (SFA), at the initial state and during PD. The VFA and the SFA increased during PD treatment, and the ratio of increase in each fat area was significantly higher in VFA than in SFA (1.47±0.63 vs. 1.23±0.41 p<0.01, respectively). Serum leptin elevated (19.5±21.9 ng/mL), and correlated significantly with the percentage of body fat (r=0.584), body mass index (BMI: r=0.574), VFA (r=0.476) and SFA (r=0.684). Dietary intake correlated inversely with the visceral fat mass, and the low nPCR group had a higher VFA/BMI ratio (p<0.05). A negative correlation was found between nPCR and either serum leptin (r=-0.52), leptin/BMI (r=-0.44), or CRP (r=-0.55). Our data suggest that visceral fat accumulation and hyperleptinemia in PD patients are closely associated with eating disorder. Therefore, a new peritoneal solution containing an alternative osmotic agent instead of glucose may be useful to prevent accumulation of visceral fat in PD patients. (author)

  12. Intermittent cold exposure enhances fat accumulation in mice.

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    Hyung Sun Yoo

    Full Text Available Due to its high energy consuming characteristics, brown adipose tissue (BAT has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE, unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis.

  13. HORMONAL REGULATION OF SELENIUM ACCUMULATION BY PLANTS

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    N. A. Golubkina

    2015-01-01

    Full Text Available Hormonal regulation is considered to be a unique mechanism controlling growth and development of living organism. The review discusses the correlations between pant hormonal status of non-accumulators and hyper-accumulators of Se with the accumulation levels of this microelement. The phenomenon of stimulation and redistribution of selenium as a result of phytohormone treatment, the peculiarities of phytohormones effect among different species and cultivars, and influence of plant sexualization on selenium accumulation are described in article. Data of hormonal regulation of selenium level for spinach, garlic, perennial onion, Brassica chinenesis and Valeriana officialis are presented in the review.

  14. Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat Accumulation in High-Fat Diet-Fed Mice.

    Science.gov (United States)

    Tamura, Shohei; Honda, Kazuhisa; Morinaga, Ryoji; Saneyasu, Takaoki; Kamisoyama, Hiroshi

    2017-01-01

    The combination of diet and exercise is the first choice for the treatment of obesity and metabolic syndrome. We previously reported that enzymatically synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats. However, the effect of the combination of ESG and exercise on abdominal fat accumulation has not yet been investigated. Our goal in this study was therefore to evaluate the effects of dietary ESG and its combination with exercise on abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25 m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG and exercise significantly reduced the weights of abdominal adipose tissues. In addition, the combination of ESG and exercise significantly suppressed abdominal fat accumulation, suggesting that ESG and exercise showed an additive effect. Exercise significantly increased the mRNA levels of lipid metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor delta; factor-delta (PPARδ), carnitin palmitoyltransferase b, adipose triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle. On the other hand, dietary ESG significantly decreased the mRNA levels of PPARδ and ATGL in the gastrocnemius muscle. These results suggest that the combined treatment of ESG and exercise effectively suppresses abdominal fat accumulation in HFD-fed mice by different mechanisms.

  15. Body fat accumulation in zebrafish is induced by a diet rich in fat and reduced by supplementation with green tea extract.

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    Shinichi Meguro

    Full Text Available Fat-rich diets not only induce obesity in humans but also make animals obese. Therefore, animals that accumulate body fat in response to a high-fat diet (especially rodents are commonly used in obesity research. The effect of dietary fat on body fat accumulation is not fully understood in zebrafish, an excellent model of vertebrate lipid metabolism. Here, we explored the effects of dietary fat and green tea extract, which has anti-obesity properties, on body fat accumulation in zebrafish. Adult zebrafish were allocated to four diet groups and over 6 weeks were fed a high-fat diet containing basal diet plus two types of fat or a low-fat diet containing basal diet plus carbohydrate or protein. Another group of adult zebrafish was fed a high-fat diet with or without 5% green tea extract supplementation. Zebrafish fed the high-fat diets had nearly twice the body fat (visceral, subcutaneous, and total fat volume and body fat volume ratio (body fat volume/body weight of those fed low-fat diets. There were no differences in body fat accumulation between the two high-fat groups, nor were there any differences between the two low-fat groups. Adding green tea extract to the high-fat diet significantly suppressed body weight, body fat volume, and body fat volume ratio compared with the same diet lacking green tea extract. 3-Hydroxyacyl-coenzyme A dehydrogenase and citrate synthase activity in the liver and skeletal muscle were significantly higher in fish fed the diet supplemented with green tea extract than in those fed the unsupplemented diet. Our results suggest that a diet rich in fat, instead of protein or carbohydrate, induced body fat accumulation in zebrafish with mechanisms that might be similar to those in mammals. Consequently, zebrafish might serve as a good animal model for research into obesity induced by high-fat diets.

  16. Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.

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    Escande, Carlos; Nin, Veronica; Pirtskhalava, Tamar; Chini, Claudia C S; Tchkonia, Tamar; Kirkland, James L; Chini, Eduardo N

    2015-01-01

    Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus and that it is only when the maximum fat accumulation capacity is reached and fatty acid spillover occurs into to peripheral tissues that metabolic diseases develop. In this regard, identifying the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid spillover is imperative. Here we identify the deleted in breast cancer 1 (DBC1) protein as a key regulator of fat storage capacity of adipocytes. We found that knockout (KO) of DBC1 facilitated fat cell differentiation and lipid accumulation and increased fat storage capacity of adipocytes in vitro and in vivo. This effect resulted in a "healthy obesity" phenotype. DBC1 KO mice fed a high-fat diet, although obese, remained insulin sensitive, had lower free fatty acid in plasma, were protected against atherosclerosis and liver steatosis, and lived longer. We propose that DBC1 is part of the molecular machinery that regulates fat storage capacity in adipocytes and participates in the "turn-off" switch that limits adipocyte fat accumulation and leads to fat spillover into peripheral tissues, leading to the deleterious effects of caloric surplus. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Screening for bioactive metabolites in plant extracts modulating glucose uptake and fat accumulation

    DEFF Research Database (Denmark)

    El-Houri, Rime Bahij; Kotowska, Dorota Ewa; C. B. Olsen, Louise

    2014-01-01

    while weekly activating PPARγ without promoting adipocyte differentiation. In addition, these extracts were able to decrease fat accumulation in C. elegans. Methanol extracts of summer savory (Satureja hortensis), common elder, and broccoli (Brassica oleracea) enhanced glucose uptake in myotubes...

  18. Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is significantly correlated with liver fat accumulation in patients with type 2 diabetes mellitus.

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    Kurinami, Noboru; Sugiyama, Seigo; Morita, Ayami; Yoshida, Akira; Hieshima, Kunio; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouch, Katsunori; Jinnouchi, Tomio; Jinnouchi, Hideaki

    2018-05-01

    Obesity and ectopic fat accumulation are important conditions of type 2 diabetes mellitus (T2DM). Our aim was to determine whether bioelectrical impedance body composition analysis combined with blood test results could estimate liver ectopic fat accumulation in patients with treatment-naïve T2DM. Subjects were 119 untreated T2DM patients. Computed tomography scans were performed to calculate the liver to spleen attenuation ratio (L/S ratio) as a measure of liver fat accumulation, with excess liver fat accumulation defined as an L/S ratio analysis using InBody770. The Nagelkerke R 2 test showed that the muscle mass/fat mass ratio (muscle/fat ratio) was the most suitable variable among anthropometric factors and body component indexes for estimating liver fat accumulation. The muscle/fat ratio was significantly correlated with the L/S ratio (ρ = 0.4386, P analysis showed that the muscle/fat ratio (odds ratio 0.40, 95% confidence interval 0.22-0.73, P ratio 1.06, 95% confidence interval 1.02-1.10, P analysis, the cutoff value of the muscle/fat ratio for excess liver fat accumulation was 2.34. In patients with treatment-naïve T2DM, the muscle/fat ratio and ALT are useful for estimating the presence of excess liver fat accumulation in daily clinical practice. Copyright © 2018. Published by Elsevier B.V.

  19. Effect of a weight cycle on visceral fat accumulation

    NARCIS (Netherlands)

    van der Kooy, K; Leenen, R; Seidell, J C; Deurenberg, P.; Hautvast, J.G.A.J.

    1993-01-01

    Magnetic resonance imaging was used to study the effect of a single weight cycle on three fat depots: the visceral and subcutaneous abdominal depots and the subcutaneous depot at the trochanter level. Obese subjects (17 men, 15 women) were examined before and after weight-loss intervention and 67 wk

  20. Fat metabolism during exercise: mechanisms of regulation

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    Monique da Silva Gevaerd

    2006-12-01

    Full Text Available Fats are important energetic fuel to exercise. However, the regulation of fat uptake during exercise is unclear. The main objective of this review was to focus on physiological control mechanisms of mobilization, transport and fat uptake during exercise. The articles of fat metabolism were searched in Pubmed and Lilacs indexes. Classical and current papers were preferred. Evidence suggests that transport of fatty acids (FA from extracellular to intracellular spaces could be the main factor to limit fatty acid uptake. Future studies on fat uptake during exercise can focus on this mechanism. In intense exercise, the lower blood fl ow in the adipose tissue and higher fatty acid reesterifi cation rate impairs fat uptake during exercise. Supplementation of the FA has been used, however, the ideal quantities and forms to prevent gastrointestinal discomfort were not yet determined. In the biological point of view, intramuscular reserve of FA could be more effi cient, because is not necessary to FA to cross the cell membrane. RESUMO Os lipídios são considerados importantes fontes energéticas para a realização de exercícios físicos. Entretanto, os mecanismos de regulação do consumo desse substrato durante o exercício não estão totalmente esclarecidos. O objetivo principal da presente revisão foi abordar mecanismos fisiológicos de controle da mobilização, transporte e utilização de gordura durante o exercício. Os trabalhos indexados no banco de dados Pubmed e Lilacs sobre metabolismo de gordura, foram analisados e os clássicos e recentes foram preferencialmente utilizados. A partir dos dados recentes da literatura, especula-se que o transporte de ácidos graxos do meio extracelular para o meio intracelular pode constituir um dos principais mecanismos limitantes no consumo desse substrato. Estudos sobre o consumo de lipídios durante o exercício devem ser focados sobre esse mecanismo. Em exercício intenso, o menor fl uxo de sangue

  1. Kefir prevented excess fat accumulation in diet-induced obese mice.

    Science.gov (United States)

    Choi, Jae-Woo; Kang, Hye Won; Lim, Won-Chul; Kim, Mi-Kyoung; Lee, In-Young; Cho, Hong-Yon

    2017-05-01

    Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein-cholesterol concentrations. Overall, kefir has the potential to prevent obesity.

  2. Effects of puerarin on lipid accumulation and metabolism in high-fat diet-fed mice.

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    Guodong Zheng

    Full Text Available In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD, and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK, carnitine acyltransferase (CAT and hormone-sensitive lipase (HSL were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2 was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases.

  3. Trans fats in New Zealand: time for labelling regulations?

    Science.gov (United States)

    Gladding, Patrick; Benatar, Jocelyne R

    2007-11-09

    Trans fats (trans fatty acids) are commonly used for deep frying in restaurants and in the fast food, snack food, fried food, and baked goods industries, often to extend the shelf life of foods. However they are widely considered to be harmful to health. Trans fats were banned in New York City restaurants from 1 July 2007, and there is growing vocal opposition to trans fats in the European Union. Denmark became the first country, in March 2003, to introduce laws regulating the content of trans fats in food (maximum of 2% of edible fats and oils). What are trans fats, what harm do they cause, and should New Zealand also consider imposing mandatory regulations on their use in food? This article explores the issues.

  4. Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice

    DEFF Research Database (Denmark)

    Brandt, Claus; Hansen, Rasmus Hvass; Hansen, Jakob Bondo

    2015-01-01

    -fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were......OBJECTIVE: Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling....../glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24h fasting. CONCLUSION: Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content....

  5. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Soyoung Park

    2016-01-01

    Full Text Available Korean pine nut oil (PNO has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO (PC, SC or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD, for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively compared with SHFD. Hepatic triacylglycerol (TG level was significantly lower in PHFD than the SHFD (26% lower. PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response.

  6. The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism.

    Science.gov (United States)

    Matsuzawa, Yuji; Funahashi, Tohru; Nakamura, Tadashi

    2011-01-01

    Although abdominal obesity or visceral obesity is considered to be one of the components of metabolic syndrome and to have an important role in a cluster of cardiovascular risks, there is no consensus about the definition and diagnostic criteria for this syndrome, probably because there is considerable disagreement about the location and definition of abdominal obesity or visceral obesity.In this review article, the important role of visceral fat accumulation in the development of a variety of lifestyle-related diseases is shown, including cardiovascular disease based on our clinical studies using CT scans, and the mechanism of these disorders is discussed, focusing on adipocytokines, especially adiponectin.The importance of diagnosing metabolic syndrome, in which visceral fat accumulation plays an essential role in the development of multiple risk factors, should be emphasized because lifestyle modification for the reduction of visceral fat may be very effective for the reduction of risks of this type, namely metabolic syndrome in the narrow sense.

  7. Fenugreek Seed Extract Inhibit Fat Accumulation and Ameliorates Dyslipidemia in High Fat Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Parveen Kumar

    2014-01-01

    Full Text Available This study investigated the inhibitory effect of aqueous extract of Trigonella foenum-graecum seeds (AqE-TFG on fat accumulation and dyslipidemia in high fat diet- (HFD- induced obese rats. Female Wistar rats were fed with HFD ad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days + AqE-TFG (0.5 and 1.0 g/kg or orlistat (10 mg/kg from day 8 to 28, respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI, white adipose tissue (WAT weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST, alanine amino transferase (ALT, and lactate dehydrogenase (LDH levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS and elevated the antioxidant enzyme (glutathione (GSH, superoxide dismutase (SOD, and catalase (CAT levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS and glucose-6-phosphate dehydrogenase (G6PD activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes.

  8. An infection of human adenovirus 31 affects the differentiation of preadipocytes into fat cells, its metabolic profile and fat accumulation.

    Science.gov (United States)

    Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Sawicki, Grzegorz; Woźniak, Mieczysław

    2016-03-01

    The primary issue undertaken in this study was to test the hypothesis that preadipocytes would have intrinsically elevated propensity to differentiate into mature adipocytes due to HAdV31 infection. To prove that, the metabolic and molecular mechanisms responsible for HAdV31-induced adipogenesis were examined. 3T3L1 cells (mouse embryonic fibroblast, adipose like cell line) were used as a surrogate model to analyze an increased proliferation, differentiation, and maturation of preadipocytes infected with human adenovirus. An expression of E4orf1, C/EBP-β, PPAR-γ, GAPDH, aP2, LEP, and fatty acid synthase genes, intracellular lipid accumulation as well as cytokine release from the fat cells were assessed. Data showed that HAdV31 increased an expression of C/EBP-β and PPAR-γ genes leading to an enhanced differentiation of preadipocytes into fat cells. Besides, overexpression of GAPDH and fatty acid synthase, and decreased expression of leptin caused an increased accumulation of intracellular lipids. Secretion of TNF-α and IL-6 from HAdV31-infected cells was strongly decreased, leading to unlimited virus replication. The results obtained from this study provided the evidences that HAdV31, likewise previously documented HAdV36, is a subsequent human adenovirus affecting the differentiation and lipid accumulation of 3T3L1 cells. © 2015 Wiley Periodicals, Inc.

  9. Clinical Studies of Sweet Bee Venom to The Effect of Abdominal Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Lim, Chung-San

    2008-06-01

    Full Text Available Objective The purpose of this study was to investigate the effects of Sweet Bee Venom to the abdominal fat accumulation clinically. Methods The 20 healthy women volunteers who showed the notice of this study by the home page of Sangji University were treated with Sweet Bee Venom(SBV during twenty times. To investigate the effects of Sweet Bee Venom of the abdominal fat accumulation, abdominal CT, LFT, Thermography, BMI, Inbody 3.0 etc. were performed during clinical trials. And statistical analysis was carried out the data of 10 volunteers who performed all the schedule of this study. Results Following results were obtained from the clinical studies Sweet Bee Venom showed the effect of decreased the body weight, thickness of abdominal skin and fat layer, BMI, and increased abdominal heat, but they are not showed statistical significant. Conclusions These results suggest that treatment Sweet Bee Venom on the abdomen was effective to decrease fat tissue but for the treatment of obesity was performed with right diet program and exercise.

  10. Hormonal control of fat accumulation in L-glutamate-treated obese rats

    International Nuclear Information System (INIS)

    Remke, H.; Wilsdorf, A.; Mueller, F.

    1988-01-01

    Persistently decreased concentrations of the growth hormone and the tissue-nonepinephrine in connection with growth retardation and obesity were investigated concerning the effects on cells of epididymal adipose tissue in postnatally injured glutamate-treated rats using 14 C-labelled tracers. Diminished secretion of growth hormone causes in adipocytes increased glucose intake, amplification of the insulin effect, and fat accumulation. A supersensitivity towards norepinephrine in adipocytes in vitro is due to diminished concentration of this hormone in the tissue. Insulin resistance is developed at the beginning of the stationary phase of obesity in these animals. (author)

  11. Small heterodimer partner (SHP deficiency protects myocardia from lipid accumulation in high fat diet-fed mice.

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    Full Text Available The small heterodimer partner (SHP regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR γ expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO mice compared to those of wild-type (WT mice (nominal p value < 0.05. Consistent with these gene expression changes, the left ventricular masses of SHP KO mice were significantly higher than WT mice (76.8 ± 20.5 mg vs. 52.8 ± 6.8 mg, P = 0.0093. After 12 weeks of high fat diet (HFD, SHP KO mice gained less weight and exhibited less elevation in serum-free fatty acid and less ectopic lipid accumulation in the myocardium than WT mice. According to microarray analysis, genes regulated by PPARγ1 and PPARα were down-regulated in myocardia of SHP KO mice compared to their expression in WT mice after HFD, suggesting that the reduction in lipid accumulation in the myocardium resulted from a decrease in lipogenesis regulated by PPARγ. We confirmed the reduced expression of PPARγ1 and PPARα target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD.

  12. Tissue Specific Expression Of Sprouty1 In Mice Protects Against High Fat Diet Induced Fat Accumulation, Bone Loss, And Metabolic Dysfunction

    Science.gov (United States)

    Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J.; Liaw, Lucy

    2012-01-01

    We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss. PMID:22142492

  13. Undesirable compounds in oils and fats: analysis and regulation

    Directory of Open Access Journals (Sweden)

    Lacoste Florence

    2003-03-01

    Full Text Available The aim of this paper is to present, for some undesirable compounds representative of the major origins, a comparison between the efficiency of the analytical methods used (sensitivity, precision and existing regulations. An idea of the different origins of the presence of undesirable compounds in oils and fats is given. Then a focus is done on guidelines on contaminant analysis provided by European directives or Codex Alimentarius. The reliability of some existing test methods compared to regulations is also examined: lead, hexane, polycyclic aromatic hydrocarbons, and pesticide residues.

  14. MiR-27a suppresses triglyceride accumulation and affects gene mRNA expression associated with fat metabolism in dairy goat mammary gland epithelial cells.

    Science.gov (United States)

    Lin, Xian-Zi; Luo, Jun; Zhang, Li-Ping; Wang, Wei; Shi, Heng-Bo; Zhu, Jiang-Jiang

    2013-05-25

    MicroRNAs (miRNAs), a well-defined group of small RNAs containing about 22 nucleotides, participate in various biological metabolic processes. miR-27a is a miRNA that is known to regulate fat synthesis and differentiation in preadipocyte cells. However, little is known regarding the role that miR-27a plays in regulating goat milk fat synthesis. In this study, we determined the miR-27a expression profile in goat mammary gland and found that miR-27a expression was correlated with the lactation cycle. Additionally, prolactin promoted miR-27a expression in goat mammary gland epithelial cells. Further functional analysis showed that over-expression of miR-27a down-regulated triglyceride accumulation and decreased the ratio of unsaturated/saturated fatty acid in mammary gland epithelial cells. miR-27a also significantly affected mRNA expression related to milk fat metabolism. Specifically, over-expression of miR-27a reduced gene mRNA expression associated with triglyceride synthesis by suppressing PPARγ protein levels. This study provides the first experimental evidence that miR-27a regulates triglyceride synthesis in goat mammary gland epithelial cells and improves our understanding about the importance of miRNAs in milk fat synthesis. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  15. Intra-abdominal fat accumulation is a hypertension risk factor in young adulthood: A cross-sectional study.

    Science.gov (United States)

    Takeoka, Atsushi; Tayama, Jun; Yamasaki, Hironori; Kobayashi, Masakazu; Ogawa, Sayaka; Saigo, Tatsuo; Kawano, Hiroaki; Abiru, Norio; Hayashida, Masaki; Maeda, Takahiro; Shirabe, Susumu

    2016-11-01

    Accumulation of intra-abdominal fat is related to hypertension. Despite this, a relationship between hypertension and intra-abdominal fat in young adulthood is not clear. In this study, we verify whether intra-abdominal fat accumulation increases a hypertension risk in young adult subjects.In a cross-sectional study, intra-abdominal fat area was measured using a dual bioelectrical impedance analysis instrument in 697 university students (20.3 ± 0.7 years, 425 men). Blood pressure and anthropometric factors were measured. Lifestyle variables including smoking, drinking, physical activity, and eating behavior were assessed with questionnaire. High blood pressure risk (systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg) with increasing intra-abdominal fat area was evaluated.Participants were divided into 5 groups according to their intra-abdominal fat area (≤24.9, 25-49.9, 50-74.9, 75-99.9, and ≥100 cm). As compared with the values of the smallest intra-abdominal fat area group, the crude and lifestyle-adjusted odds ratios (ORs) were elevated in larger intra-abdominal fat area groups [OR 1.31, 95% confidence interval (CI) 0.66-2.80; OR 3.38, 95% CI 1.60-7.57; OR 7.71, 95% CI 2.75-22.22; OR 18.74, 95% CI 3.93-105.64, respectively). The risk increase was observed only in men.Intra-abdominal fat accumulation is related to high blood pressure in men around 20 years of age. These results indicate the importance of evaluation and reduction of intra-abdominal fat to prevent hypertension.

  16. Fat-specific protein 27 regulates storage of triacylglycerol

    DEFF Research Database (Denmark)

    Keller, P.; Petrie, J.T.; Rose, P. De

    2008-01-01

    FSP27 (fat-specific protein 27) is a member of the cell death-inducing DNA fragmentation factor-alpha-like effector (CIDE) family. Although Cidea and Cideb were initially characterized as activators of apoptosis, recent studies have demonstrated important metabolic roles for these proteins...... in several cell types without induction of adipocyte genes. Increased triacylglycerol is likely due to decreased beta-oxidation of nonesterified fatty acids. Altered flux of fatty acids into triacylglycerol may be a direct effect of FSP27 function, which is localized to lipid droplets in 293T cells and 3T3-L...... decreases with total fat mass but is not associated with measures of insulin resistance (e.g. homeostasis model assessment). Together, these data indicate that FSP27 binds to lipid droplets and regulates their enlargement Udgivelsesdato: 2008/5/23...

  17. Milk fat globules: fatty acid composition, size and in vivo regulation of fat liquidity.

    Science.gov (United States)

    Timmen, H; Patton, S

    1988-07-01

    Populations of large and small milk fat globules were isolated and analyzed to determine differences in fatty acid composition. Globule samples were obtained by centrifugation from milks of a herd and of individual animals produced under both pasture and barn feeding. Triacylglycerols of total globule lipids were prepared by thin layer chromatography and analyzed for fatty acid composition by gas chromatography. Using content of the acids in large globules as 100%, small globules contained fewer short-chain acids, -5.9%, less stearic acid, -22.7%, and more oleic acids, +4.6%, mean values for five trials. These differences are consistent with alternative use of short-chain acids or oleic acid converted from stearic acid to maintain liquidity at body temperature of milk fat globules and their precursors, intracellular lipid droplets. Stearyl-CoA desaturase (EC 1.14.99.5), which maintains fluidity of cellular endoplasmic reticulum membrane, is suggested to play a key role in regulating globule fat liquidity. Possible origins of differences between individual globules in fatty acid composition of their triacylglycerols are discussed.

  18. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice

    Directory of Open Access Journals (Sweden)

    Do Hyeong Gwon

    2017-09-01

    Full Text Available Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI. Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs from ω6-Polyunsaturated fatty acids (ω6-PUFAs without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt were divided into four groups: wt sham (n = 10, fat-1 sham (n = 10, wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15, and fat-1 IRI (n = 15. Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR. Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

  19. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

    Science.gov (United States)

    Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

    2017-09-30

    Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

  20. Regulation of PCP by the Fat signaling pathway

    Science.gov (United States)

    Matis, Maja; Axelrod, Jeffrey D.

    2013-01-01

    Planar cell polarity (PCP) in epithelia, orthogonal to the apical–basal axis, is essential for numerous developmental events and physiological functions. Drosophila model systems have been at the forefront of studies revealing insights into mechanisms regulating PCP and have revealed distinct signaling modules. One of these, involving the atypical cadherins Fat and Dachsous and the ectokinase Four-jointed, appears to link the direction of cell polarization to the tissue axes. We discuss models for the function of this signaling module as well as several unanswered questions that may guide future investigations. PMID:24142873

  1. Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction.

    Science.gov (United States)

    Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J; Liaw, Lucy

    2012-09-28

    We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

  2. Relationship between Protein Accumulation Regulation and Yield Formation in Soybean

    Institute of Scientific and Technical Information of China (English)

    CHEN Lihua; LI Jie; LIU Lijun; ZU Wei

    2006-01-01

    Three different genotypes soybeans were adopted in this experiment under three fertilizer levels.The object of this study was to investigate protein accumulation regulation of soybean cultivars under the condition of different nutrient levels, and their effects on soybean yield and quality, and to provide theoretical evidence for breed, cultivation and agricultural production, also man-powered controllable locations. The concentration of N in the leaves declined after seedling stage, then increased again at stage of early flowering, and started to decrease up to leaf senescence, declined rapidly from seed-filling season to stage of yellow ripeness. The concentration of N in the stems and pod walls declined with growth stage. High seed protein genotypes exhibited higher N assimilating and partitioning during whole growth stages. Pod walls were media of N partitioning. Protein was accumulated mainly during the later period of reproductive growth stage up to harvest, so plant growth after stage of yellow ripeness could not be neglected.

  3. Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans.

    Science.gov (United States)

    Chang, Hong-Chou; Peng, Chiung-Huei; Yeh, Da-Ming; Kao, Erl-Shyh; Wang, Chau-Jong

    2014-04-01

    Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.

  4. A 12-Week Aerobic Exercise Program Reduces Hepatic Fat Accumulation and Insulin Resistance in Obese, Hispanic Adolescents

    NARCIS (Netherlands)

    van der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili D.; Sauer, Pieter J. J.; Haymond, Morey W.; Rodriguez, Luisa M.; Sunehag, Agneta L.

    2010-01-01

    The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized

  5. Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

    Science.gov (United States)

    Katsumura, Masanori; Takagi, Shoko; Oya, Hana; Tamura, Shohei; Saneyasu, Takaoki; Honda, Kazuhisa; Kamisoyama, Hiroshi

    2017-08-01

    Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet. © 2016 Japanese Society of Animal Science.

  6. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    International Nuclear Information System (INIS)

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In; Park, Sang-Joon; Lee, Sang Gyu; Lee, Inkyu; Kim, Myoung Ok; Yoon, Duhak; Ryoo, Zae Young

    2014-01-01

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes

  7. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Sang Gyu [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Inkyu [School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842 (Korea, Republic of); Kim, Myoung Ok [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Yoon, Duhak, E-mail: dhyoon@knu.ac.kr [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Ryoo, Zae Young, E-mail: jaewoong64@hanmail.net [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of)

    2014-02-14

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.

  8. A fat-derived metabolite regulates a peptidergic feeding circuit in Drosophila.

    Directory of Open Access Journals (Sweden)

    Do-Hyoung Kim

    2017-03-01

    Full Text Available Here, we show that the enzymatic cofactor tetrahydrobiopterin (BH4 inhibits feeding in Drosophila. BH4 biosynthesis requires the sequential action of the conserved enzymes Punch, Purple, and Sepiapterin Reductase (Sptr. Although we observe increased feeding upon loss of Punch and Purple in the adult fat body, loss of Sptr must occur in the brain. We found Sptr expression is required in four adult neurons that express neuropeptide F (NPF, the fly homologue of the vertebrate appetite regulator neuropeptide Y (NPY. As expected, feeding flies BH4 rescues the loss of Punch and Purple in the fat body and the loss of Sptr in NPF neurons. Mechanistically, we found BH4 deficiency reduces NPF staining, likely by promoting its release, while excess BH4 increases NPF accumulation without altering its expression. We thus show that, because of its physically distributed biosynthesis, BH4 acts as a fat-derived signal that induces satiety by inhibiting the activity of the NPF neurons.

  9. [Effect of jiaotai pill on pancreatic fat accumulation and islet cell apoptosis in rats with type 2 diabetes].

    Science.gov (United States)

    Zou, Xin; Liu, De-Liang; Lu, Fu-Er; Dong, Hui; Xu, Li-Jun; Luo, Yun-Huan; Wang, Kai-Fu

    2014-06-01

    In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.

  10. Substantial replacement of lactose with fat in a high-lactose milk replacer diet increases liver fat accumulation but does not affect insulin sensitivity in veal calves.

    Science.gov (United States)

    Pantophlet, A J; Gerrits, W J J; Vonk, R J; van den Borne, J J G C

    2016-12-01

    In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown. Therefore, an experiment was designed to compare the effects of a high-lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal calves. Sixteen male Holstein-Friesian calves (120±2.8kg of BW) were assigned to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks. After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps, respectively. Postprandial blood samples were collected to assess glucose, insulin, and triglyceride responses to feeding, and 24-h urine was collected to quantify urinary glucose excretion. At the end of the trial, liver and muscle biopsies were taken to assess triglyceride contents in these tissues. Long-term exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity (averaging 4.2±0.5×10 -2 [(mg/kg∙min)/(μU/mL)]) and insulin secretion. Responses to feeding were greater for plasma glucose and tended to be greater for plasma insulin in HL calves than in HF calves. Urinary glucose excretion was substantially higher in HL calves (75±13g/d) than in HF calves (21±6g/d). Muscle triglyceride content was not affected by treatment and averaged 4.5±0.6g/kg, but liver triglyceride content was higher in HF calves (16.4±0.9g/kg) than in HL calves (11.2±0.7g/kg), indicating increased hepatic fat accumulation. We conclude that

  11. Effects of garcinia cambogia (Hydroxycitric Acid on visceral fat accumulation: a double-blind, randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Kohsuke Hayamizu, MS

    2003-09-01

    Full Text Available Background: (--Hydroxycitric acid (HCA is an active ingredient extracted from the rind of the Indian fruit Garcinia cambogia. It inhibits adenosine triphosphate citrate lyase and has been used in the treatment of obesity. Objective: The primary end point of this study was the effects of 12 weeks of G cambogia extract administration on visceral fat accumulation. The secondary end points were body indices (including height, body weight, body mass index [BMI], waist and hip circumference, and waist–hip ratio and laboratory values (including total cholesterol, triacylglycerol, and free fatty acid. Methods: This study was performed according to a double-blind, randomized, placebo-controlled, parallel-group design. Subjects aged 20 to 65 years with a visceral fat area >90 cm2 were enrolled. Subjects were randomly assigned to receive treatment for 12 weeks with G cambogia (containing 1000 mg of HCA per day or placebo. At the end of the treatment period, both groups were administered placebo for 4 weeks to assess any rebound effect. Each subject underwent a computed tomography scan at the umbilical level at −2, 0, 12, and 16 weeks. Results: Forty-four subjects were randomized at baseline, and 39 completed the study (G cambogia group, n=18; placebo group, n=21. At 16 weeks, the G cambogia group had significantly reduced visceral, subcutaneous, and total fat areas compared with the placebo group (all indices P<0.001. No severe adverse effect was observed at any time in the test period. There were no significant differences in BMI or body weight at week 12, but there were slight numeric decreases in body weight and BMI in men. There were no signs of a rebound effect from week 12 to week 16. Conclusion: G cambogia reduced abdominal fat accumulation in subjects, regardless of sex, who had the visceral fat accumulation type of obesity. No rebound effect was observed. It is therefore expected that G cambogia may be useful for the prevention and reduction

  12. The obesity-induced transcriptional regulator TRIP-Br2 mediates visceral fat endoplasmic reticulum stress-induced inflammation.

    Science.gov (United States)

    Qiang, Guifen; Kong, Hyerim Whang; Fang, Difeng; McCann, Maximilian; Yang, Xiuying; Du, Guanhua; Blüher, Matthias; Zhu, Jinfang; Liew, Chong Wee

    2016-04-25

    The intimate link between location of fat accumulation and metabolic disease risk and depot-specific differences is well established, but how these differences between depots are regulated at the molecular level remains largely unclear. Here we show that TRIP-Br2 mediates endoplasmic reticulum (ER) stress-induced inflammatory responses in visceral fat. Using in vitro, ex vivo and in vivo approaches, we demonstrate that obesity-induced circulating factors upregulate TRIP-Br2 specifically in visceral fat via the ER stress pathway. We find that ablation of TRIP-Br2 ameliorates both chemical and physiological ER stress-induced inflammatory and acute phase response in adipocytes, leading to lower circulating levels of inflammatory cytokines. Using promoter assays, as well as molecular and pharmacological experiments, we show that the transcription factor GATA3 is responsible for the ER stress-induced TRIP-Br2 expression in visceral fat. Taken together, our study identifies molecular regulators of inflammatory response in visceral fat that-given that these pathways are conserved in humans-might serve as potential therapeutic targets in obesity.

  13. Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity

    DEFF Research Database (Denmark)

    Ratner, Cecilia; Madsen, Andreas Nygaard; Kristensen, Line Vildbrad

    2015-01-01

    In order to characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model, where the rats were fed a Western diet for 76 days. Body composition was assessed by MRI scans and as expected the OP rats developed a higher...... likewise had higher RER values indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive...... to ghrelin's orexigenic effects as well as ghrelin-induced attenuation of activity and energy expenditure. Thus, increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, while ghrelin...

  14. Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms

    DEFF Research Database (Denmark)

    Srinivasan, Supriya; Sadegh, Leila; Elle, Ida C

    2008-01-01

    We investigated serotonin signaling in C. elegans as a paradigm for neural regulation of energy balance and found that serotonergic regulation of fat is molecularly distinct from feeding regulation. Serotonergic feeding regulation is mediated by receptors whose functions are not required for fat...... feeding behavior. These findings suggest that, as in mammals, C. elegans feeding behavior is regulated by extrinsic and intrinsic cues. Moreover, obesity and thinness are not solely determined by feeding behavior. Rather, feeding behavior and fat metabolism are coordinated but independent responses...

  15. Accumulation of dietary fish fatty acids in the body fat reserves of some carnivorous fur-bearing animals

    Directory of Open Access Journals (Sweden)

    Kirsti Rouvinen

    1992-09-01

    Full Text Available Body fat composition of the mink (Mustela vison, polecat (Mustela putorius, and the raccoon dog (Nyctereutes procyonoides was studied. The animals were fed a wet diet, supplemented with 5 % lard (LA or fish oil (FO for 5-6 months. At pelting, five animals per dietary group were sampled. Dietary levels of cetoleic (C22:1ω11, eicosapentaenoic (EPA, C20:5ω3, and docosahexaenoic (DHA, C22:6ω3 acids were 0.4, 0.3, and 0.5% in the fat of the LA diet, and 7.6, 4.2 and 4.3% in the FO diet, respectively. In the FO diet, EPA and DHA accumulated especially in the liver and heart, while cetoleic acid showed the highest affinity to the heart muscle and subcutaneous fat. The highest levels of EPA were found in raccoon dogs and polecats fed the FO diet. The mean EPA levels ranged from 6.7-9.3% in the liver fat and 7.2-8.0% in the heart muscle fat. In the mink, the corresponding values were 2.7% and 3.9%, respectively. DHA levels were the highest in the liver fat of the polecats, being 18.5% in the FO diet. In addition, the liver in raccoon dogs fed the FO diet (13.8% differed significantly from themink (9.4%. The differences in the accumulation of these long-chained marine fatty acids were apparently caused by species differences in the efficiency of their peroxisomal β-oxidation.

  16. Familial Accumulation of Social Anxiety Symptoms and Maladaptive Emotion Regulation.

    Science.gov (United States)

    Asbrand, Julia; Svaldi, Jennifer; Krämer, Martina; Breuninger, Christoph; Tuschen-Caffier, Brunna

    2016-01-01

    Social anxiety is thought to be strongly related to maladaptive emotion regulation (ER). As social anxiety symptoms accumulate in families, we hypothesize that maladaptive ER is also more prevalent in families with anxious children. Thus, we analyze differences in emotion regulation of both child and mother in relation to social anxiety, as well as both their ER strategies in dealing with anxiety. Further, a positive relation between child and maternal ER strategies is assumed. Children (aged 9 to 13 years) with social, anxiety disorder (SAD; n = 25) and healthy controls (HC, n = 26) as well as their mothers completed several measures of social anxiety and trait ER strategies towards anxiety. As ER of children is still in development, age is considered as covariate. SAD children and their mothers reported more maladaptive ER strategies than HC dyads. Maternal maladaptive ER was related negatively to child adaptive ER which was further moderated by the child's age. Maladaptive ER strategies seem to contribute to the exacerbation of social anxiety in both mother and child. Mothers reporting maladaptive ER may have difficulties supporting their child in coping with social anxiety while simultaneously also experiencing heightened levels of anxiety. Deeper understanding of interactional processes between mothers and children during development can assist the comprehension of factors maintaining SAD. Implications for future research and possible consequences for interventions are discussed.

  17. Familial Accumulation of Social Anxiety Symptoms and Maladaptive Emotion Regulation.

    Directory of Open Access Journals (Sweden)

    Julia Asbrand

    Full Text Available Social anxiety is thought to be strongly related to maladaptive emotion regulation (ER. As social anxiety symptoms accumulate in families, we hypothesize that maladaptive ER is also more prevalent in families with anxious children. Thus, we analyze differences in emotion regulation of both child and mother in relation to social anxiety, as well as both their ER strategies in dealing with anxiety. Further, a positive relation between child and maternal ER strategies is assumed.Children (aged 9 to 13 years with social, anxiety disorder (SAD; n = 25 and healthy controls (HC, n = 26 as well as their mothers completed several measures of social anxiety and trait ER strategies towards anxiety. As ER of children is still in development, age is considered as covariate.SAD children and their mothers reported more maladaptive ER strategies than HC dyads. Maternal maladaptive ER was related negatively to child adaptive ER which was further moderated by the child's age.Maladaptive ER strategies seem to contribute to the exacerbation of social anxiety in both mother and child. Mothers reporting maladaptive ER may have difficulties supporting their child in coping with social anxiety while simultaneously also experiencing heightened levels of anxiety. Deeper understanding of interactional processes between mothers and children during development can assist the comprehension of factors maintaining SAD. Implications for future research and possible consequences for interventions are discussed.

  18. Dopamine Signaling Regulates Fat Content through β-Oxidation in Caenorhabditis elegans

    Science.gov (United States)

    Barros, Alexandre Guimarães de Almeida; Bridi, Jessika Cristina; de Souza, Bruno Rezende; de Castro Júnior, Célio; de Lima Torres, Karen Cecília; Malard, Leandro; Jorio, Ado; de Miranda, Débora Marques; Ashrafi, Kaveh; Romano-Silva, Marco Aurélio

    2014-01-01

    The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots. PMID:24465759

  19. Fatness

    DEFF Research Database (Denmark)

    Hansen, Anne Katrine Kleberg

    In 1727, the English physician Thomas Short wrote: “I believe no Age did ever afford more instances of Corpulency than our own.” Even in the 18th century, fatness was addressed as an issue of special contemporary concern. This thesis probes concepts and perceptions of fatness in Western European...... Medicine c. 1700–1900. It has been written with particular attention to whether and how fatness has been regarded as a disease during that period in history. One purpose of the thesis is to investigate the immediate period before fatness allegedly became problematized. Another purpose has been to grasp...

  20. Ginger Essential Oil Ameliorates Hepatic Injury and Lipid Accumulation in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Lai, Yi-Syuan; Lee, Wan-Ching; Lin, Yu-En; Ho, Chi-Tang; Lu, Kuan-Hung; Lin, Shih-Hang; Panyod, Suraphan; Chu, Yung-Lin; Sheen, Lee-Yan

    2016-03-16

    The objective of this study was to investigate the hepatoprotective efficacy and mechanism of action of ginger essential oil (GEO) against the development of nonalcoholic fatty liver disease (NAFLD). Mice were maintained on either a control diet or high-fat diet (HFD) supplemented with GEO (12.5, 62.5, and 125 mg/kg) or citral (2.5 and 25 mg/kg) for 12 weeks. We demonstrated that GEO and its major component (citral) lowered HFD-induced obesity in a dose-dependent manner, accompanied by anti-hyperlipidemic effects by reducing serum free fatty acid, triglyceride, and total cholesterol levels. Moreover, liver histological results showed that administration of 62.5 and 125 mg/kg GEO and 25 mg/kg citral significantly reduced hepatic lipid accumulation. Further assessment by Western blotting and investigation of the lipid metabolism revealed that hepatic protein expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and cytochrome P450 2E1 (CYP2E1) were down-regulated by GEO and citral, indicating that GEO and citral suppressed HFD-stimulated lipid biosynthesis and oxidative stress. Furthermore, GEO and citral effectively enhanced the antioxidant capacities and reduced inflammatory response in mouse liver, which exerted protective effects against steatohepatitis. Collectively, GEO and citral exhibited potent hepatoprotective effects against NAFLD induced by HFD in obese mice. Thus, GEO might be an effective dietary supplement to ameliorate NAFLD-related metabolic diseases, and citral could play a vital role in its management.

  1. Regulation of glycogenolysis in the locust fat body during flight

    NARCIS (Netherlands)

    Marrewijk, W.J.A. van; Broek, A.Th.M. van den; Beenakkers, A.M.Th.

    1980-01-01

    Glycogen reserves in the fat body of Locusta migratoria decrease dramatically during the first two hours of flight. In fat body of rested locusts only 10% of glycogen phosphorylase occurs in the active form. The enzyme is activated significantly during flight, when up to one-third of the total

  2. Visceral fat accumulation is associated with colorectal cancer in postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Jee-Yon Lee

    Full Text Available BACKGROUND: Obesity is a known risk factor for colorectal cancer (CRC, and emerging data suggest that this association is mediated by visceral fat rather than total body fat. However, there is a lack of studies evaluating the association between visceral fat area and the prevalence of CRC. METHODS: To investigate the relationship between visceral adiposity and prevalence of CRC, data of 497 women diagnosed with CRC and 318 apparently healthy women were analysed and data of well-balanced 191 pairs of women with CRC and healthy women matched based on propensity scores were additionally analysed. Diagnosis of CRC was confirmed by colonoscopy and histology. Metabolic parameters were assessed, along with body composition, using computed tomography. RESULTS: The median visceral fat area was significantly higher in the CRC group compared with the control group before and after matching. The prevalence of CRC increased significantly with increasing visceral fat tertiles after matching (p for trend <0.01. A multivariate analysis showed that mean visceral fat area of individuals in the 67th percentile or greater group was associated with an increased prevalence of CRC (adjusted odds ratio: 1.80; 95% confidence interval: 1.12-2.91 before matching and adjusted odds ratio: 2.96; 95% confidence interval: 1.38-6.33 compared with that of individuals in the 33th percentile or lower group. CONCLUSION: Thus, we conclude that visceral fat area is positively associated with the prevalence of CRC. Although we could not determine the causality, visceral adiposity may be associated with the risk of CRC. Further prospective studies are required to determine the benefits of controlling visceral obesity for reducing CRC risk.

  3. Dietary constituents reduce lipid accumulation in murine C3H10 T1/2 adipocytes: A novel fluorescent method to quantify fat droplets

    Directory of Open Access Journals (Sweden)

    Fuhrer Erna

    2011-05-01

    Full Text Available Abstract Background Adipocyte volume (fat accumulation and cell number (adipogenesis is increased in obese individuals. Our objective was the identification of dietary constituents with inhibitory effects on triglyceride formation during adipogenesis. Therefore an in vitro adipose cell assay in murine C3H10 T1/2 cells was developed, which enabled rapid quantification of intracellular fat droplet accumulation during adipocyte differentiation. Results were corroborated by expression levels of several specific adipogenic and lipogenic genes which are known to regulate triglyceride accumulation. Methods C3H10 T1/2 adipocyte differentiation was conducted with rosiglitazone in the presence of test compounds for 7 days. Accumulation of intracellular lipid droplets was measured using the Cellomics® ArrayScan® VTI HCS reader and SpotDetector® BioApplication from ThermoFisher. Fluorescent images were automatically acquired and analysed employing the fluorescent dyes BODIPY® 493/503 and Hoechst 33342, for staining neutral lipids and localisation of nuclei, respectively. The expression levels of adipogenic and lipogenic genes, such as PPARα and PPARγ, C/EBPα, aP2, adiponectin, LPL and HSL, CPT-1β, ACC1, Glut4 and FAS, were determined by quantitative RT-PCR. Dietary ingredients including PUFAs, carotenoids, polyphenols and catechins were tested for their effect on lipid accumulation. Results The ω-3 PUFAs docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, the carotenoid β-carotene and hydroxytyrosol exhibited the strongest inhibitory effects on the rosiglitazone-stimulated lipid formation. (all-E-lycopene and epigallocatechin gallate (EGCG showed a moderate inhibition, whereas resveratrol did not reduce fat droplet formation. Additionally, it was demonstrated that adipogenic and lipogenic gene expression was attenuated. DHA, β-carotene and hydroxytyrosol inhibited the gene expression of PPARγ, C/EBPα, aP2 and CPT-1β. Conclusion This in

  4. Skeletal Muscle and Liver Lipidomics and the Regulation of FAT/CD36

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting

    induced obesity in mice, we observed an increased muscle and liver lipid content, analyzed by mass spectrometry, concomitant with decreased glucose tolerance. We observed that treadmill exercise-training in high-fat fed mice resulted in a reduction in the lipid content in the liver, but not in muscle...... that the current worldwide obesity epidemic has resulted in the increased prevalence of “metabolic disease clusters”, including type 2 diabetes, fatty liver disease and dyslipidemia. Excessive plasma lipids can result in the accumulation of lipid metabolites at ectopic sites including skeletal muscle and liver...... during isolated muscle contractions. On the contrary, previous observations suggest that a permanent relocation of FAT/CD36 protein to the sarcolemma induces intracellular lipid accumulation, resulting in insulin resistance. Therefore, FAT/CD36 has been linked to insulin resistance. Whether increased FAT...

  5. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation

    DEFF Research Database (Denmark)

    Andreasen, Camilla H; Stender-Petersen, Kirstine L; Mogensen, Mette S

    2008-01-01

    (-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive...... homozygous risk A-allele carriers had a 1.95 +/- 0.3 kg/m(2) increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS: We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical......OBJECTIVE: Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes...

  6. Visceral fat accumulation in obese subjects : relation to energy expenditure and response to weight loss

    NARCIS (Netherlands)

    Leenen, R; van der Kooy, K; Deurenberg, P.; Seidell, J C; Weststrate, J A; Schouten, F J; Hautvast, J.G.A.J.

    1992-01-01

    Seventy-eight healthy obese subjects, 40 premenopausal women and 38 men aged 27-51 yr received a 4.2 MJ/day energy-deficit diet for 13 wk. Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) were measured by indirect calorimetry. Abdominal subcutaneous and visceral fat areas were

  7. Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Kosuke Matsuo

    2011-01-01

    Full Text Available Protein-tyrosine phosphatase 1B (PTP1B is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A and sumoylation-resistant (K/R PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR and insulin receptor substrate 1 (IRS1 tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B.

  8. Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood.

    Science.gov (United States)

    Baars, Annemarie; Oosting, Annemarie; Engels, Eefje; Kegler, Diane; Kodde, Andrea; Schipper, Lidewij; Verkade, Henkjan J; van der Beek, Eline M

    2016-06-01

    Epidemiological studies have demonstrated protective effects of breast-feeding on childhood obesity. Differences between human milk and infant milk formula (IMF) in dietary lipid structure may contribute to this effect. In our mouse model, feeding a diet containing large lipid droplets coated with phospholipids (PL) (Nuturis®; PL of milk fat globule membrane (MFGM) fraction origin) in early life protected against excessive body fat accumulation following a diet challenge in adult life. We now set out to determine the relevance of increased droplet size and/or MFGM lipid droplet coating to the observed anti-obesogenic effects in adult life. From day 16 to 42, male mouse pups were exposed to diets with small (S) or large (L) lipid droplets (0·3 v. 2·9 µm average mode diameter, respectively), either without MFGM or with MFGM coating around the lipid droplet, resulting in four groups: S (control diet), L, Scoating and Lcoating (Nuturis® IMF diet). Mice were subsequently challenged with a Western-style diet until dissection at postnatal day 98. A non-challenged group served as reference (REF). We repeatedly determined body composition between postnatal day 42 and 98. At day 98 plasma and gene expression measurements were performed. Only the Nuturis® IMF diet (Lcoating) in early life containing MFGM-coated large lipid droplets reduced body fat mass to a level comparable with the REF group. These data support the notion that the structural aspects of lipids in human milk, for example, both lipid droplet size as well as the MFGM coating, may contribute to its reported protective effect against obesity in later life.

  9. Sugar versus fat: elimination of glycogen storage improves lipid accumulation in Yarrowia lipolytica.

    Science.gov (United States)

    Bhutada, Govindprasad; Kavšcek, Martin; Ledesma-Amaro, Rodrigo; Thomas, Stéphane; Rechberger, Gerald N; Nicaud, Jean-Marc; Natter, Klaus

    2017-05-01

    Triacylglycerol (TAG) and glycogen are the two major metabolites for carbon storage in most eukaryotic organisms. We investigated the glycogen metabolism of the oleaginous Yarrowia lipolytica and found that this yeast accumulates up to 16% glycogen in its biomass. Assuming that elimination of glycogen synthesis would result in an improvement of lipid accumulation, we characterized and deleted the single gene coding for glycogen synthase, YlGSY1. The mutant was grown under lipogenic conditions with glucose and glycerol as substrates and we obtained up to 60% improvement in TAG accumulation compared to the wild-type strain. Additionally, YlGSY1 was deleted in a background that was already engineered for high lipid accumulation. In this obese background, TAG accumulation was also further increased. The highest lipid content of 52% was found after 3 days of cultivation in nitrogen-limited glycerol medium. Furthermore, we constructed mutants of Y. lipolytica and Saccharomyces cerevisiae that are deleted for both glycogen and TAG synthesis, demonstrating that the ability to store carbon is not essential. Overall, this work showed that glycogen synthesis is a competing pathway for TAG accumulation in oleaginous yeasts and that deletion of the glycogen synthase has beneficial effects on neutral lipid storage. © FEMS 2017.

  10. The influence of high fat diets with different ketogenic ratios on the hippocampal accumulation of creatine - FTIR microspectroscopy study

    Science.gov (United States)

    Skoczen, A.; Setkowicz, Z.; Janeczko, K.; Sandt, Ch.; Borondics, F.; Chwiej, J.

    2017-09-01

    The main purpose of this study was the determination and comparison of anomalies in creatine (Cr) accumulation occurring within CA3 and DG areas of hippocampal formation as a result of two high-fat, carbohydrate-restricted ketogenic diets (KD) with different ketogenic ratio (KR). To reach this goal, Fourier transformed infrared microspectroscopy with synchrotron radiation source (SRFTIR microspectroscopy) was applied for chemical mapping of creatine absorption bands, occurring around 1304, 1398 and 2800 cm- 1. The samples were taken from three groups of experimental animals: control group (N) fed with standard laboratory diet, KD1 and KD2 groups fed with high-fat diets with KR 5:1 and 9:1 respectively. Additionally, the possible influence on the phosphocreatine (PhCr, the high energetic form of creatine) content was evaluated by comparative analysis of chemical maps obtained for creatine and for compounds containing phosphate groups which manifest in the spectra at the wavenumbers of around 1240 and 1080 cm- 1. Our results showed that KD2 strongly modifies the frequency of Cr inclusions in both analyzed hippocampal areas. Statistical analysis, performed with Mann-Whitney U test revealed increased accumulation of Cr within CA3 and DG areas of KD2 fed rats compared to both normal rats and KD1 experimental group. Moreover, KD2 diet may modify the frequency of PhCr deposits as well as the PhCr to Cr ratio.

  11. The regulation of starch accumulation in Panicum maximum Jacq ...

    African Journals Online (AJOL)

    ... decrease the starch level. These observations are discussed in relation to the photosynthetic characteristics of P. maximum. Keywords: accumulation; botany; carbon assimilation; co2 fixation; growth conditions; mesophyll; metabolites; nitrogen; nitrogen levels; nitrogen supply; panicum maximum; plant physiology; starch; ...

  12. Tangeretin and 3',4',3,5,6,7,8-heptamethoxyflavone decrease insulin resistance, fat accumulation and oxidative stress in mice fed high-fat diet

    Science.gov (United States)

    Tangeretin and heptamethoxyflavone were investigated for their ability to repair metabolic damage caused by high-fat diet in C57BL/6J mice. In the first four weeks, induction of obesity was performed and the mice received standard diet (11% kcal from fat) or high-fat diet (45% kcal from fat). After ...

  13. Differential effects of restricted versus unlimited high-fat feeding in rats on fat mass, plasma hormones and brain appetite regulators.

    Science.gov (United States)

    Shiraev, T; Chen, H; Morris, M J

    2009-07-01

    The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague-Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile.

  14. [Dynamic accumulation regulation of curcumin, demethoxycurcumin and bisdemethoxyeurcumin in three strains of curcuma longae rhizome].

    Science.gov (United States)

    Li, Qing-Miao; Yang, Wen-Yu; Tang, Xue-Mei; Zhang, Mei; Zhou, Xian-Jian; Shu, Guang-Ming; Zhao, Jun-Ning; Fang, Qing-Mao

    2014-06-01

    The paper is aimed to study the dynamic accumulation regulation of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxyeurcumin (BDMC) in three strains of Curcuma longa, and provide scientific references for formalized cultivation, timely harvesting, quality control and breeding cultivation of C. longa. The accumulation regulation of the three curcumin derivatives was basically the same in rhizome of three strains. The relative contents decreased along with plant development growing, while the accumulation per hectare increased with plant development growing. The accumulation of curcuminoids per hectare could be taken as the assessment standard for the best harvest time of C. longa. A3 was the best strain in terms of Cur and BDMC content.

  15. Understanding the spatial formation and accumulation of fats, oils and grease deposits in the sewer collection system.

    Science.gov (United States)

    Dominic, Christopher Cyril Sandeep; Szakasits, Megan; Dean, Lisa O; Ducoste, Joel J

    2013-01-01

    Sanitary sewer overflows are caused by the accumulation of insoluble calcium salts of fatty acids, which are formed by the reaction between fats, oils and grease (FOG) and calcium found in wastewaters. Different sewer structural configurations (i.e., manholes, pipes, wet wells), which vary spatially, along with other obstructions (roots intrusion) and pipe deformations (pipe sags), may influence the detrimental buildup of FOG deposits. The purpose of this study was to quantify the spatial variation in FOG deposit formation and accumulation in a pilot-scale sewer collection system. The pilot system contained straight pipes, manholes, roots intrusion, and a pipe sag. Calcium and oil were injected into the system and operated at alkaline (pH = 10) and neutral (pH = 7) pH conditions. Results showed that solid accumulations were slightly higher at neutral pH. Fourier transform infrared (FTIR) analysis on the solids samples confirmed that the solids were indeed calcium-based fatty acid salts. However, the fatty acid profiles of the solids deviated from the profile found from FOG deposits in sewer systems, which were primarily saturated fatty acids. These results confirm the work done previously by researchers and suggest an alternative fate of unsaturated fatty acids that does not lead to their incorporation in FOG deposits in full-scale sewer systems.

  16. Supplementation with Vitis vinifera L. skin extract improves insulin resistance and prevents hepatic lipid accumulation and steatosis in high-fat diet-fed mice.

    Science.gov (United States)

    Santos, Izabelle Barcellos; de Bem, Graziele Freitas; Cordeiro, Viviane Silva Cristino; da Costa, Cristiane Aguiar; de Carvalho, Lenize Costa Reis Marins; da Rocha, Ana Paula Machado; da Costa, Gisele França; Ognibene, Dayane Teixeira; de Moura, Roberto Soares; Resende, Angela Castro

    2017-07-01

    Nonalcoholic fatty liver disease is one of the most common complications of obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source of polyphenols, which are related to its antioxidant and antihyperglycemic activities. We hypothesized that ACH09 could also exert beneficial effects on metabolic disorders associated with obesity and evaluated ACH09's influence on high-fat (HF) diet-induced hepatic steatosis and insulin resistance in C57BL/6 mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60% fat, HF) with or without ACH09 (200mg/[kg d]) for 12weeks. Our results showed that ACH09 reduced HF diet-induced body weight gain, prevented hepatic lipid accumulation and steatosis, and improved hyperglycemia and insulin resistance. The underlying mechanisms of these beneficial effects of ACH09 may involve the activation of hepatic insulin-signaling pathway because the expression of phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase, phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was increased by ACH09 and correlated with improvement of hyperglycemia, hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the lipogenic factor sterol regulatory-element binding protein-1c in the liver and upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated adenosine-monophosphate-activated protein kinase), which was associated with normal hepatic levels of triglyceride and cholesterol and prevention of steatosis. ACH09 prevented the hepatic oxidative damage in HF diet-fed mice probably by restoration of antioxidant activity. In conclusion, ACH09 protected mice from HF diet-induced obesity, insulin resistance, and hepatic steatosis. The regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative stress may contribute to ACH09's protective effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. TOR (target of rapamycin) is a key regulator of triacylglycerol accumulation in microalgae.

    Science.gov (United States)

    Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

    2016-01-01

    Most microalgae abundantly accumulate lipid droplets (LDs) containing triacylglycerols (TAGs) under several stress conditions, but the underlying molecular mechanism of this accumulation remains unclear. In a recent study, we found that inhibition of TOR (target of rapamycin), a highly conserved protein kinase of eukaryotes, by rapamycin resulted in TAG accumulation in microalgae, indicating that TOR negatively regulates TAG accumulation. Here, we show that formation of intracellular LDs and TAG accumulation were also induced in the unicellular green alga Chlamydomonas reinhardtii after exposure to Torin1 or AZD8055, which are novel TOR inhibitors that inhibit TOR activity in a manner different from rapamycin. These results supported quite well our previous conclusion that TOR is a central regulator of TAG accumulation in microalgae.

  18. Factors regulating fat oxidation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiens, Bente; Alsted, Thomas Junker; Jeppesen, Jacob

    2011-01-01

    In modern societies, oversupply of calories leads to obesity and chronic metabolic stress, which may lead to development of disease. Oversupply of calories is often associated with elevated plasma lipid concentrations and accumulation of lipids in skeletal muscle leading to decreased insulin...

  19. Effects of Exercise Training on Molecular Markers of Lipogenesis and Lipid Partitioning in Fructose-Induced Liver Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Siham Yasari

    2012-01-01

    Full Text Available The present study was designed to investigate the impact of exercise training on lipogenic gene expression in liver and lipid partitioning following the ingestion of a high fructose load. Female rats were exercise-trained for 8 wk or kept sedentary before being submitted to a fasting/refeeding protocol. Rats were further subdivided as follow: rats were fasted for 24 h, refed a standard diet for 24 h, starved for another 24 h, and refed with a standard or a high-fructose diet 24 h before sacrifice. Fructose refeeding was associated with an increase in hepatic lipid content, endocannabinoid receptor 1, sterol regulatory element-binding protein1c, and stearoyl-CoA desaturase1 gene expression in both Sed and TR rats. However, desaturation indexes measured in liver (C16 : 1/C16 : 0 and C18 : 1/C18 : 0 and plasma (C18 : 1/C18 : 0 were higher (P<0.01 in TR than in Sed rats following fructose refeeding. It is concluded that exercise training does not significantly affect fat accumulation and the molecular expression of genes involved in lipogenesis after fasting and fructose refeeding but does modify the partitioning of lipids so as to provide more unsaturated fatty acids in liver without affecting liver fat content.

  20. l-Leucine Supplementation Worsens the Adiposity of Already Obese Rats by Promoting a Hypothalamic Pattern of Gene Expression that Favors Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Thais T. Zampieri

    2014-04-01

    Full Text Available Several studies showed that l-leucine supplementation reduces adiposity when provided before the onset of obesity. We studied rats that were exposed to a high-fat diet (HFD for 10 weeks before they started to receive l-leucine supplementation. Fat mass was increased in l-leucine-supplemented rats consuming the HFD. Accordingly, l-leucine produced a hypothalamic pattern of gene expression that favors fat accumulation. In conclusion, l-leucine supplementation worsened the adiposity of rats previously exposed to HFD possibly by central mechanisms.

  1. Vitamin D prevents lipid accumulation in murine muscle through regulation of PPARγ and perilipin-2 expression.

    Science.gov (United States)

    Li, Jiarong; Mihalcioiu, Milton; Li, Lifeng; Zakikhani, Mahvash; Camirand, Anne; Kremer, Richard

    2018-03-01

    Vitamin D plays an important role in regulation of skeletal muscle tone and contraction. Serum vitamin D status is linked to muscle power and force in adolescent girls, and vitamin D deficiency is associated with myopathies in children and poorer physical performance in the elderly. We previously reported that vitamin D deficiency is linked to a significant increase in muscle fatty infiltration in healthy young women, and studies in patients with neuromuscular disorders also associate muscle weakening and lipid content. In order to better understand the link between vitamin D status and skeletal muscle lipid metabolism, we compared the effect of a low (25IU/kg) or normal (1000IU/kg) vitamin D 3 diet on muscle fat in female FVB mice maintained in a room without UVB lighting to minimize endogenous vitamin D production. Animals on low vitamin D diet displayed lower circulating 25(OH)D levels and a dramatic increase (287±52% compared to normal diet, p<0.0001) in lipid deposition in skeletal muscle accompanied by muscle fiber disorganization. Lipid droplet staining increased by 242±23% (p<0.0001) in low vitamin D diet, and lipid droplet coat protein perilipin-2 and nuclear receptor transcription factor PPARγ expression levels were increased compared to mice fed the normal vitamin D diet: average staining for PLIN2: 0.22±0.08 (25IU/kg diet) vs 0.10±0.02 (1000IU/kg). Average staining for PPARγ: 0.24±0.06 (25IU/kg diet) vs 0.07±0.04 (1000IU/kg) p<0.0001. Tissue mass spectrometry imaging revealed major differences in muscle phospholipids profile depending on diet. In vitro, 1,25(OH) 2 D 3 treatment of 3T3-L1 pre-adipocytes inhibited appearance of lipid droplets by 79±9.3%, and caused a 80±10% and 25±8% (p=0.001) reduction in PPARγ and perilipin-2 mRNA levels (by qPCR) compared to control cells. In summary, we report here the first in vivo model illustrating the important structural muscle fiber disorganization and fat accumulation inside and outside muscle

  2. Genetic regulation of glucoraphanin accumulation in Beneforté broccoli.

    Science.gov (United States)

    Traka, Maria H; Saha, Shikha; Huseby, Stine; Kopriva, Stanislav; Walley, Peter G; Barker, Guy C; Moore, Jonathan; Mero, Gene; van den Bosch, Frans; Constant, Howard; Kelly, Leo; Schepers, Hans; Boddupalli, Sekhar; Mithen, Richard F

    2013-06-01

    · Diets rich in broccoli (Brassica oleracea var italica) have been associated with maintenance of cardiovascular health and reduction in risk of cancer. These health benefits have been attributed to glucoraphanin that specifically accumulates in broccoli. The development of broccoli with enhanced concentrations of glucoraphanin may deliver greater health benefits. · Three high-glucoraphanin F1 broccoli hybrids were developed in independent programmes through genome introgression from the wild species Brassica villosa. Glucoraphanin and other metabolites were quantified in experimental field trials. Global SNP analyses quantified the differential extent of B. villosa introgression · The high-glucoraphanin broccoli hybrids contained 2.5-3 times the glucoraphanin content of standard hybrids due to enhanced sulphate assimilation and modifications in sulphur partitioning between sulphur-containing metabolites. All of the high-glucoraphanin hybrids possessed an introgressed B. villosa segment which contained a B. villosa Myb28 allele. Myb28 expression was increased in all of the high-glucoraphanin hybrids. Two high-glucoraphanin hybrids have been commercialised as Beneforté broccoli. · The study illustrates the translation of research on glucosinolate genetics from Arabidopsis to broccoli, the use of wild Brassica species to develop cultivars with potential consumer benefits, and the development of cultivars with contrasting concentrations of glucoraphanin for use in blinded human intervention studies. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  3. Determinant factors of the severity of carotid atherosclerosis in relation to accumulation of visceral fat in type 2 diabetic subjects

    International Nuclear Information System (INIS)

    Konishi, Kazunori

    2006-01-01

    Our aim was to verify the possible association of visceral fat accumulation with the severity of carotid atherosclerosis in order to clarify practical and feasible determinants for each parameter of atherosclerosis in type 2 diabetic subjects. The subjects studied were consecutive 151 diabetic subjects and age-matched 83 nondiabetic subjects, with no history of atherosclerotic disease. All subjects gave written informed consent to participate in the study. Subcutaneous and visceral fat areas on a CT scan at the level of the umbilicus were measured. Ambulatory 24-h blood pressure (BP) was recorded. Pulse pressure (PP) was defined as systolic BP (sBP) minus diastolic BP (dBP). Stiffness index β as a functional change and intima-media thickness (IMT) and plaque formation as structural changes were measured by echo-Doppler examinations of the carotid arteries. Insulin sensitivity was estimated by homeostasis model assessment for insulin resistance (HOMA-IR). Serum levels of adiponectin and tumor necrosis factor (TNF)-α were determined. Male gender, HbAlc, HOMA-IR and serum nonHDL-cholesterol (C) were higher, and visceral fat area was larger in the diabetic subjects than in the nondiabetic subjects. Serum adiponectin and TNF-α levels were similar between the two groups, while the TNF-α/adiponectin ratio in the diabetic subjects was significantly higher than that in the nondiabetic subjects. The IMT was thicker, and the stiffness index β was higher in the diabetic subjects than those in the nondiabetic subjects. These differences still remained highly significant after adjusting for age, sex and 24-h sBP. Plaque formation was also severer in the diabetic subjects than in the nondiabetic subjects. Visceral fat areas were correlated negatively with serum adiponectin levels, and positively with TNF-α/adiponectin ratio and serum nonHDL-C in diabetic subjects. The nighttime PP was associated with IMT, stiffness index β and the degree of plaque formation independently

  4. Regulation of body fat mass by the gut microbiota

    DEFF Research Database (Denmark)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik

    2016-01-01

    New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries...

  5. The effect of natural antioxidants on the rate of accumulation of oxidation products in the fat phase of butter cream

    Directory of Open Access Journals (Sweden)

    M. S. Voronina

    2016-01-01

    Full Text Available Describes the main finishing prefabricated pastries and cakes-cream. Researched range of cream depending on the fruit components and method of production. Aim: to study the degree of oxidation cream with natural antioxidants from fruits and berries processing products, namely in the form of concentrated juice of fruits and berries. Outlines the process of oxidation of lipids, one of the fundamental processes of loss of quality food products. Describes the action of antioxidants as antioxidants on accumulation intensity concentrations of primary and secondary oxidation products, making the final product unsuitable for the consumer and the bounding its shelf life. Presents the results of a study of the contents of primary and secondary oxidation products in butter cream immediately after cooking, as well as samples, stored for five days with the addition of antioxidants in the form of concentrated juice of fruits and berries in the amount of 2–7% by weight of cream. As a control sample has been used cream with no additives. Quality indicators to characterize the degree of oxidation of the product: acid, peroxide, anizidin and tioburbit number. The study found that adding a concentrated juice of fruits and berries as antioxidant in recipe cream reduces the growth rate of the concentration of free fatty acids on the fifth day, as compared with the reference sample. Adding concentrated juice of fruits and berries slows down the process of dissolution of the fat molecules in fat fraction of cream with the formation of free fatty acids; intensity decay reaction of peroxides and hydroxides slows down and, consequently, decreases the formation of aldehydes, deteriorating the taste and smell of the cream; quantitatively reduced the growth of education malondial′degida.

  6. Deleted in Breast Cancer 1 Limits Adipose Tissue Fat Accumulation and Plays a Key Role in the Development of Metabolic Syndrome Phenotype

    NARCIS (Netherlands)

    Escande, Carlos; Nin, Veronica; Pirtskhalava, Tamar; Chini, Claudia C. S.; Tchkonia, Tamar; Kirkland, James L.; Chini, Eduardo N.

    Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus and that it is only when the maximum fat accumulation capacity is reached and fatty acid

  7. Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat

    Directory of Open Access Journals (Sweden)

    Lu Yao

    2017-07-01

    Full Text Available Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a β-adrenergic agonist. Deletion of SIRT6 in adipose tissue impairs the thermogenic function of brown adipocytes, causing a morphological “whitening” of brown fat, reduced oxygen (O2 consumption, obesity, decreased core body temperature, and cold sensitivity. Fat SIRT6-deleted mice exhibit increased blood glucose levels, severe insulin resistance, and hepatic steatosis. Moreover, SIRT6 deficiency inhibits the browning of white adipose tissue (WAT following cold exposure or β3-agonist treatment. Depletion of SIRT6 expression in brown adipocytes reduces expression of thermogenic genes, causing a reduction in cellular respiration. Conversely, SIRT6 overexpression in primary fat cells stimulates the thermogenic program. Mechanistically, SIRT6 interacts with and promotes phospho-ATF2 binding to the PGC-1α gene promoter to activate its expression. The present study reveals a critical role for SIRT6 in regulating thermogenesis of fat.

  8. The Influence of Abdominal and Ectopic Fat Accumulation on Carotid Intima-Media Thickness: A Chongqing Study.

    Science.gov (United States)

    Yi, Xu; Liu, Yu-Hui; Zhou, Xin-Fu; Wang, Yan-Jiang; Deng, Juan; Liu, Juan; He, Hong-Bo; Xu, Zhi-Qiang

    2018-04-16

    To investigate the effects of abdominal obesity (AO) and nonalcoholic fatty liver disease (NAFLD) with or without AO on carotid arteries by determining carotid intima-media thickness (CIMT). A total of 2745 Chinese Han adults (aged between 40 and 50 years old) were recruited and divided into 4 groups: (1) NW-no NAFL group: the normal body weight without NAFLD (n = 1888); (2) AO-no NAFL group: AO without NAFLD (n = 259); (3) NW-with NAFL group: NAFLD without AO (n = 93); and (4) AO-with NAFL group: AO with NAFLD (n = 505). The CIMT rate of each group was compared among 4 groups and the regression analysis was further used to correct confounders. We found that the NW-with NAFL group had a significantly higher CIMT rate than the AO-no NAFL group ([.87 ± .31] versus [.72 ± .29] P < .01) and the AO-with NAFL group ([.87 ± .31] versus [.79 ± .26], P < .01). The ectopic liver fat accumulation may increase the risk of atherosclerosis. Therefore, screening NAFLD in the population with normal weight may be beneficial for the prevention of atherosclerosis at an early stage. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Novel function of the retinoblastoma protein in fat: regulation of white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; te Riele, Hein; Kristiansen, Karsten

    2004-01-01

    the major energy store and brown adipocytes being potent energy-dissipaters through thermogenesis. Yet, little is known about factors differentially regulating the formation of white and brown fat cells. Members of the retinoblastoma protein family (pRB, p107, p130) have been implicated in the regulation...... of adipocyte differentiation, and expression and phosphorylation of the three retinoblastoma family proteins oscillate in a characteristic manner during differentiation of the white preadipocyte cell line 3T3-L1. We have recently demonstrated a surprising function of the retinoblastoma protein...... in the regulation of white versus brown adipocyte differentiation in vitro and possibly in vivo. Here we summarize the current knowledge on the retinoblastoma protein in fat cells, with particular emphasis on its potential role in adipocyte lineage commitment and differentiation....

  10. Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis

    OpenAIRE

    Lin, Heng-Hsu; Lee, Jen-Kuang; Yang, Chung-Yi; Lien, Yu-Chung; Huang, Jenq-Wen; Wu, Cho-Kai

    2013-01-01

    Background Symptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population....

  11. Regulation of carotenoid and ABA accumulation during the development and germination of Nicotiana plumbaginifolia seeds.

    Science.gov (United States)

    Frey, Anne; Boutin, Jean-Pierre; Sotta, Bruno; Mercier, Raphaël; Marion-Poll, Annie

    2006-08-01

    Abscisic acid (ABA) is derived from epoxycarotenoid cleavage and regulates seed development and maturation. A detailed carotenoid analysis was undertaken to study the contribution of epoxycarotenoid synthesis to the regulation of ABA accumulation in Nicotiana plumbaginifolia developing seeds. Maximal accumulation of xanthophylls occurred at mid-development in wild type seeds, when total ABA levels also peaked. In contrast, in ABA-deficient mutants xanthophyll synthesis was delayed, in agreement with the retardation in seed maturation. Seed dormancy was restored in mutants impaired in the conversion of zeaxanthin into violaxanthin by zeaxanthin epoxidase (ZEP), by the introduction of the Arabidopsis AtZEP gene under the control of promoters inducing expression during later stages of seed development compared to wild type NpZEP, and in dry and imbibed seeds. Alterations in the timing and level of ZEP expression did not highly affect the temporal regulation of ABA accumulation in transgenic seeds, despite notable perturbations in xanthophyll accumulation. Therefore, major regulatory control of ABA accumulation might occur downstream of epoxycarotenoid synthesis.

  12. Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by {sup 1}H magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Krssak, Martin [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); Hofer, Harald [Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Wrba, Fritz [Department of Clinical Pathology, Medical University of Vienna (Austria); Meyerspeer, Martin [MR Centre-of-Excellence, Department of Radiodiagnostics, Medical University of Vienna (Austria); Center for Biomedical Engineering and Physics, Medical University of Vienna (Austria); Brehm, Attila [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center of Diabetes Research and Department of Medicine/Metabolic Diseases, Heinrich Heine University, Duesseldorf (Germany); Lohninger, Alfred [Department of Medical Chemistry, Center for Physiology and Pathophysiology, Medical University of Vienna (Austria); Steindl-Munda, Petra [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); MR Centre-of-Excellence, Department of Radiodiagnostics, Medical University of Vienna (Austria); Moser, Ewald [MR Centre-of-Excellence, Department of Radiodiagnostics, Medical University of Vienna (Austria); Center for Biomedical Engineering and Physics, Medical University of Vienna (Austria); Ferenci, Peter [Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Roden, Michael, E-mail: michael.roden@ddz.uni-duesseldorf.d [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center of Diabetes Research and Department of Medicine/Metabolic Diseases, Heinrich Heine University, Duesseldorf (Germany)

    2010-06-15

    Background: Liver biopsy is the standard method for diagnosis of hepatic steatosis, but is invasive and carries some risk of morbidity. Aims and methods: Quantification of hepatocellular lipid content (HCL) with non-invasive single voxel {sup 1}H magnetic resonance spectroscopy (MRS) at 3 T was compared with histological grading and biochemical analysis of liver biopsies in 29 patients with chronic hepatitis C. Body mass index, indices of insulin resistance (homeostasis model assessment index, HOMA-IR), serum lipids and serum liver transaminases were also quantified. Results: HCL as assessed by {sup 1}H MRS linearly correlated (r = 0.70, p < 0.001) with histological evaluation of liver biopsies and was in agreement with histological steatosis staging in 65% of the patients. Biochemically assessed hepatic triglyceride contents correlated with HCL measured with {sup 1}H MRS (r = 0.63, p < 0.03) and allowed discriminating between none or mild steatosis versus moderate or severe steatosis. Patients infected with hepatitis C virus genotype 3 had a higher prevalence of steatosis (62%) which was not explained by differences in body mass or whole body insulin resistance. When these patients were excluded from correlation analysis, hepatic fat accumulation positively correlated with insulin resistance in the remaining hepatitis C patients (HCL vs. HOMA-IR, r = 0.559, p < 0.020, n = 17). Conclusion: Localized {sup 1}H MRS is a valid and useful method for quantification of HCL content in patients with chronic hepatitis C and can be easily applied to non-invasively monitoring of steatosis during repeated follow-up measurements in a clinical setting.

  13. The fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms improves insulin resistance and hepatic lipid accumulation by modulation of liver adenosine monophosphate-activated protein kinase activity and lipogenic gene expression in high-fat diet-fed obese mice.

    Science.gov (United States)

    Saito, Tetsuo; Nishida, Miyako; Saito, Masafumi; Tanabe, Akari; Eitsuka, Takahiro; Yuan, Shi-Hua; Ikekawa, Nobuo; Nishida, Hiroshi

    2016-10-01

    Obesity-associated insulin resistance is a major risk factor for most metabolic diseases, including dyslipidemia and type 2 diabetes. Acanthopanax senticosus (Rupr. et Maxim.) Harms (Goka) root has been used in traditional Chinese medicine for treatment of diabetes and other conditions; however, little is known about the effects of Goka fruit (GF). Goka fruit is rich in anthocyanin, which has beneficial effects on obesity and insulin resistance via activation of adenosine monophosphate-activated protein kinase (AMPK). We hypothesized that GF can improve obesity-associated insulin resistance. The aim of the present study was to investigate whether GF improves insulin resistance in high-fat diet (HFD)-induced obese mice. High-fat diet mice treated with GF (500 and 1000 mg/kg) for 12 weeks showed an improved glucose tolerance and insulin sensitivity, as well as reduced plasma insulin and liver lipid accumulation. Moreover, GF administration to HFD mice resulted in down-regulation of fatty acid synthase expression and up-regulation of cholesterol 7-alpha-hydroxylase expression in the liver. Notably, AMPK phosphorylation in the liver increased after GF administration. In summary, GF supplementation improved obesity-associated insulin resistance and hepatic lipid accumulation through modulation of AMPK activity and lipid metabolism-associated gene expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Rehrer, N J; Pilegaard, H

    2007-01-01

    AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were...... exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes....

  15. Photosynthesis down-regulation precedes carbohydrate accumulation under sink limitation in Citrus.

    Science.gov (United States)

    Nebauer, Sergio G; Renau-Morata, Begoña; Guardiola, José Luis; Molina, Rosa-Victoria

    2011-02-01

    Photosynthesis down-regulation due to an imbalance between sources and sinks in Citrus leaves could be mediated by excessive accumulation of carbohydrates. However, there is limited understanding of the physiological role of soluble and insoluble carbohydrates in photosynthesis regulation and the elements triggering the down-regulation process. In this work, the role of non-structural carbohydrates in the regulation of photosynthesis under a broad spectrum of source-sink relationships has been investigated in the Salustiana sweet orange. Soluble sugar and starch accumulation in leaves, induced by girdling experiments, did not induce down-regulation of the photosynthetic rate in the presence of sinks (fruits). The leaf-to-fruit ratio did not modulate photosynthesis but allocation of photoassimilates to the fruits. The lack of strong sink activity led to a decrease in the photosynthetic rate and starch accumulation in leaves. However, photosynthesis down-regulation due to an excess of total soluble sugars or starch was discarded because photosynthesis and stomatal conductance reduction occurred prior to any significant accumulation of these carbohydrates. Gas exchange and fluorescence parameters suggested biochemical limitations to photosynthesis. In addition, the expression of carbon metabolism-related genes was altered within 24 h when strong sinks were removed. Sucrose synthesis and export genes were inhibited, whereas the expression of ADP-glucose pyrophosphorylase was increased to cope with the excess of assimilates. In conclusion, changes in starch and soluble sugar turnover, but not sugar content per se, could provide the signal for photosynthesis regulation. In these conditions, non-stomatal limitations strongly inhibited the photosynthetic rate prior to any significant increase in carbohydrate levels.

  16. Milk production and composition, and progeny performance in young ewes with high merit for rapid growth and muscle and fat accumulation.

    Science.gov (United States)

    Rosales Nieto, C A; Ferguson, M B; Macleay, C A; Briegel, J R; Wood, D A; Martin, G B; Bencini, R; Thompson, A N

    2018-02-26

    In ewe lambs, acceleration of growth and accumulation of both muscle and fat leads to earlier sexual maturity and better reproductive performance. The next stage in the development of this theme is to test whether these aspects of growth in young ewes affect milk production in their first lactation and the growth of their first progeny. We studied 75 young Merino ewes that had known phenotypic values for depth of eye muscle (EMD) and fat (FAT), and known Australian Sheep Breeding Values for post-weaning weight (PWT) and depths of eye muscle (PEMD) and fat (PFAT). They lambed for the first time at 1 year of age. Their lambs were weighed weekly from birth to weaning at 10 weeks to determine live weight gain and weaning weight. Progeny birth weight was positively associated with live weight gain and weaning weight (P0.05). The PWT of the sire was positively associated with live weight gain (P0.05). The concentrations of fat, protein, lactose and total solids in the milk were not affected by the phenotype or genotype of the mothers or of the sires of the mothers, or by the sex of the progeny (P>0.05). We conclude that selection of young Merino ewes for better growth, and more rapid accumulation of muscle and fat, will lead to progeny that are heavier at birth, grow faster and are heavier at weaning. Moreover, milk production and composition do not seem to be affected by the genetic merit of the mother for post-weaning live weight or PEMD or PFAT. Therefore, Merino ewes can lamb at 1 year of age without affecting the production objectives of the Merino sheep industry.

  17. Ananas comosus L. Leaf Phenols and p-Coumaric Acid Regulate Liver Fat Metabolism by Upregulating CPT-1 Expression

    Directory of Open Access Journals (Sweden)

    Weidong Xie

    2014-01-01

    Full Text Available In this study, we aimed to investigate the effect and action mechanisms of pineapple leaf phenols (PLPs on liver fat metabolism in high-fat diet-fed mice. Results show that PLP significantly reduced abdominal fat and liver lipid accumulation in high-fat diet-fed mice. The effects of PLP were comparable with those of FB. Furthermore, at the protein level, PLP upregulated the expression of carnitine palmitoyltransferase 1 (CPT-1, whereas FB had no effects on CPT-1 compared with the HFD controls. Regarding mRNA expression, PLP mainly promoted the expression of CPT-1, PGC1a, UCP-1, and AMPK in the mitochondria, whereas FB mostly enhanced the expression of Ech1, Acox1, Acaa1, and Ehhadh in peroxisomes. PLP seemed to enhance fat metabolism in the mitochondria, whereas FB mainly exerted the effect in peroxisomes. In addition, p-coumaric acid (CA, one of the main components from PLP, significantly inhibited fat accumulation in oleic acid-induced HepG2 cells. CA also significantly upregulated CPT-1 mRNA and protein expressions in HepG2 cells. We, firstly, found that PLP enhanced liver fat metabolism by upregulating CPT-1 expression in the mitochondria and might be promising in treatment of fatty liver diseases as alternative natural products. CA may be one of the active components of PLP.

  18. lgl Regulates the Hippo Pathway Independently of Fat/Dachs, Kibra/Expanded/Merlin and dRASSF/dSTRIPAK

    Energy Technology Data Exchange (ETDEWEB)

    Parsons, Linda M., E-mail: parsonsl@unimelb.edu.au [Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002 (Australia); Department of Genetics, University of Melbourne, Melbourne, Victoria 3010 (Australia); Grzeschik, Nicola A. [Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002 (Australia); Richardson, Helena E., E-mail: n.a.grzeschik@umcg.nl [Cell Cycle and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002 (Australia); Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3010 (Australia); Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria 3010 (Australia); Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Victoria 3010 (Australia); Present address: Department of Cell Biology, University Medical Centre Groningen, Groningen (Netherlands)

    2014-04-16

    In both Drosophila and mammalian systems, the Hippo (Hpo) signalling pathway controls tissue growth by inhibiting cell proliferation and promoting apoptosis. The core pathway consists of a protein kinase Hpo (MST1/2 in mammals) that is regulated by a number of upstream inputs including Drosophila Ras Association Factor, dRASSF. We have previously shown in the developing Drosophila eye epithelium that loss of the apico-basal cell polarity regulator lethal-(2)-giant-larvae (lgl), and the concomitant increase in aPKC activity, results in ectopic proliferation and suppression of developmental cell death by blocking Hpo pathway signalling. Here, we further explore how Lgl/aPKC interacts with the Hpo pathway. Deregulation of the Hpo pathway by Lgl depletion is associated with the mislocalization of Hpo and dRASSF. We demonstrate that Lgl/aPKC regulate the Hpo pathway independently of upstream inputs from Fat/Dachs and the Kibra/Expanded/Merlin complex. We show depletion of Lgl also results in accumulation and mislocalization of components of the dSTRIPAK complex, a major phosphatase complex that directly binds to dRASSF and represses Hpo activity. However, depleting dSTRIPAK components, or removal of dRASSF did not rescue the lgl{sup −/−} or aPKC overexpression phenotypes. Thus, Lgl/aPKC regulate Hpo activity by a novel mechanism, independently of dRASSF and dSTRIPAK. Surprisingly, removal of dRASSF in tissue with increased aPKC activity results in mild tissue overgrowth, indicating that in this context dRASSF acts as a tumor suppressor. This effect was independent of the Hpo and Ras Mitogen Activated Protein Kinase (MAPK) pathways, suggesting that dRASSF regulates a novel pathway to control tissue growth.

  19. SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing inflammation, oxidative stress and lipid accumulation.

    Science.gov (United States)

    Pan, Zhen-Guo; An, Xu-Sheng

    2018-04-06

    SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice. Additionally, inflammatory response caused by HFD was alleviated by SARM1-deletion through inactivating TLR4/7/9 and nuclear factor kappa B (NF-κB) pathways. Of note, SARM1-deletion also reduced the expressions of inflammation-associated molecules in hypothalamus of HFD-fed mice. Furthermore, HFD administration led to oxidative stress in liver of mice, while being decreased in SARM1-KO mice. Moreover, SARM1-ablation improved lipid dyslipidemia by suppressing the mRNA levels of genes, linked to glycolysis, lipogenesis and transcriptional regulation. Insulin resistance was also attenuated by SARM1-deficiency through enhancing the activation of liver Akt/glycogen synthase kinase-3β (GSK3β) and insulin receptor substrate-1 (IRS1)/FOXO1 pathways in HFD-fed mice. Also, SARM1-knockout improved neuropeptide Y (NPY), Pro-Opiomelanocortins (POMC), Agouti-related Protein (AGRP) and Cocaine-and-Amphetamine Responsive Transcript 1 (CART1) expressions in hypothalamus of mice after HFD administration. In vitro, we found that the reduction of inflammatory response, oxidative stress and dyslipidemia induced by SARM1-knockout in primary hepatocytes after fructose stimulation was largely attributed to its suppression to TLR4/7/9. Together, the findings demonstrated that SARM1 might be an effective target for developing effective therapeutic strategies against NAFLD. Copyright © 2018

  20. Involvement of endogenous opiates in regulation of gastric emptying of fat test meals in mice

    International Nuclear Information System (INIS)

    Fioramonti, J.; Fargeas, M.J.; Bueno, L.

    1988-01-01

    The role of endogenous opioids and cholecystokinin (CCK) in gastric emptying was investigated in mice killed 30 min after gavage with 51 Cr-radiolabeled liquid meals. The meals consisted of 0.5 ml of milk or one of five synthetic meals containing arabic gum, glucose and/or arachis oil and/or casein. Naloxone (0.1 mg/kg sc) significantly (P less than 0.01) accelerated gastric emptying of milk and meals containing fat but did not modify gastric emptying of nonfat meals. The CCK antagonist asperlicin (0.1 mg/kg ip) increased by 25% gastric emptying of milk. The gastric emptying of meals containing glucose and casein but not fat was reduced after administration of the COOH-terminal octapeptide of cholecystokinin (CCK-8, 4 micrograms/kg ip). This decrease was antagonized by both asperlicin (10 mg/kg ip) and naloxone (0.1 mg/kg sc). Intracerebroventricular (icv) administration of an opiate antagonist that poorly crosses the blood-brain barrier, methyl levallorphan (10 micrograms/kg), did not modify gastric emptying of milk but accelerated it when peripherally administered (0.1 mg/kg sc). Similarly, asperlicin (icv) administered at a dose of 1 mg/kg did not affect milk emptying. These results indicate that endogenous opiates are involved at peripheral levels in the regulation of gastric emptying of fat meals only and that such regulation involves release of CCK

  1. Maternal fat-soluble vitamins, brain development, and regulation of feeding behavior: an overview of research.

    Science.gov (United States)

    Sánchez-Hernández, Diana; Anderson, G Harvey; Poon, Abraham N; Pannia, Emanuela; Cho, Clara E; Huot, Pedro S P; Kubant, Ruslan

    2016-10-01

    Recent research shows a link between vitamin intake during pregnancy and offspring health. Inadequate intakes of water-soluble vitamins during pregnancy lead to obesity and characteristics of the metabolic syndrome, concurrent with altered developments in food intake regulatory pathways. Few studies, however, have reported on the effects of fat-soluble vitamins (A, D, E, and K) on the development of food intake regulatory pathways. The majority of studies to date have focused on associations between inadequate and high intakes of folic acid and vitamin D and neurocognitive development of the offspring. Hence, the objective of this review is to present an evaluation of the role of maternal vitamins A, D, E, and K in brain development and function of neural pathways that regulate feeding behaviors. PubMed and Google Scholar were searched from 1975 through September, 2016. Most studies supporting a role for fat-soluble vitamins in regulating brain development and associated behaviors have been conducted in animal and cell models, leaving uncertain their relevance to neurocognitive development and function in humans. Nevertheless, although current research on defining the role of maternal fat-soluble vitamins in offspring's brain development is limited, it is sufficient to warrant further investigations on their impact when intake amounts during pregnancy are not only inadequate but also exceed requirements. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Transgenic UCP1 in white fat protects against lipid accumulation in skeletal muscle of mice fed a high-fat diet

    Czech Academy of Sciences Publication Activity Database

    Jeleník, Tomáš; Jílková, Zuzana; Slámová, Kristýna; Rossmeisl, Martin; Kopecký, Jan

    2007-01-01

    Roč. 50, Suppl.1 (2007), S321-S321 ISSN 0012-186X. [Annual Meeting of the European Association for the Study of Diabetes /43./. 18.09.2007-21.09.2007, Amsterdam] R&D Projects: GA ČR(CZ) GD303/03/H065 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * respiratory uncoupling * white fat * lipid metabolism Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Lili; Li, Jinmei [The Ministry of Education - MOE Key Laboratory for Standardization of Chinese Medicines, The State Administration of TCM - SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shanghai R& D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203 (China); Song, Baoliang; Xiao, Xu [The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Zhang, Binfeng; Qi, Meng [The Ministry of Education - MOE Key Laboratory for Standardization of Chinese Medicines, The State Administration of TCM - SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shanghai R& D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203 (China); Huang, Wendong [Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA (United States); Yang, Li, E-mail: yangli7951@hotmail.com [The Ministry of Education - MOE Key Laboratory for Standardization of Chinese Medicines, The State Administration of TCM - SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shanghai R& D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203 (China); and others

    2016-08-01

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

  5. The effects of Bee Venom and Sweet Bee Venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation

    OpenAIRE

    Min-Ki Kim; Si Hyeong, Lee; Jo Young Shin; Kang San Kim; Nam Guen Cho; Ki Rok Kwon; Tae Jin Rhim

    2007-01-01

    Objectives : The purpose of this study was to investigate the effects of Bee Venom and Sweet Bee Venom to the primary cultured preadipocyte, adipocytes, and localized fat tissue. Methods : Decreased preadipocyte proliferation and decreased lipogenesis are mechanisms to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures using Sprague-Dawley Rats and treated with 0.01-1mg/㎖ Bee Venom and Sweet Bee Venom. And porcine skin including fat tissue after treated Bee Ve...

  6. Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

    Energy Technology Data Exchange (ETDEWEB)

    Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei; Nicora, Carrie D.; Fillmore, Thomas L.; Purvine, Samuel O.; Webb-Robertson, Bobbie-Jo; Smith, Richard D.; Baker, Scott E.; Metz, Thomas O.; Nielsen, Jens; Lee, Sang Yup

    2017-06-20

    ABSTRACT

    The yeastYarrowia lipolyticais a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis inY. lipolyticaand identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination ofDGA1overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor.

    IMPORTANCEThe ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeastYarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors

  7. JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Guang-feng [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Xiao, Di; Gong, Wei-jing [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Hui-xia; Liu, Jun [Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Zhou, Hong-hao [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China)

    2014-03-14

    Highlights: • JAZF1 was significantly upregulated during the differentiation of 3T3-L1 preadipocytes. • JAZF1 overexpression inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes. • JAZF1 overexpression inhibited the expression of SREBP1, ACC, and FAS. • JAZF1 overexpression upregulated the expression of HSL and ATGL. • SREBP1 and JAZF1 could regulate each other in adipocytes. - Abstract: JAZF1 is a newly identified gene with unknown functions. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. Studies have demonstrated that JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear orphan receptor family members are involved in the regulation of lipid metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism. In this study, JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1 inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and significantly inhibited the expression of SREBPl, ACC, and FAS, which were important in lipid synthesis, while upregulating the expression of key enzyme hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory function on the expression of JAZF1. SREBP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes. Therefore, JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. This result suggests that JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders.

  8. JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes

    International Nuclear Information System (INIS)

    Ming, Guang-feng; Xiao, Di; Gong, Wei-jing; Liu, Hui-xia; Liu, Jun; Zhou, Hong-hao; Liu, Zhao-qian

    2014-01-01

    Highlights: • JAZF1 was significantly upregulated during the differentiation of 3T3-L1 preadipocytes. • JAZF1 overexpression inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes. • JAZF1 overexpression inhibited the expression of SREBP1, ACC, and FAS. • JAZF1 overexpression upregulated the expression of HSL and ATGL. • SREBP1 and JAZF1 could regulate each other in adipocytes. - Abstract: JAZF1 is a newly identified gene with unknown functions. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. Studies have demonstrated that JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear orphan receptor family members are involved in the regulation of lipid metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism. In this study, JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1 inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and significantly inhibited the expression of SREBPl, ACC, and FAS, which were important in lipid synthesis, while upregulating the expression of key enzyme hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory function on the expression of JAZF1. SREBP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes. Therefore, JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. This result suggests that JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders

  9. BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2014-01-01

    Full Text Available The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat and the age-matched control mice were fed with control diet (10% kcal as fat for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.

  10. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat

    International Nuclear Information System (INIS)

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-01-01

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. - Highlights: • The age-related AGE-albumin accumulation and S100β were more prominent in visceral than subcutaneous fat. • The age-related RAGE expression were more prominent in visceral than subcutaneous fat.

  11. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat

    Energy Technology Data Exchange (ETDEWEB)

    Son, Kuk Hui [Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon (Korea, Republic of); Son, Myeongjoo [Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon (Korea, Republic of); Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon (Korea, Republic of); Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji [Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon (Korea, Republic of); Choi, Chang Hu [Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon (Korea, Republic of); Park, Kook Yang, E-mail: kkyypark@ghil.com [Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon (Korea, Republic of); Byun, Kyunghee, E-mail: khbyun1@gachon.ac.kr [Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon (Korea, Republic of); Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon (Korea, Republic of)

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. - Highlights: • The age-related AGE-albumin accumulation and S100β were more prominent in visceral than subcutaneous fat. • The age-related RAGE expression were more prominent in visceral than subcutaneous fat.

  12. Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis.

    Science.gov (United States)

    Lin, Heng-Hsu; Lee, Jen-Kuang; Yang, Chung-Yi; Lien, Yu-Chung; Huang, Jenq-Wen; Wu, Cho-Kai

    2013-08-30

    Symptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population. This was a cross-sectional study of 149 patients with preserved left ventricular systolic function who were undergoing PD. LVDD was diagnosed (according to the European Society of Cardiology guidelines) and EpF thickness measured by echocardiography. The patients without LVDD were used as controls. The serum inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was measured. The location and amount of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, more visceral and peritoneal fat, and thicker EpF (all p EpF all correlated significantly (p EpF was the most powerful determinant of LVDD (odds ratio = 2.41, 95% confidence interval = 1.43-4.08, p EpF thickness also correlated significantly with the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e'; r = 0.27, p EpF thickness is significantly independently associated with LVDD in patients undergoing PD and may be involved in its pathogenesis.

  13. LDL Receptor-Related Protein-1 (LRP1 Regulates Cholesterol Accumulation in Macrophages.

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    Anna P Lillis

    Full Text Available Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cell formation are incompletely understood. To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cell formation, but the in vivo contribution of the LDL receptor-related protein 1 (LRP1 to this process is not known [corrected]. To investigate the role of LRP1 in cholesterol accumulation in macrophages, we generated mice with a selective deletion of LRP1 in macrophages on an LDL receptor (LDLR-deficient background (macLRP1-/-. After feeding mice a high fat diet for 11 weeks, peritoneal macrophages isolated from Lrp+/+ mice contained significantly higher levels of total cholesterol than those from macLRP1-/- mice. Further analysis revealed that this was due to increased levels of cholesterol esters. Interestingly, macLRP1-/- mice displayed elevated plasma cholesterol and triglyceride levels resulting from accumulation of large, triglyceride-rich lipoprotein particles in the circulation. This increase did not result from an increase in hepatic VLDL biosynthesis, but rather results from a defect in catabolism of triglyceride-rich lipoprotein particles in macLRP1-/- mice. These studies reveal an important in vivo contribution of macrophage LRP1 to cholesterol homeostasis.

  14. Salt stress encourages proline accumulation by regulating proline biosynthesis and degradation in Jerusalem artichoke plantlets.

    Science.gov (United States)

    Huang, Zengrong; Zhao, Long; Chen, Dandan; Liang, Mingxiang; Liu, Zhaopu; Shao, Hongbo; Long, Xiaohua

    2013-01-01

    Proline accumulation is an important mechanism for osmotic regulation under salt stress. In this study, we evaluated proline accumulation profiles in roots, stems and leaves of Jerusalem artichoke (Helianthus tuberosus L.) plantlets under NaCl stress. We also examined HtP5CS, HtOAT and HtPDH enzyme activities and gene expression patterns of putative HtP5CS1, HtP5CS2, HtOAT, HtPDH1, and HtPDH2 genes. The objective of our study was to characterize the proline regulation mechanisms of Jerusalem artichoke, a moderately salt tolerant species, under NaCl stress. Jerusalem artichoke plantlets were observed to accumulate proline in roots, stems and leaves during salt stress. HtP5CS enzyme activities were increased under NaCl stress, while HtOAT and HtPDH activities generally repressed. Transcript levels of HtP5CS2 increased while transcript levels of HtOAT, HtPDH1 and HtPDH2 generally decreased in response to NaCl stress. Our results supports that for Jerusalem artichoke, proline synthesis under salt stress is mainly through the Glu pathway, and HtP5CS2 is predominant in this process while HtOAT plays a less important role. Both HtPDH genes may function in proline degradation.

  15. Salt stress encourages proline accumulation by regulating proline biosynthesis and degradation in Jerusalem artichoke plantlets.

    Directory of Open Access Journals (Sweden)

    Zengrong Huang

    Full Text Available Proline accumulation is an important mechanism for osmotic regulation under salt stress. In this study, we evaluated proline accumulation profiles in roots, stems and leaves of Jerusalem artichoke (Helianthus tuberosus L. plantlets under NaCl stress. We also examined HtP5CS, HtOAT and HtPDH enzyme activities and gene expression patterns of putative HtP5CS1, HtP5CS2, HtOAT, HtPDH1, and HtPDH2 genes. The objective of our study was to characterize the proline regulation mechanisms of Jerusalem artichoke, a moderately salt tolerant species, under NaCl stress. Jerusalem artichoke plantlets were observed to accumulate proline in roots, stems and leaves during salt stress. HtP5CS enzyme activities were increased under NaCl stress, while HtOAT and HtPDH activities generally repressed. Transcript levels of HtP5CS2 increased while transcript levels of HtOAT, HtPDH1 and HtPDH2 generally decreased in response to NaCl stress. Our results supports that for Jerusalem artichoke, proline synthesis under salt stress is mainly through the Glu pathway, and HtP5CS2 is predominant in this process while HtOAT plays a less important role. Both HtPDH genes may function in proline degradation.

  16. The Fat-Dachsous signaling pathway regulates growth of horns in Trypoxylus dichotomus, but does not affect horn allometry.

    Science.gov (United States)

    Hust, James; Lavine, Mark D; Worthington, Amy M; Zinna, Robert; Gotoh, Hiroki; Niimi, T; Lavine, Laura

    Males of the Asian rhinoceros beetle, Trypoxylus dichotomus, possess exaggerated head and thoracic horns that scale dramatically out of proportion to body size. While studies of insulin signaling suggest that this pathway regulates nutrition-dependent growth including exaggerated horns, what regulates disproportionate growth has yet to be identified. The Fat signaling pathway is a potential candidate for regulating disproportionate growth of sexually-selected traits, a hypothesis we advanced in a previous paper (Gotoh et al., 2015). To investigate the role of Fat signaling in the growth and scaling of the sexually dimorphic, condition-dependent traits of the in the Asian rhinoceros beetle T. dichotomus, we used RNA interference to knock down expression of fat and its co-receptor dachsous. Knockdown of fat, and to a lesser degree dachsous, caused shortening and widening of appendages, including the head and thoracic horns. However, scaling of horns to body size was not affected. Our results show that Fat signaling regulates horn growth in T. dichotomus as it does in appendage growth in other insects. However, we provide evidence that Fat signaling does not mediate the disproportionate, positive allometric growth of horns in T. dichotomus. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Associations among eating regulation and body mass index, weight, and body fat in college students: the moderating role of gender.

    Science.gov (United States)

    Gropper, Sareen S; Arsiwalla, Dilbur D; Lord, Denali C; Huggins, Kevin W; Simmons, Karla P; Ulrich, Pamela V

    2014-04-01

    This study investigated associations between eating regulation behaviors and body mass index (BMI), weight, and percent body fat in male and female students over the first two years of college. Subjects included 328 college students (215 females and 113 males). Height and weight (via standard techniques), body composition (via bioelectrical impedance analysis), and eating regulation behaviors (using the Regulation of Eating Behavior Scale) were conducted two to three times during both the freshman and sophomore years. Significant associations between eating regulation and BMI, weight, and/or percent body fat were shown mostly in females. In females, higher BMI, weight, and/or percent body fat at the end of the second year of college were found in those with low levels of autonomous, intrinsic motivation, and identified regulation, and high levels of amotivation, while lower BMI, weight, and/or percent body fat were associated with high levels of autonomous, intrinsic motivation, and identified regulation, and low levels of amotivation. The findings that specific eating behaviors in females during the first two years of college influence BMI, weight, and/or percent body fat may be useful for inclusion in university programs focused on college student health to help decrease the risk of obesity and disordered eating/eating disorders in female college students. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Visceral fat accumulation in relation to sex hormones in obese men and women undergoing weight loss therapy

    NARCIS (Netherlands)

    Leenen, R; van der Kooy, K; Seidell, J C; Deurenberg, P.; Koppeschaar, H.P.

    In 70 healthy obese subjects (37 men and 33 premenopausal women; aged 27-51 yr; body mass index, 28-38 kg/m2), associations between the initial amount of visceral fat and sex hormone levels were studied as well as between changes that occurred in response to a 4.2 mJ/day deficit diet for 13 weeks.

  19. The effects of Bee Venom and Sweet Bee Venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation

    Directory of Open Access Journals (Sweden)

    Min-Ki Kim

    2007-12-01

    Full Text Available Objectives : The purpose of this study was to investigate the effects of Bee Venom and Sweet Bee Venom to the primary cultured preadipocyte, adipocytes, and localized fat tissue. Methods : Decreased preadipocyte proliferation and decreased lipogenesis are mechanisms to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures using Sprague-Dawley Rats and treated with 0.01-1mg/㎖ Bee Venom and Sweet Bee Venom. And porcine skin including fat tissue after treated Bee Venom and Sweet Bee Venom according to the dosage dependent variation are investigated the histologic changes after injection of these Pharmacopuncture. Result : Following results were obtained from the preadipocyte proliferation and lipolysis of adipocyte and histologic investigation of fat tissue. 1. Bee Venom and Sweet Bee Venom showed the effect of decreased preadipocyte proliferation depend on concentration. 2. Bee Venom and Sweet Bee Venom showed the effect of decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH significantly. 3. Bee Venom was not showed the effect of lipolysis, but Sweet Bee Venom was increased in low dosage and decreased in high dosage. 4. Investigated the histologic changes in porcine fat tissue after treated Bee Venom and Sweet Bee Venom, we knew that these Pharmacopuncture was activated nonspecific lysis of cell membranes depend on concentration. Conclusion : These results suggest that Bee Venom and Sweet Bee Venom efficiently induces decreased proliferation of preadipocyte and lipolysis in adipose tissue

  20. Co-culture with infrapatellar fat pad differentially stimulates proteoglycan synthesis and accumulation in cartilage and meniscus tissues.

    Science.gov (United States)

    Nishimuta, James F; Bendernagel, Monica F; Levenston, Marc E

    2017-09-01

    Although osteoarthritis is widely viewed as a disease of the whole joint, relatively few studies have focused on interactions among joint tissues in joint homeostasis and degeneration. In particular, few studies have examined the effects of the infrapatellar fat pad (IFP) on cartilaginous tissues. The aim of this study was to test the hypothesis that co-culture with healthy IFP would induce degradation of cartilage and meniscus tissues. Bovine articular cartilage, meniscus, and IFP were cultured isolated or as cartilage-fat or meniscus-fat co-cultures for up to 14 days. Conditioned media were assayed for sulfated glycosaminoglycan (sGAG) content, nitrite content, and matrix metalloproteinase (MMP) activity, and explants were assayed for sGAG and DNA contents. Co-cultures exhibited increased cumulative sGAG release and sGAG release rates for both cartilage and meniscus, and the cartilage (but not meniscus) exhibited a substantial synergistic effect of co-culture (sGAG release in co-culture was significantly greater than the summed release from isolated cartilage and fat). Fat co-culture did not significantly alter the sGAG content of either cartilage or meniscus explants, indicating that IFP co-culture stimulated net sGAG production by cartilage. Nitrite release was increased relative to isolated tissue controls in co-cultured meniscus, but not the cartilage, with no synergistic effect of co-culture. Interestingly, MMP-2 production was decreased by co-culture for both cartilage and meniscus. This study demonstrates that healthy IFP may modulate joint homeostasis by stimulating sGAG production in cartilage. Counter to our hypothesis, healthy IFP did not promote degradation of either cartilage or meniscus tissues.

  1. SET oncoprotein accumulation regulates transcription through DNA demethylation and histone hypoacetylation.

    Science.gov (United States)

    Almeida, Luciana O; Neto, Marinaldo P C; Sousa, Lucas O; Tannous, Maryna A; Curti, Carlos; Leopoldino, Andreia M

    2017-04-18

    Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation. DNA methylation profile of 24 tumour suppressors evidenced that SET accumulation decreased DNA methylation in association with loss of 5-methylcytidine, formation of 5-hydroxymethylcytosine and increased TET1 levels, indicating an active DNA demethylation mechanism. However, the expression of some suppressor genes was lowered in cells with high SET levels, suggesting that loss of methylation is not the main mechanism modulating gene expression. SET accumulation also downregulated the expression of 32 genes of a panel of 84 transcription factors, and SET directly interacted with chromatin at the promoter of the downregulated genes, decreasing histone acetylation. Gene expression analysis after cell treatment with 5-aza-2'-deoxycytidine (5-AZA) and Trichostatin A (TSA) revealed that histone acetylation reversed transcription repression promoted by SET. These results suggest a new function for SET in the regulation of chromatin dynamics. In addition, TSA diminished both SET protein levels and SET capability to bind to gene promoter, suggesting that administration of epigenetic modifier agents could be efficient to reverse SET phenotype in cancer.

  2. Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats.

    Science.gov (United States)

    Ríos-Lugo, María J; Jiménez-Ortega, Vanesa; Cano-Barquilla, Pilar; Mateos, Pilar Fernández; Spinedi, Eduardo J; Cardinali, Daniel P; Esquifino, Ana I

    2015-03-01

    Previous studies indicate that the administration of melatonin caused body weight and abdominal visceral fat reductions in rodent models of hyperadiposity. The objective of the present study performed in high-fat fed rats was to evaluate the activity of melatonin on gene expression of some medial basal hypothalamus (MBH) signals involved in feeding behavior regulation, including neuropeptide Y (NPY), proopiomelanocortin (POMC), prolactin-releasing peptide (PrRP), leptin- and insulin-receptors (R) and insulin-R substrate (IRS)-1 and -2. Blood levels of leptin and adiponectin were also measured. Adult Wistar male rats were divided into four groups (n=16 per group): (i) control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet+melatonin; (iv) control diet+melatonin. Rats had free access to high-fat or control chow and one of the following drinking solutions: (a) tap water; (b) 25 μg/mL of melatonin. After 10 weeks, the high-fat fed rats showed augmented MBH mRNA levels of NPY, leptin-R, PrRP, insulin-R, IRS-1 and IRS-2. The concomitant administration of melatonin counteracted this increase. Feeding of rats with a high-fat diet augmented expression of the MBH POMC gene through an effect insensitive to melatonin treatment. The augmented levels of circulating leptin and adiponectin seen in high-fat fed rats were counteracted by melatonin as was the augmented body weight: melatonin significantly attenuated a body weight increase in high-fat fed rats without affecting chow or water consumption. Melatonin augmented plasma leptin and adiponectin in control rats. The results indicate that an effect on gene expression of feeding behavior signals at the central nervous system (CNS) may complement a peripheral rise of the energy expenditure produced by melatonin to decrease body weight in high-fat fed rats.

  3. Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

    Directory of Open Access Journals (Sweden)

    Ori Nov

    Full Text Available The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers, Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4 that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin

  4. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [Scripps Research Inst., La Jolla, CA (United States); Hazen, Samuel [Scripps Research Inst., San Diego, CA (United States); Mullet, John [Texas A & M Univ., College Station, TX (United States)

    2017-11-22

    Critical to the development of renewable energy sources from biofuels is the improvement of biomass from energy feedstocks, such as sorghum and maize. The specific goals of this project include 1) characterize the growth and gene expression patterns under diurnal and circadian conditions, 2) select transcription factors associated with growth and build a cis-regulatory network in yeast, and 3) perturb these transcription factors in planta using transgenic Brachypodium and sorghum, and characterize the phenotypic outcomes as they relate to biomass accumulation. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield.

  5. MiR130b-Regulation of PPARγ Coactivator- 1α Suppresses Fat Metabolism in Goat Mammary Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Zhi Chen

    Full Text Available Fat metabolism is a complicated process regulated by a series of factors. microRNAs (miRNAs are a class of negative regulator of proteins and play crucial roles in many biological processes; including fat metabolism. Although there have been some researches indicating that miRNAs could influence the milk fat metabolism through targeting some factors, little is known about the effect of miRNAs on goat milk fat metabolism. Here we utilized an improved miRNA detection assay, S-Poly-(T, to profile the expression of miRNAs in the goat mammary gland in different periods, and found that miR-130b was abundantly and differentially expressed in goat mammary gland. Additionally, overexpressing miR-130b impaired adipogenesis while inhibiting miR-130b enhanced adipogenesis in goat mammary epithelial cells. Utilizing 3'-UTR assay and Western Blot analusis, the protein peroxisome proliferator-activated receptor coactivator-1α (PGC1α, a major regulator of fat metabolism, was demonstrated to be a potential target of miR-130b. Interestingly, miR-130b potently repressed PGC1α expression by targeting both the PGC1α mRNA coding and 3' untranslated regions. These findings have some insight of miR-130b in mediating adipocyte differentiation by repressing PGC1α expression and this contributes to further understanding about the functional significance of miRNAs in milk fat synthesis.

  6. Buddleja officinalis Maximowicz Extract Inhibits Lipid Accumulation on Adipocyte Differentiation in 3T3-L1 Cells and High-Fat Mice

    Directory of Open Access Journals (Sweden)

    Jin-Kyu Kim

    2012-07-01

    Full Text Available Obesity is a global health problem. It is also known to be a risk factor for the development of metabolic disorders, type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we elucidated that Buddleja officinalis Maximowicz extract significantly inhibited lipid accumulation during 3T3-L1 adipocyte differentiation. Furthermore, Buddleja officinalis Maximowicz extract reduced the body weight gain induced through feeding a high-fat diet to C57BL/6 mice. The treatment of Buddleja officinalis Maximowicz extract significantly reduced the adipose tissue weight to 2.7/100 g of body weight in high-fat mice. When their adipose tissue morphology was investigated for histochemical staining, the distribution of cell size in the high-fat diet groups was hypertrophied compared with those from Buddleja officinalis Maximowicz extract-treated mice. In addition, in Buddleja officinalis Maximowicz extract-treated mice, a significant reduction of serum triglyceride and T-cholesterol was observed at to 21% and 17%, respectively. The discovery of bioactive compounds from diet or dietary supplementation is one of possible ways to control obesity and to prevent or reduce the risks of various obesity-related diseases. These results support that Buddleja officinalis Maximowicz extract is expected to create the therapeutic interest with respect to the treatment of obesity.

  7. Buddleja officinalis Maximowicz extract inhibits lipid accumulation on adipocyte differentiation in 3T3-L1 cells and high-fat mice.

    Science.gov (United States)

    Roh, Changhyun; Park, Min-Kyoung; Shin, Hee-June; Jung, Uhee; Kim, Jin-Kyu

    2012-07-23

    Obesity is a global health problem. It is also known to be a risk factor for the development of metabolic disorders, type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we elucidated that Buddleja officinalis Maximowicz extract significantly inhibited lipid accumulation during 3T3-L1 adipocyte differentiation. Furthermore, Buddleja officinalis Maximowicz extract reduced the body weight gain induced through feeding a high-fat diet to C57BL/6 mice. The treatment of Buddleja officinalis Maximowicz extract significantly reduced the adipose tissue weight to 2.7/100 g of body weight in high-fat mice. When their adipose tissue morphology was investigated for histochemical staining, the distribution of cell size in the high-fat diet groups was hypertrophied compared with those from Buddleja officinalis Maximowicz extract-treated mice. In addition, in Buddleja officinalis Maximowicz extract-treated mice, a significant reduction of serum triglyceride and T-cholesterol was observed at to 21% and 17%, respectively. The discovery of bioactive compounds from diet or dietary supplementation is one of possible ways to control obesity and to prevent or reduce the risks of various obesity-related diseases. These results support that Buddleja officinalis Maximowicz extract is expected to create the therapeutic interest with respect to the treatment of obesity.

  8. Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity

    Directory of Open Access Journals (Sweden)

    T.S. de Melo

    Full Text Available Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20–25 g (n=6–8 per group were fed a normal diet (ND or HFD, treated orally or not with either FA (10 mg/kg or sibutramine (10 mg/kg for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCH-1 were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05 decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05 reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05 inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.

  9. Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High-Fructose Diet

    Directory of Open Access Journals (Sweden)

    Da-Wei Huang

    2018-01-01

    Full Text Available This study investigated the ameliorative effect of gallic acid (GA on hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high-fructose diet (HFD-induced diabetic rats. The previous results showed that orally administered GA (30 mg/kg body weight for four weeks significantly reduced the levels of plasma glucose and triglyceride (TG in HFD rats. GA also markedly decreased the perirenal adipose tissues weight of HFD rats in present study (p < 0.05. Western blot assay indicated that GA restored expression of insulin signaling-related proteins, such as insulin receptor (IR, protein kinase C-zeta (PKC-ζ, and glucose transporter-4 (GLUT4 in the perirenal adipose tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related proteins, such as phosphofructokinase (PFK and pyruvate kinase (PK, and increased the expression of lipolysis-related proteins, such as adipose triglyceride lipase (ATGL, which is involved in lipolysis in the perirenal adipose tissues of HFD rats. This study revealed that GA may alleviate hypertriglyceridemia and fat accumulation through enhancing glycolysis and lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also suggest the potential of GA in preventing the progression of diabetes mellitus (DM complications.

  10. Persistent organic pollutants in fat of three species of Pacific pelagic longline caught sea turtles: Accumulation in relation to ingested plastic marine debris

    Science.gov (United States)

    Clukey, Katharine; Lepczyk, Christopher A.; Balazs, George H.; Work, Thierry M.; Li, Qing X.; Bachman, Melanie J.; Lynch, Jennifer M.

    2017-01-01

    In addition to eating contaminated prey, sea turtles may be exposed to persistent organic pollutants (POPs) from ingesting plastic debris that has absorbed these chemicals. Given the limited knowledge about POPs in pelagic sea turtles and how plastic ingestion influences POP exposure, our objectives were to: 1) provide baseline contaminant levels of three species of pelagic Pacific sea turtles; and 2) assess trends of contaminant levels in relation to species, sex, length, body condition and capture location. In addition, we hypothesized that if ingesting plastic is a significant source of POP exposure, then the amount of ingested plastic may be correlated to POP concentrations accumulated in fat. To address our objectives we compared POP concentrations in fat samples to previously described amounts of ingested plastic from the same turtles. Fat samples from 25 Pacific pelagic sea turtles [2 loggerhead (Caretta caretta), 6 green (Chelonia mydas) and 17 olive ridley (Lepidochelys olivacea) turtles] were analyzed for 81 polychlorinated biphenyls (PCBs), 20 organochlorine pesticides, and 35 brominated flame-retardants. The olive ridley and loggerhead turtles had higher ΣDDTs (dichlorodiphenyltrichloroethane and metabolites) than ΣPCBs, at a ratio similar to biota measured in the South China Sea and southern California. Green turtles had a ratio close to 1:1. These pelagic turtles had lower POP levels than previously reported in nearshore turtles. POP concentrations were unrelated to the amounts of ingested plastic in olive ridleys, suggesting that their exposure to POPs is mainly through prey. In green turtles, concentrations of ΣPCBs were positively correlated with the number of plastic pieces ingested, but these findings were confounded by covariance with body condition index (BCI). Green turtles with a higher BCI had eaten more plastic and also had higher POPs. Taken together, our findings suggest that sea turtles accumulate most POPs through their prey rather

  11. The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

    Science.gov (United States)

    Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

    2018-01-01

    Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins.

    Science.gov (United States)

    Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Kim, Ji-Eun; Kim, Seung-Chul; Jeung, Eui-Bae; Lee, Geun-Shik; Hwang, Dae-Youn; An, Beum-Soo

    2015-07-01

    Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Phenylpropanoids accumulation in eggplant fruit: characterization of biosynthetic genes and regulation by a MYB transcription factor

    Directory of Open Access Journals (Sweden)

    Teresa eDocimo

    2016-01-01

    Full Text Available Phenylpropanoids are major secondary metabolites in eggplant (Solanum melongena fruits. Chlorogenic acid (CGA accounts for 70 to 90% of total phenolics in flesh tissues, while anthocyanins are mainly present in the fruit skin. As a contribution to the understanding of the peculiar accumulation of these health-promoting metabolites in eggplant, we report on metabolite abundance, regulation of CGA and anthocyanin biosynthesis, and characterization of candidate CGA biosynthetic genes in S. melongena.Higher contents of CGA, Delphinidin 3-rutinoside and rutin were found in eggplant fruits compared to other tissues, associated to an elevated transcript abundance of structural genes such as PAL, HQT, DFR and ANS, suggesting that active in situ biosynthesis contributes to anthocyanin and CGA accumulation in fruit tissues. Putative orthologs of the two CGA biosynthetic genes PAL and HQT, as well as a variant of a MYB1 transcription factor showing identity with group 6 MYBs, were isolated from an Occidental S. melongena traditional variety and demonstrated to differ from published sequences from Asiatic varieties.In silico analysis of the isolated SmPAL1, SmHQT1, SmANS, and SmMyb1 promoters revealed the presence of several Myb regulatory elements for the biosynthetic genes and unique elements for the TF, suggesting its involvement in other physiological roles beside phenylpropanoid biosynthesis regulation.Transient overexpression in Nicotiana benthamiana leaves of SmMyb1 and of a C-terminal SmMyb1 truncated form (SmMyb1Δ9 resulted in anthocyanin accumulation only of SmMyb1 agro-infiltrated leaves. A yeast two-hybrid assay confirmed the interaction of both SmMyb1 and SmMyb1Δ9 with an anthocyanin-related potato bHLH1 TF. Interestingly, a doubled amount of CGA was detected in both SmMyb1 and SmMyb1Δ9 agro-infiltrated leaves, thus suggesting that the N-terminal region of SmMyb1 is sufficient to activate its synthesis. These data suggest that a deletion of

  14. Mitochondrial DNA Copy Number in Peripheral Blood Is Independently Associated with Visceral Fat Accumulation in Healthy Young Adults

    Directory of Open Access Journals (Sweden)

    Jee-Yon Lee

    2014-01-01

    Full Text Available Aims. Visceral obesity is associated with an increased risk of cardiometabolic diseases and it is important to identify the underlying mechanisms. There is growing evidence that mitochondrial dysfunction is associated with metabolic disturbances related to visceral obesity. In addition, maintaining mitochondrial DNA (mtDNA copy number is important for preserving mitochondrial function. Therefore, we investigated the relationship between mtDNA copy number and visceral fat in healthy young adults. Methods. A total of 94 healthy young subjects were studied. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. mtDNA copy number was measured in peripheral leukocytes using real-time polymerase chain reaction (PCR methods. Results. The mtDNA copy number correlated with BMI (r=-0.22, P=0.04, waist circumference (r=-0.23, P=0.03, visceral fat area (r=-0.28, P=-0.01, HDL-cholesterol levels (r=0.25, P=0.02, and hs-CRP (r=0.32, P=0.02 after adjusting for age and sex. Both stepwise and nonstepwise multiple regression analyses confirmed that visceral fat area was independently associated with mtDNA copy number (β=-0.33, P<0.01, β=0.32, and P=0.03, resp.. Conclusions. An independent association between mtDNA content and visceral adiposity was identified. These data suggest that mtDNA copy number is a potential predictive marker for metabolic disturbances. Further studies are required to understand the causality and clinical significance of our findings.

  15. Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B Golden Syrian hamsters.

    Science.gov (United States)

    Dillard, Alice; Matthan, Nirupa R; Spartano, Nicole L; Butkowski, Ann E; Lichtenstein, Alice H

    2013-12-01

    Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.

  16. Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years.

    Science.gov (United States)

    Kocarnik, Beverly M; Boyko, Edward J; Matsumoto, Alvin M; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Leonetti, Donna L; Page, Stephanie T

    The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. This is a longitudinal observational study in community-dwelling Japanese-American men (n=215, mean age 52 years, BMI 25.4kg/m 2 ). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r=-0.05 for both time points, p=0.45 and p=0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p=0.52 and p=0.55, respectively). Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. Copyright © 2015 Asia Oceania Association for the Study of Obesity. All rights reserved.

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-22

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

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

    International Nuclear Information System (INIS)

    Kim, Kyung Jin; Lee, Myoung-Su; Jo, Keunae; Hwang, Jae-Kwan

    2011-01-01

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

  20. The Csr System Regulates Escherichia coli Fitness by Controlling Glycogen Accumulation and Energy Levels.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Cinquemani, Eugenio; Portais, Jean-Charles; Enjalbert, Brice; Cocaign-Bousquet, Muriel

    2017-10-31

    In the bacterium Escherichia coli , the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences E. coli fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation. IMPORTANCE Glycogen is a polysaccharide and the main storage form of glucose from bacteria such as Escherichia coli to yeasts and mammals. Although its function as a sugar reserve in mammals is well documented, the role of glycogen in bacteria is not as clear. By studying the role of posttranscriptional regulation during metabolic adaptation, for the first time, we demonstrate the role of sugar reserve played by glycogen in E. coli Indeed, glycogen not only makes it possible to maintain sufficient energy during metabolic transitions but is also the key component in the capacity of cells to resume growth. Since the essential posttranscriptional regulatory system Csr is a major regulator of glycogen accumulation, this work also sheds light on the central role of posttranscriptional regulation in metabolic adaptation. Copyright © 2017 Morin et al.

  1. The lipid accumulation product as a useful index for identifying abnormal glucose regulation in young Korean women.

    Science.gov (United States)

    Oh, J-Y; Sung, Y-A; Lee, H J

    2013-04-01

    The lipid accumulation product, a combination of waist circumference and triglycerides concentration, has been suggested as a better marker for abnormal glucose regulation than BMI. We aimed to compare the lipid accumulation product and BMI as useful markers for abnormal glucose regulation in young Korean women. The lipid accumulation product was calculated using the formula [waist circumference (cm) - 58] × triglycerides (mmol/l). Glucose tolerance status was determined using a 75-g oral glucose tolerance test in 2810 Korean women aged 18-39 years from the general population. The prevalence of abnormal glucose regulation was 6.8% (isolated impaired fasting glucose 1.8%, isolated impaired glucose tolerance 4.0%; impaired fasting glucose + impaired glucose tolerance 0.4% and diabetes mellitus 0.6%). According to the quintile distributions of the lipid accumulation product and BMI, women with a lipid accumulation product quintile greater than their BMI quintile exhibited significantly greater areas under the curve and higher levels of 2-h post-load glucose, insulin, homeostasis model analysis of insulin resistance and lipid profiles than did women with a BMI quintile greater than their lipid accumulation product quintile. Multiple logistic regression revealed that the lipid accumulation product exhibited a higher odds ratio for abnormal glucose regulation than did BMI after adjusting for age, systolic blood pressure, HDL cholesterol, previous history of gestational diabetes and family history of diabetes (odds ratios 3.5 and 2.6 of the highest vs. the lowest quintiles of lipid accumulation product and BMI, respectively). The lipid accumulation product could be useful for identifying the young Korean women with abnormal glucose regulation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  2. The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation.

    Science.gov (United States)

    Koda, Michiko; Kitamura, Itsuko; Okura, Tomohiro; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

    2016-01-01

    Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c) levels of 877 males were also assessed. In the VFA smoking habits and VFA was associated with the subjects' TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA. Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA.

  3. Offspring from rat mothers fed a high-fat/high-sucrose diet during gestation and lactation accumulate free fatty acids in the liver when exposed to high fat diet as adults

    DEFF Research Database (Denmark)

    Hellgren, Lars; Ingvorsen, Camilla

    Introduction: Maternal diet during gestation and lactation has been implicated as a factor that modifies the risk of developing metabolic diseases later in life. Hepatic lipid accumulation is strongly linked to development of metabolic diseases. Free fatty acids induce ER stress, mitochondrial...... in adult life. In this poster, we report data on hepatic lipid content. Methods: Rat dams were fed a 60 E% fat diet and given 15% sucrose (HFHS) in the drinking water or chow and pure water (C) six weeks before mating as well as during gestation and lactation. After birth, male pups was cross......-fostered by the dams, so that half of the pups born by HFHS mothers was lactated by C dams and vice versa, generating four groups; CC, CH, HC and HH (first letter maternal diet during pregnancy and the second diet during lactation). At weaning all pups were transferred to chow-diet and kept on this diet until the age...

  4. Food intake regulation in children. Fat and sugar substitutes and intake.

    Science.gov (United States)

    Birch, L L; Fisher, J O

    1997-05-23

    intake, but because these adjustments in energy intake are not macronutrient specific, changes in the overall macronutrient composition of children's diets can be obtained. There does not appear to be anything unique or special about the effects of macronutrient substitutes on children's intake; their effects are similar to those produced by other manipulations of macronutrient and energy content accomplished without macronutrient substitutes (e.g., augmenting foods with fat or carbohydrate to produce macronutrient differences). The research also indicates that under conditions that minimize adult attempts to control how much and what children eat, children can adjust their food and energy intake in response to the alterations of macronutrient and energy content of foods. Whether or not young children adjust food intake to compensate for energy-density changes depends upon their opportunity to control their own food intake as opposed to having their intake controlled by others. Young children's ability to adjust intake in response to alterations in the energy density of foods can be readily disrupted by the imposition of controlling child-feeding practices that attempt to regulate what and how much children eat. We believe that early experiences, including child-feeding practices imposed by parents, are major factors contributing to the etiology of individual differences and gender differences in the behavioral controls of food intake that can occur in response to the energy content of foods. The extent to which children respond to energy density of the diet has major implications for the effects of fat and sugar substitutes on children's intake. If children who are responsive to energy density consume substantial amounts of foods containing macronutrient substitutes, they should show some adjustments in intake to compensate for reduced energy, so that the impact of macronutrient substitutes on energy intake may be relatively small. However, changes in macronutrient com

  5. Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Roepstorff, Carsten; Halberg, Nils; Hillig, Thore

    2005-01-01

    Intracellular mechanisms regulating fat oxidation were investigated in human skeletal muscle during exercise. Eight young, healthy, moderately trained men performed bicycle exercise (60 min, 65% peak O2 consumption) on two occasions, where they ingested either 1) a high-carbohydrate diet (H-CHO) ...

  6. Hypothalamic PGC-1α Protects Against High-Fat Diet Exposure by Regulating ERα

    Directory of Open Access Journals (Sweden)

    Eugenia Morselli

    2014-10-01

    Full Text Available High-fat diets (HFDs lead to obesity and inflammation in the central nervous system (CNS. Estrogens and estrogen receptor α (ERα protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

  7. Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα.

    Science.gov (United States)

    Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P; Li, Dan L; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F; Tschöp, Matthias H; Clegg, Deborah J

    2014-10-23

    High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor α (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

  8. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  9. The Mammalian “Obesogen” Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G.; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C. Marisa R.; Teixeira, Catarina; Castro, L. Filipe C.; Santos, Miguel M.

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound. PMID:26633012

  10. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C Marisa R; Teixeira, Catarina; Castro, L Filipe C; Santos, Miguel M

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  11. Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

    Science.gov (United States)

    Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

    2011-05-01

    Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

  12. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [Univ. of Southern California, Los Angeles, CA (United States)

    2017-10-20

    Objectives: Several breakthroughs have been recently made in our understanding of plant growth and biomass accumulation. It was found that plant growth is rhythmically controlled throughout the day by the circadian clock through a complex interplay of light and phytohormone signaling pathways. While plants such as the C4 energy crop sorghum (Sorghum bicolor (L.) Moench) and possibly the C3 grass Brachypodium distachyon also exhibit daily rhythms in growth rate, the molecular details of its regulation remain to be explored. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield. Here we propose to devise a systems approach to identify, in parallel, regulatory hubs associated with rhythmic growth in C3 and C4 plants. We propose to use rhythmicity in daily growth patterns to drive the discovery of regulatory network modules controlling biomass accumulation. Description: The project is divided in three main parts: 1) Performing time-lapse imaging and growth measurement in B. distachyon and S. bicolor to determine growth rate dynamic during the day/night cycle. Identifying growth-associated genes whose expression patterns follow the observed growth dynamics using deep sequencing technology, 2) identifying regulators of these genes by screening for DNA-binding proteins interacting with the growth-associated gene promoters identified in Aim 1. Screens will be performed using a validated yeast-one hybrid strategy paired with a specifically designed B. distachyon and S. bicolor transcription factor libraries (1000 clones each), and 3) Selecting 50 potential growth regulators from the screen for downstream characterization. The selection will be made by using a sytems biology approach by calculating the connectivity between growth rate, rhythmic gene expression profiles and TF expression profile and determine which TF is likely part of a hub

  13. Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation.

    Science.gov (United States)

    Axelsen, Lene N; Lademann, Jacob B; Petersen, Jørgen S; Holstein-Rathlou, Niels-Henrik; Ploug, Thorkil; Prats, Clara; Pedersen, Henrik D; Kjølbye, Anne Louise

    2010-06-01

    Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure volume measurements, and intramyocardial lipid accumulation was analyzed by confocal microscopy. Cardiac AMP-activated kinase (AMPK) and hepatic phosphoenolpyruvate carboxykinase (PEPCK) levels were measured by Western blotting. Finally, an ischemia-reperfusion study was performed after 56 wk of feeding. FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed significant intramyocardial lipid accumulation, and cardiac hypertrophy became pronounced between 24 and 36 wk of feeding. FFFRs showed no signs of cardiac dysfunction during unstressed conditions, but their hearts were much more vulnerable to ischemia-reperfusion and had a decreased level of phosphorylated AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications.

  14. Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice

    Directory of Open Access Journals (Sweden)

    Yuzuru Iizuka

    Full Text Available Pioglitazone, a thiazolidinedione (TZD, is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO, safflower oil/low-dose pioglitazone (S/PL, and safflower oil/high-dose pioglitazone (S/PH diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt pioglitazone, respectively. In fish oil (FO, fish oil/low-dose pioglitazone (F/PL, and fish oil/high-dose pioglitazone (F/PH diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups; however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis. Keywords: Fish oil, Pioglitazone, Adverse effect

  15. Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats.

    Science.gov (United States)

    Le Foll, Christelle; Dunn-Meynell, Ambrose A; Levin, Barry E

    2015-02-01

    Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing CD36 shRNA (AAV CD36 shRNA) leads to redistribution of adipose stores and insulin resistance in outbred rats. This study assessed the requirement of VMH CD36-mediated FA sensing for the regulation of energy and glucose homeostasis in postnatal day 5 (P5) and P21 selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats using VMH AAV CD36 shRNA injections. P5 CD36 depletion altered VMH neuronal FA sensing predominantly in DIO rats. After 10 wk on a 45% fat diet, DIO rats injected with VMH AAV CD36 shRNA at P21 ate more and gained more weight than DIO AAV controls, while DR AAV CD36 shRNA-injected rats gained less weight than DR AAV controls. VMH CD36 depletion increased inguinal fat pad weights and leptin levels in DIO and DR rats. Although DR AAV CD36 shRNA-injected rats became as obese as DIO AAV controls, only DIO control and CD36 depleted rats became insulin-resistant on a 45% fat diet. VMH CD36 depletion stunted linear growth in DIO and DR rats. DIO rats injected with AAV CD36 shRNA at P5 had increased fat mass, mostly due to a 45% increase in subcutaneous fat. They were also insulin-resistant with an associated 71% increase of liver triglycerides. These results demonstrate that VMH CD36-mediated FA sensing is a critical factor in the regulation of energy and glucose homeostasis and fat deposition in DIO and DR rats.

  16. CNS β3-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight.

    Science.gov (United States)

    Richard, Jennifer E; López-Ferreras, Lorena; Chanclón, Belén; Eerola, Kim; Micallef, Peter; Skibicka, Karolina P; Wernstedt Asterholm, Ingrid

    2017-09-01

    Pharmacological β 3 -adrenergic receptor (β 3 AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as "browning", and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of β 3 AR agonists is mediated solely through activation of β 3 ARs in adipose tissue. However, β 3 ARs are also found in the brain, in areas such as the brain stem and the hypothalamus, which provide multisynaptic innervation to brown and white adipose depots. Thus, contrary to the current adipocentric view, the central nervous system (CNS) may also have the ability to regulate energy balance and metabolism through actions on central β 3 ARs. Therefore, this study aimed to elucidate whether CNS β 3 ARs can regulate browning of WAT and other aspects of metabolic regulation, such as food intake control and insulin release. We found that acute central injection of β 3 AR agonist potently reduced food intake, body weight, and increased hypothalamic neuronal activity in rats. Acute central β 3 AR stimulation was also accompanied by a transient increase in circulating insulin levels. Moreover, subchronic central β 3 AR agonist treatment led to a browning response in both inguinal (IWAT) and gonadal WAT (GWAT), along with reduced GWAT and increased BAT mass. In high-fat, high-sugar-fed rats, subchronic central β 3 AR stimulation reduced body weight, chow, lard, and sucrose water intake, in addition to increasing browning of IWAT and GWAT. Collectively, our results identify the brain as a new site of action for the anorexic and browning impact of β 3 AR activation. Copyright © 2017 the American Physiological Society.

  17. Iron-binding haemerythrin RING ubiquitin ligases regulate plant iron responses and accumulation

    Science.gov (United States)

    Kobayashi, Takanori; Nagasaka, Seiji; Senoura, Takeshi; Itai, Reiko Nakanishi; Nakanishi, Hiromi; Nishizawa, Naoko K.

    2013-01-01

    Iron is essential for most living organisms. Plants transcriptionally induce genes involved in iron acquisition under conditions of low iron availability, but the nature of the deficiency signal and its sensors are unknown. Here we report the identification of new iron regulators in rice, designated Oryza sativa Haemerythrin motif-containing Really Interesting New Gene (RING)- and Zinc-finger protein 1 (OsHRZ1) and OsHRZ2. OsHRZ1, OsHRZ2 and their Arabidopsis homologue BRUTUS bind iron and zinc, and possess ubiquitination activity. OsHRZ1 and OsHRZ2 are susceptible to degradation in roots irrespective of iron conditions. OsHRZ-knockdown plants exhibit substantial tolerance to iron deficiency, and accumulate more iron in their shoots and grains irrespective of soil iron conditions. The expression of iron deficiency-inducible genes involved in iron utilization is enhanced in OsHRZ-knockdown plants, mostly under iron-sufficient conditions. These results suggest that OsHRZ1 and OsHRZ2 are iron-binding sensors that negatively regulate iron acquisition under conditions of iron sufficiency. PMID:24253678

  18. Rictor/TORC2 regulates Caenorhabditis elegans fat storage, body size, and development through sgk-1.

    Directory of Open Access Journals (Sweden)

    Kevin T Jones

    2009-03-01

    Full Text Available The target of rapamycin (TOR kinase coordinately regulates fundamental metabolic and cellular processes to support growth, proliferation, survival, and differentiation, and consequently it has been proposed as a therapeutic target for the treatment of cancer, metabolic disease, and aging. The TOR kinase is found in two biochemically and functionally distinct complexes, termed TORC1 and TORC2. Aided by the compound rapamycin, which specifically inhibits TORC1, the role of TORC1 in regulating translation and cellular growth has been extensively studied. The physiological roles of TORC2 have remained largely elusive due to the lack of pharmacological inhibitors and its genetic lethality in mammals. Among potential targets of TORC2, the pro-survival kinase AKT has garnered much attention. Within the context of intact animals, however, the physiological consequences of phosphorylation of AKT by TORC2 remain poorly understood. Here we describe viable loss-of-function mutants in the Caenorhabditis elegans homolog of the TORC2-specific component, Rictor (CeRictor. These mutants display a mild developmental delay and decreased body size, but have increased lipid storage. These functions of CeRictor are not mediated through the regulation of AKT kinases or their major downstream target, the insulin-regulated FOXO transcription factor DAF-16. We found that loss of sgk-1, a homolog of the serum- and glucocorticoid-induced kinase, mimics the developmental, growth, and metabolic phenotypes of CeRictor mutants, while a novel, gain-of-function mutation in sgk-1 suppresses these phenotypes, indicating that SGK-1 is a mediator of CeRictor activity. These findings identify new physiological roles for TORC2, mediated by SGK, in regulation of C. elegans lipid accumulation and growth, and they challenge the notion that AKT is the primary effector of TORC2 function.

  19. Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

    DEFF Research Database (Denmark)

    McGlashon, Jacob M; Gorecki, Michelle C; Kozlowski, Amanda E

    2015-01-01

    Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human...... adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating...

  20. The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Michiko Koda

    2016-04-01

    Full Text Available Background: Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. Methods: The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers and their visceral fat area (VFA (<100 cm2 and ≥100 cm2. Results: The serum triglyceride (TG levels of 835 males were assessed. In the VFA ≥100 cm2 group, a significantly greater proportion of current smokers (47.3% exhibited TG levels of ≥150 mg/dL compared with former smokers (36.4% and non-smokers (18.8%. The difference in TG level distribution between former smokers and non-smokers was also significant. However, among the subjects with VFA of <100 cm2, the TG levels of the three smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c levels of 877 males were also assessed. In the VFA <100 cm2 group, significantly higher proportions of current smokers (17.9% and former smokers (14.9% demonstrated HbA1c levels of ≥5.6% compared with non-smokers (6.3%. In contrast, in the VFA ≥100 cm2 group, significantly fewer former smokers displayed HbA1c levels of ≥5.6% compared with non-smokers and current smokers. Furthermore, the interaction between smoking habits and VFA was associated with the subjects’ TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA. Conclusions: Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA.

  1. Protein Profiles for Muscle Development and Intramuscular Fat Accumulation at Different Post-Hatching Ages in Chickens.

    Directory of Open Access Journals (Sweden)

    Jie Liu

    Full Text Available Muscle development and growth influences the efficiency of poultry meat production, and is closely related to deposition of intramuscular fat (IMF, which is crucial in meat quality. To clarify the molecular mechanisms underlying muscle development and IMF deposition in chickens, protein expression profiles were examined in the breast muscle of Beijing-You chickens at ages 1, 56, 98 and 140 days, using isobaric tags for relative and absolute quantification (iTRAQ. Two hundred and four of 494 proteins were expressed differentially. The expression profile at day 1 differed greatly from those at day 56, 98 and 140. KEGG pathway analysis of differential protein expression from pair-wise comparisons (day 1 vs. 56; 56 vs. 98; 98 vs. 140, showed that the fatty acid degradation pathway was more active during the stage from day 1 to 56 than at other periods. This was consistent with the change in IMF content, which was highest at day 1 and declined dramatically thereafter. When muscle growth was most rapid (days 56-98, pathways involved in muscle development were dominant, including hypertrophic cardiomyopathy, dilated cardiomyopathy, cardiac muscle contraction, tight junctions and focal adhesion. In contrast with hatchlings, the fatty acid degradation pathway was downregulated from day 98 to 140, which was consistent with the period for IMF deposition following rapid muscle growth. Changes in some key specific proteins, including fast skeletal muscle troponin T isoform, aldehyde dehydrogenase 1A1 and apolipoprotein A1, were verified by Western blotting, and could be potential biomarkers for IMF deposition in chickens. Protein-protein interaction networks showed that ribosome-related functional modules were clustered in all three stages. However, the functional module involved in the metabolic pathway was only clustered in the first stage (day 1 vs. 56. This study improves our understanding of the molecular mechanisms underlying muscle development and IMF

  2. Physiology and biochemistry of source-regulated protein accumulation in the wheat grain.

    Science.gov (United States)

    Barneix, Atilio J

    2007-05-01

    Wheat is unique among cereals for the baking qualities of its flour, which are dependent upon the type and concentration of its proteins. As a consequence, the grain protein concentration (GPC) is one of the main determinants of wheat international market price. More than 50-70% of the final grain N is accumulated before flowering and later remobilized to the grain, N fertilization being the common practice used to produce high GPC. However, after incremental additions of N fertilizer, GPC reaches a maximum and then remains constant, without any increase in N uptake or remobilization by the crop, thus decreasing the efficiency of N fertilizer. Although, the genetic and molecular mechanisms that regulate N uptake by the roots are being clarified quickly, the regulation and physiology of N transport from the leaves to the grain remains less clear. In this review, the possible regulatory points involved in N transport to the grain and the difficulties for increasing GPC are discussed. It has been demonstrated that protein synthesis in the grain is source-limited, and that the grain can accumulate protein limited only by the amino acids provided by the phloem. It has also been shown that there is no limitation in the amino acid/sugar ratios that can be exported to the phloem. On the other hand, NO(3)(-) uptake transporters are depressed when the plant concentration of some amino acids, such as glutamine, is high. It has also been shown that a high N supply increases cytokinins concentration, preventing leaf senescence and proteolysis. Based on this information, it is postulated that there are two main regulatory points during grain filling when plant N status is ample. On the one hand, the N uptake transporters in the roots are depressed due to the high amino acids concentration in the tissues, and N uptake is low. On the other, a high amino acids concentration keeps the cytokinins level high, repressing leaf protein degradation and decreasing amino acid export to the

  3. Acute vs chronic exposure to high fat diet leads to distinct regulation of PKA.

    Science.gov (United States)

    London, Edra; Nesterova, Maria; Stratakis, Constantine A

    2017-07-01

    The cAMP-dependent protein kinase (PKA) is an essential regulator of lipid and glucose metabolism that plays a critical role in energy homeostasis. The impact of diet on PKA signaling has not been defined, although perturbations in individual PKA subunits are associated with changes in adiposity, physical activity and energy intake in mice and humans. We hypothesized that a high fat diet (HFD) would elicit peripheral and central alterations in the PKA system that would differ depending on length of exposure to HFD; these differences could protect against or promote diet-induced obesity (DIO). 12-week-old C57Bl/6J mice were randomly assigned to a regular diet or HFD and weighed weekly throughout the feeding studies (4 days, 14 weeks; respectively), and during killing. PKA activity and subunit expression were measured in liver, gonadal adipose tissue (AT) and brain. Acute HFD-feeding suppressed basal hepatic PKA activity. In contrast, hepatic and hypothalamic PKA activities were significantly increased after chronic HFD-feeding. Changes in AT were more subtle, and overall, altered PKA regulation in response to chronic HFD exposure was more profound in female mice. The suppression of hepatic PKA activity after 4 day HFD-feeding was indicative of a protective peripheral effect against obesity in the context of overnutrition. In response to chronic HFD-feeding, and with the development of DIO, dysregulated hepatic and hypothalamic PKA signaling was a signature of obesity that is likely to promote further metabolic dysfunction in mice. © 2017 Society for Endocrinology.

  4. Eating Regulation Styles, Appearance Schemas, and Body Satisfaction Predict Changes in Body Fat for Emerging Adults

    Science.gov (United States)

    Morgan, Ali Zaremba; Keiley, Margaret K.; Ryan, Aubrey E.; Radomski, Juliana Groves; Gropper, Sareen S.; Connell, Lenda Jo; Simmons, Karla P.; Ulrich, Pamela V.

    2012-01-01

    Obesity and high body fat percentages are a major public health issue. The percentage of obese and overweight Americans has increased over the past 30 years. On average, overweight individuals with higher percent body fat than normal weight individuals are at increased risk for numerous negative outcomes both physically and mentally. A prime time…

  5. Regulation and dysregulation of vitellogenin mRNA accumulation in daphnids (Daphnia magna)

    Energy Technology Data Exchange (ETDEWEB)

    Hannas, Bethany R.; Wang, Ying H.; Thomson, Susanne; Kwon, Gwijun; Hong, Li [Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695-7633 (United States); LeBlanc, Gerald A., E-mail: Gerald_LeBlanc@ncsu.edu [Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695-7633 (United States)

    2011-01-25

    The induction of vitellogenin in oviparous vertebrates has become the gold standard biomarker of exposure to estrogenic chemicals in the environment. This biomarker of estrogen exposure also has been used in arthropods, however, little is known of the factors that regulate the expression of vitellogenin in these organisms. We investigated changes in accumulation of mRNA products of the vitellogenin gene Vtg2 in daphnids (Daphnia magna) exposed to a diverse array of chemicals. We further evaluated the involvement of hormonal factors in the regulation of vitellogenin expression that may be targets of xenobiotic chemicals. Expression of the Vtg2 gene was highly responsive to exposure to various chemicals with an expression range spanning approximately four orders of magnitude. Chemicals causing the greatest induction were piperonyl butoxide, chlordane, 4-nonylphenol, cadmium, and chloroform. Among these, only 4-nonylphenol is recognized to be estrogenic. Exposure to several chemicals also suppressed Vtg2 mRNA levels, as much as 100-fold. Suppressive chemicals included cyproterone acetate, acetone, triclosan, and atrazine. Exposure to the estrogens diethylstilbestrol and bisphenol A had little effect on vitellogenin mRNA levels further substantiating that these genes are not induced by estrogen exposure. Exposure to the potent ecdysteroids 20-hydroxyecdysone and ponasterone A revealed that Vtg2 was subject to strong suppressive control by these hormones. Vtg2 mRNA levels were not significantly affected from exposure to several juvenoid hormones. Results indicate that ecdysteroids are suppressors of vitellogenin gene expression and that vitellogenin mRNA levels can be elevated or suppressed in daphnids by xenobiotics that elicit antiecdysteroidal or ecdysteroidal activity, respectively. Importantly, daphnid Vtg2 is not elevated in response to estrogenic activity.

  6. Regulation and dysregulation of vitellogenin mRNA accumulation in daphnids (Daphnia magna)

    International Nuclear Information System (INIS)

    Hannas, Bethany R.; Wang, Ying H.; Thomson, Susanne; Kwon, Gwijun; Li Hong; LeBlanc, Gerald A.

    2011-01-01

    The induction of vitellogenin in oviparous vertebrates has become the gold standard biomarker of exposure to estrogenic chemicals in the environment. This biomarker of estrogen exposure also has been used in arthropods, however, little is known of the factors that regulate the expression of vitellogenin in these organisms. We investigated changes in accumulation of mRNA products of the vitellogenin gene Vtg2 in daphnids (Daphnia magna) exposed to a diverse array of chemicals. We further evaluated the involvement of hormonal factors in the regulation of vitellogenin expression that may be targets of xenobiotic chemicals. Expression of the Vtg2 gene was highly responsive to exposure to various chemicals with an expression range spanning approximately four orders of magnitude. Chemicals causing the greatest induction were piperonyl butoxide, chlordane, 4-nonylphenol, cadmium, and chloroform. Among these, only 4-nonylphenol is recognized to be estrogenic. Exposure to several chemicals also suppressed Vtg2 mRNA levels, as much as 100-fold. Suppressive chemicals included cyproterone acetate, acetone, triclosan, and atrazine. Exposure to the estrogens diethylstilbestrol and bisphenol A had little effect on vitellogenin mRNA levels further substantiating that these genes are not induced by estrogen exposure. Exposure to the potent ecdysteroids 20-hydroxyecdysone and ponasterone A revealed that Vtg2 was subject to strong suppressive control by these hormones. Vtg2 mRNA levels were not significantly affected from exposure to several juvenoid hormones. Results indicate that ecdysteroids are suppressors of vitellogenin gene expression and that vitellogenin mRNA levels can be elevated or suppressed in daphnids by xenobiotics that elicit antiecdysteroidal or ecdysteroidal activity, respectively. Importantly, daphnid Vtg2 is not elevated in response to estrogenic activity.

  7. Conserved microRNA miR-8 in fat body regulates innate immune homeostasis in Drosophila.

    Science.gov (United States)

    Choi, In Kyou; Hyun, Seogang

    2012-05-01

    Antimicrobial peptides (AMPs) constitute a major arm of the innate immune system across diverse organisms. In Drosophila, septic injury by microbial pathogens rapidly induces the production of the AMPs in fat body via well elucidated pathways such as Toll and IMD. However, several epithelial tissues were reported to locally express AMPs without septic injury via poorly characterized ways. Here, we report that microRNA miR-8 regulates the levels of AMPs basally expressed in Drosophila. The levels of AMPs such as Drosomycin and Diptericin are significantly increased in miR-8 null animals in non-pathogen stimulated conditions. Analysis of various larval tissues revealed that the increase of Drosomycin is fat body specific. Supporting this observation, re-introduction of miR-8 only in the fat body restored the altered AMP expression in miR-8 null flies. Although loss of miR-8 impedes PI3K in the fat body, inhibition of PI3K does not phenocopy the AMP expression of miR-8 null flies, indicating that miR-8 regulates AMP independently of PI3K. Together, our findings suggest a role of miR-8 in systemic immune homeostasis in generally non-pathogenic conditions in flies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.

    Science.gov (United States)

    Walker, Paul D; Jarosz, Patricia A; Bouhamdan, Mohamad; MacKenzie, Robert G

    2015-01-01

    Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome. Copyright © 2014. Published by Elsevier Inc.

  9. Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions

    Directory of Open Access Journals (Sweden)

    Lingling Han

    2015-01-01

    Full Text Available This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA- induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4, AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase (ACC, and uncoupling protein 3 (UCP3 were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9 and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM, P<0.05 and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min, P<0.05. The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (all P<0.05, but those in the 10−9 and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (all P<0.05. In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation.

  10. Consumption of sucrose from infancy increases the visceral fat accumulation, concentration of triglycerides, insulin and leptin, and generates abnormalities in the adrenal gland.

    Science.gov (United States)

    Díaz-Aguila, Yadira; Castelán, Francisco; Cuevas, Estela; Zambrano, Elena; Martínez-Gómez, Margarita; Muñoz, Alvaro; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

    2016-03-01

    Consumption of sugar-sweetened beverages promotes the development of metabolic syndrome (MetS) and type 2 diabetes mellitus in humans. One factor related to the appearance of MetS components is the dysfunction of the adrenal gland. In fact, the experimental generation of hyperglycemia has been associated with morphological and microvascular changes in the adrenal glands of rats. We hypothesized that high sucrose consumption from infancy promotes histological disruption of the adrenal glands associated with the appearance of metabolic syndrome indicators. Male Wistar rats were separated at weaning (21 days old) into two groups: free access to tap water (control group, C) or 30 % sucrose diluted in water (sugar-fed group). After 12 weeks, high sucrose consumption promoted an increase in visceral fat accumulation, adipose cell number, and insulin resistance. Also, a rise in the concentration of triglycerides, very low-density lipoprotein, insulin and leptin was observed. In control rats, a histomorphometric asymmetry between the right and left adrenal glands was found. In the sugar-fed group, sucrose consumption produced a major change in adrenal gland asymmetry. No changes in corticosterone serum level were observed in either group. Our results suggest that a high sucrose liquid-diet from early life alters the morphology of adrenocortical zones, leading to MetS indicators.

  11. Abdominal visceral fat accumulation is associated with the results of 123I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

    International Nuclear Information System (INIS)

    Anan, Futoshi; Masaki, Takayuki; Takahashi, Naohiko; Yoshimatsu, Hironobu; Yonemochi, Hidetoshi; Nakagawa, Mikiko; Saikawa, Tetsunori; Eshima, Nobuoki

    2007-01-01

    We tested the hypothesis that increased abdominal visceral accumulation (VFA) is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The study group consisted of 24 type 2 diabetic patients with high VFA (≥100 cm 2 , age 60 ± 8 years, high VFA group). The control group consisted of 19 age-matched type 2 diabetic patients with normal VFA ( 2 , age 60 ± 7 years, normal VFA group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed 123 I-MIBG myocardial uptake values were lower (p 123 I-MIBG was higher (p 123 I-MIBG during the delayed phase. Our results demonstrate that the level of VFA is associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus. (orig.)

  12. The effect of eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma

    Directory of Open Access Journals (Sweden)

    Rouhollah Haghshenas

    2014-04-01

    Full Text Available Objective(s:Consumption of high-fat foods is one of the major causes of obesity. Physical exercise is a strategy used to counteract obesity. The aim of this study was to investigate the effect of eight weeks endurance training and high-fat diet (HFD on appetite-regulating hormones in rat plasma. Materials and Methods:Twenty eight male Wistar rats were randomly divided into four groups: Control group with standard diet (CSD, endurance training with a standard diet (ESD, control group with high-fat diet (CHFD and endurance training with high-fat diet (EHFD. Twenty-four hr after the last training session, the blood samples were obtained and analyzed for hormones levels. Results: The significant increased weight gain and food intake and decreased plasma nesfatin-1 and PYY3-36 levels were observed in CHFD group, while exercise under the HFD antagonized these effects. There were no significant changes in ghrelin, insulin and leptin levels in different groups. Conclusion: These results suggest that exercise can prevent fattening effect of HFD. Probably, performing exercise makes a reduction of food intake and weight gain in rat via the increase in nesfatin-1 and PYY levels. However, further studies are necessary to understand the exact mechanisms involved in this field.

  13. Ethylene regulation of carotenoid accumulation and carotenogenic gene expression in colour-contrasted apricot varieties (Prunus armeniaca).

    Science.gov (United States)

    Marty, I; Bureau, S; Sarkissian, G; Gouble, B; Audergon, J M; Albagnac, G

    2005-07-01

    In order to elucidate the regulation mechanisms of carotenoid biosynthesis in apricot fruit (Prunus armeniaca), carotenoid content and carotenogenic gene expression were analysed as a function of ethylene production in two colour-contrasted apricot varieties. Fruits from Goldrich (GO) were orange, while Moniqui (MO) fruits were white. Biochemical analysis showed that GO accumulated precursors of the uncoloured carotenoids, phytoene and phytofluene, and the coloured carotenoid, beta-carotene, while Moniqui (MO) fruits only accumulated phytoene and phytofluene but no beta-carotene. Physiological analysis showed that ethylene production was clearly weaker in GO than in MO. Carotenogenic gene expression (Psy-1, Pds, and Zds) and carotenoid accumulation were measured with respect to ethylene production which is initiated in mature green fruits at the onset of the climacteric stage or following exo-ethylene or ethylene-receptor inhibitor (1-MCP) treatments. Results showed (i) systematically stronger expression of carotenogenic genes in white than in orange fruits, even for the Zds gene involved in beta-carotene synthesis that is undetectable in MO fruits, (ii) ethylene-induction of Psy-1 and Pds gene expression and the corresponding product accumulation, (iii) Zds gene expression and beta-carotene production independent of ethylene. The different results obtained at physiological, biochemical, and molecular levels revealed the complex regulation of carotenoid biosynthesis in apricots and led to suggestions regarding some possible ways to regulate it.

  14. Vanillylacetone up-regulates anthocyanin accumulation and expression of anthocyanin biosynthetic genes by inducing endogenous abscisic acid in grapevine tissues.

    Science.gov (United States)

    Enoki, Shinichi; Hattori, Tomoki; Ishiai, Shiho; Tanaka, Sayumi; Mikami, Masachika; Arita, Kayo; Nagasaka, Shu; Suzuki, Shunji

    2017-12-01

    We investigated the effect of vanillylacetone (VA) on anthocyanin accumulation with aim of improving grape berry coloration. Spraying Vitis vinifera cv. Muscat Bailey A berries with VA at veraison increased sugar/acid ratio, an indicator of maturation and total anthocyanin accumulation. To elucidate the molecular mechanism underlying the effect of VA on anthocyanin accumulation, in vitro VA treatment of a grapevine cell culture was carried out. Endogenous abscisic acid (ABA) content was higher in the VA-treated cell cultures than in control at 3h after treatment. Consistent with this, the relative expression levels of anthocyanin-synthesis-related genes, including DFR, LDOX, MybA1 and UFGT, in VA-treated cell cultures were much higher than those in control, and high total anthocyanin accumulation was noted in the VA-treated cell cultures as well. These results suggest that VA up-regulates the expression of genes leading to anthocyanin accumulation by inducing endogenous ABA. In addition, VA increased total anthocyanin content in a dose-dependent manner. Although VA treatment in combination with exogenous ABA did not exhibit any synergistic effect, treatment with VA alone showed an equivalent effect to that with exogenous ABA alone on total anthocyanin accumulation. These findings point to the possibility of using VA for improving grape berry coloration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  15. FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice.

    Science.gov (United States)

    Le Foll, Christelle; Dunn-Meynell, Ambrose; Musatov, Serguei; Magnan, Christophe; Levin, Barry E

    2013-08-01

    Hypothalamic "metabolic-sensing" neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ~50% of these neurons responded to oleic acid (OA) by using the FA translocator/receptor FAT/CD36 (CD36). For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36 depletion, the percent of neurons that responded to OA was decreased specifically in glucosensing neurons. A similar effect was seen in total-body CD36-knockout mice. Next, weanling rats were injected in the VMH with CD36 AAV shRNA. Despite significant VMH CD36 depletion, there was no effect on food intake, body weight gain, or total carcass adiposity on chow or 45% fat diets. However, VMH CD36-depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance. These results demonstrate that CD36 is a critical factor in both VMH neuronal FA sensing and the regulation of energy and glucose homeostasis.

  16. The early activation marker CD69 regulates the expression of chemokines and CD4 T cell accumulation in intestine.

    Directory of Open Access Journals (Sweden)

    Katarina Radulovic

    Full Text Available Migration of naïve and activated lymphocytes is regulated by the expression of various molecules such as chemokine receptors and ligands. CD69, the early activation marker of C-type lectin domain family, is also shown to regulate the lymphocyte migration by affecting their egress from the thymus and secondary lymphoid organs. Here, we aimed to investigate the role of CD69 in accumulation of CD4 T cells in intestine using murine models of inflammatory bowel disease. We found that genetic deletion of CD69 in mice increases the expression of the chemokines CCL-1, CXCL-10 and CCL-19 in CD4(+ T cells and/or CD4(- cells. Efficient in vitro migration of CD69-deficient CD4 T cells toward the chemokine stimuli was the result of increased expression and/or affinity of chemokine receptors. In vivo CD69(-/- CD4 T cells accumulate in the intestine in higher numbers than B6 CD4 T cells as observed in competitive homing assay, dextran sodium sulphate (DSS-induced colitis and antigen-specific transfer colitis. In DSS colitis CD69(-/- CD4 T cell accumulation in colonic lamina propria (cLP was associated with increased expression of CCL-1, CXCL-10 and CCL-19 genes. Furthermore, treatment of DSS-administrated CD69(-/- mice with the mixture of CCL-1, CXCL-10 and CCL-19 neutralizing Abs significantly decreased the histopathological signs of colitis. Transfer of OT-II×CD69(-/- CD45RB(high CD4 T cells into RAG(-/- hosts induced CD4 T cell accumulation in cLP. This study showed CD69 as negative regulator of inflammatory responses in intestine as it decreases the expression of chemotactic receptors and ligands and reduces the accumulation of CD4 T cells in cLP during colitis.

  17. Abdominal visceral fat accumulation is associated with the results of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

    Energy Technology Data Exchange (ETDEWEB)

    Anan, Futoshi [Oita Red Cross Hospital, Department of Cardiology, Oita (Japan); Oita University, Department of Internal Medicine I, Oita (Japan); Masaki, Takayuki; Takahashi, Naohiko; Yoshimatsu, Hironobu [Oita University, Department of Internal Medicine I, Oita (Japan); Yonemochi, Hidetoshi; Nakagawa, Mikiko; Saikawa, Tetsunori [Oita University, Department of Cardiovascular Science, Oita (Japan); Eshima, Nobuoki [Oita University, Department of Biostatistics, School of Medicine, Oita (Japan)

    2007-08-15

    We tested the hypothesis that increased abdominal visceral accumulation (VFA) is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The study group consisted of 24 type 2 diabetic patients with high VFA ({>=}100 cm{sup 2}, age 60 {+-} 8 years, high VFA group). The control group consisted of 19 age-matched type 2 diabetic patients with normal VFA (<100 cm{sup 2}, age 60 {+-} 7 years, normal VFA group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed {sup 123}I-MIBG myocardial uptake values were lower (p < 0.005 and p < 0.0001, respectively) and the percent washout rate of {sup 123}I-MIBG was higher (p < 0.0005) in the high VFA group than in the normal VFA group. The fasting plasma insulin concentrations (p < 0.005) and the homeostasis model assessment (HOMA) index values (p < 0.0005) were higher in the high VFA group than in normal VFA group. Multiple regression analysis revealed that the level of VFA was independently predicted by the HOMA index values and the myocardial uptake of {sup 123}I-MIBG during the delayed phase. Our results demonstrate that the level of VFA is associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus. (orig.)

  18. Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha

    NARCIS (Netherlands)

    Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P.; Li, Dan L.; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F.; Tschöp, Matthias H.; Clegg, Deborah J.

    2014-01-01

    High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha

  19. Role of PTP1B in POMC neurons during chronic high-fat diet: sex differences in regulation of liver lipids and glucose tolerance.

    Science.gov (United States)

    Aberdein, Nicola; Dambrino, Robert J; do Carmo, Jussara M; Wang, Zhen; Mitchell, Laura E; Drummond, Heather A; Hall, John E

    2018-03-01

    Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin receptor signaling and may contribute to leptin resistance in diet-induced obesity. Although PTP1B inhibition has been suggested as a potential weight loss therapy, the role of specific neuronal PTP1B signaling in cardiovascular and metabolic regulation and the importance of sex differences in this regulation are still unclear. In this study, we investigated the impact of proopiomelanocortin (POMC) neuronal PTP1B deficiency in cardiometabolic regulation in male and female mice fed a high-fat diet (HFD). When compared with control mice (PTP1B flox/flox ), male and female mice deficient in POMC neuronal PTP1B (PTP1B flox/flox /POMC-Cre) had attenuated body weight gain (males: -18%; females: -16%) and fat mass (males: -33%; female: -29%) in response to HFD. Glucose tolerance was improved by 40%, and liver lipid accumulation was reduced by 40% in PTP1B/POMC-Cre males but not in females. When compared with control mice, deficiency of POMC neuronal PTP1B did not alter mean arterial pressure (MAP) in male or female mice (males: 112 ± 1 vs. 112 ± 1 mmHg in controls; females: 106 ± 3 vs. 109 ± 3 mmHg in controls). Deficiency of POMC neuronal PTP1B also did not alter MAP response to acute stress in males or females compared with control mice (males: Δ32 ± 0 vs. Δ29 ± 4 mmHg; females: Δ22 ± 2 vs. Δ27 ± 4 mmHg). These data demonstrate that POMC-specific PTP1B deficiency improved glucose tolerance and attenuated diet-induced fatty liver only in male mice and attenuated weight gain in males and females but did not enhance the MAP and HR responses to a HFD or to acute stress.

  20. Abscisic acid regulates pinoresinol-lariciresinol reductase gene expression and secoisolariciresinol accumulation in developing flax (Linum usitatissimum L.) seeds.

    Science.gov (United States)

    Renouard, Sullivan; Corbin, Cyrielle; Lopez, Tatiana; Montguillon, Josiane; Gutierrez, Laurent; Lamblin, Frédéric; Lainé, Eric; Hano, Christophe

    2012-01-01

    Secoisolariciresinol diglucoside (SDG), the main phytoestrogenic lignan of Linum usitatissimum, is accumulated in the seed coat of flax during its development and pinoresinol-lariciresinol reductase (PLR) is a key enzyme in flax for its synthesis. The promoter of LuPLR1, a flax gene encoding a pinoresinol lariciresinol reductase, contains putative regulatory boxes related to transcription activation by abscisic acid (ABA). Gel mobility shift experiments evidenced an interaction of nuclear proteins extracted from immature flax seed coat with a putative cis-acting element involved in ABA response. As ABA regulates a number of physiological events during seed development and maturation we have investigated its involvement in the regulation of this lignan synthesis by different means. ABA and SDG accumulation time courses in the seed as well as LuPLR1 expression were first determined in natural conditions. These results showed that ABA timing and localization of accumulation in the flax seed coat could be correlated with the LuPLR1 gene expression and SDG biosynthesis. Experimental modulations of ABA levels were performed by exogenous application of ABA or fluridone, an inhibitor of ABA synthesis. When submitted to exogenous ABA, immature seeds synthesized 3-times more SDG, whereas synthesis of SDG was reduced in immature seeds treated with fluridone. Similarly, the expression of LuPLR1 gene in the seed coat was up-regulated by exogenous ABA and down-regulated when fluridone was applied. These results demonstrate that SDG biosynthesis in the flax seed coat is positively controlled by ABA through the transcriptional regulation of LuPLR1 gene.

  1. Carotenoid accumulation in orange-pigmented Capsicum annuum fruit, regulated at multiple levels

    Science.gov (United States)

    Rodriguez-Uribe, Laura; Guzman, Ivette; Rajapakse, Wathsala; Richins, Richard D.; O’Connell, Mary A.

    2012-01-01

    The pericarp of Capsicum fruit is a rich dietary source of carotenoids. Accumulation of these compounds may be controlled, in part, by gene transcription of biosynthetic enzymes. The carotenoid composition in a number of orange-coloured C. annuum cultivars was determined using HPLC and compared with transcript abundances for four carotenogenic enzymes, Psy, LcyB, CrtZ-2, and Ccs determined by qRT-PCR. There were unique carotenoid profiles as well as distinct patterns of transcription of carotenogenic enzymes within the seven orange-coloured cultivars. In one cultivar, ‘Fogo’, carrying the mutant ccs-3 allele, transcripts were detected for this gene, but no CCS protein accumulated. The premature stop termination in ccs-3 prevented expression of the biosynthetic activity to synthesize the capsanthin and capsorubin forms of carotenoids. In two other orange-coloured cultivars, ‘Orange Grande’ and ‘Oriole’, both with wild-type versions of all four carotenogenic enzymes, no transcripts for Ccs were detected and no red pigments accumulated. Finally, in a third case, the orange-coloured cultivar, Canary, transcripts for all four of the wild-type carotenogenic enzymes were readily detected yet no CCS protein appeared to accumulate and no red carotenoids were synthesized. In the past, mutations in Psy and Ccs have been identified as the loci controlling colour in the fruit. Now there is evidence that a non-structural gene may control colour development in Capsicum. PMID:21948863

  2. Life in the fat lane: seasonal regulation of insulin sensitivity, food intake, and adipose biology in brown bears.

    Science.gov (United States)

    Rigano, K S; Gehring, J L; Evans Hutzenbiler, B D; Chen, A V; Nelson, O L; Vella, C A; Robbins, C T; Jansen, H T

    2017-05-01

    Grizzly bears (Ursus arctos horribilis) have evolved remarkable metabolic adaptations including enormous fat accumulation during the active season followed by fasting during hibernation. However, these fluctuations in body mass do not cause the same harmful effects associated with obesity in humans. To better understand these seasonal transitions, we performed insulin and glucose tolerance tests in captive grizzly bears, characterized the annual profiles of circulating adipokines, and tested the anorectic effects of centrally administered leptin at different times of the year. We also used bear gluteal adipocyte cultures to test insulin and beta-adrenergic sensitivity in vitro. Bears were insulin resistant during hibernation but were sensitive during the spring and fall active periods. Hibernating bears remained euglycemic, possibly due to hyperinsulinemia and hyperglucagonemia. Adipokine concentrations were relatively low throughout the active season but peaked in mid-October prior to hibernation when fat content was greatest. Serum glycerol was highest during hibernation, indicating ongoing lipolysis. Centrally administered leptin reduced food intake in October, but not in August, revealing seasonal variation in the brain's sensitivity to its anorectic effects. This was supported by strong phosphorylated signal transducer and activator of transcription 3 labeling within the hypothalamus of hibernating bears; labeling virtually disappeared in active bears. Adipocytes collected during hibernation were insulin resistant when cultured with hibernation serum but became sensitive when cultured with active season serum. Heat treatment of active serum blocked much of this action. Clarifying the cellular mechanisms responsible for the physiology of hibernating bears may inform new treatments for metabolic disorders.

  3. Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.

    Science.gov (United States)

    Shamansurova, Zulaykho; Tan, Paul; Ahmed, Basma; Pepin, Emilie; Seda, Ondrej; Lavoie, Julie L

    2016-10-01

    We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. KO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. (P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

  4. Salinity-dependent nickel accumulation and effects on respiration, ion regulation and oxidative stress in the galaxiid fish, Galaxias maculatus.

    Science.gov (United States)

    Blewett, Tamzin A; Wood, Chris M; Glover, Chris N

    2016-07-01

    Inanga (Galaxias maculatus) are a euryhaline and amphidromous Southern hemisphere fish species inhabiting waters highly contaminated in trace elements such as nickel (Ni). Ni is known to exert its toxic effects on aquatic biota via three key mechanisms: inhibition of respiration, impaired ion regulation, and stimulation of oxidative stress. Inanga acclimated to freshwater (FW), 50% seawater (SW) or 100% SW were exposed to 0, 150 or 2000 μg Ni L(-1), and tissue Ni accumulation, metabolic rate, ion regulation (tissue ions, calcium (Ca) ion influx), and oxidative stress (catalase activity, protein carbonylation) were measured after 96 h. Ni accumulation increased with Ni exposure concentration in gill, gut and remaining body, but not in liver. Only in the gill was Ni accumulation affected by exposure salinity, with lower branchial Ni burdens in 100% and 50% SW inanga, relative to FW fish. There were no Ni-dependent effects on respiration, or Ca influx, and the only Ni-dependent effect on tissue ion content was on gill potassium. Catalase activity and protein carbonylation were affected by Ni, primarily in FW, but only at 150 μg Ni L(-1). Salinity therefore offsets the effects of Ni, despite minimal changes in Ni bioavailability. These data suggest only minor effects of Ni in inanga, even at highly elevated environmental Ni concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

    Directory of Open Access Journals (Sweden)

    Marta Moya

    Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

  6. Obesity-related polymorphisms and their associations with the ability to regulate fat oxidation in obese europeans

    DEFF Research Database (Denmark)

    Corpeleijn, Eva; Petersen, Liselotte; Holst, Claus

    2010-01-01

    for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese......Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single-nucleotide polymorphisms (SNPs) in 26 candidate genes.......01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with -174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related...

  7. Bisphenol A accumulation in eggs disrupts the endocrine regulation of growth in rainbow trout larvae

    Energy Technology Data Exchange (ETDEWEB)

    Birceanu, Oana; Servos, Mark R.; Vijayan, Mathilakath M., E-mail: matt.vijayan@ucalgary.ca

    2015-04-15

    Highlights: • BPA in eggs reduces growth and increases food conversion ratio in trout larvae. • BPA in eggs disrupts larval transcript abundance of genes involved in GH/IGF axis. • BPA in eggs disrupts thyroid hormone receptor mRNA levels. • BPA in eggs consistently suppressed IGF-1rb mRNA levels during early development. - Abstract: Bisphenol A (BPA), a monomer used in the production of plastics and epoxy resins, is ubiquitously present in the aquatic environment. BPA is considered a weak estrogen in fish, but the effects of this chemical on early developmental events are far from clear. We tested the hypothesis that BPA accumulation in eggs, mimicking maternal transfer, disrupts growth hormone/insulin-like growth factor (GH/IGF) axis function, leading to defects in larval growth in rainbow trout. Trout oocytes were exposed to 0 (control), 0.3, 3, and 30 μg ml{sup −1} BPA for 3 h, which led to an accumulation of around 0, 1, 4 and 40 ng BPA per egg, respectively. All treatment groups were fertilized with clean milt and reared in clean water for the rest of the experiment. The embryo BPA content declined over time in all groups and was completely eliminated by 42 days post-fertilization (dpf). Hatchlings from BPA accumulated eggs had higher water content and reduced total energy levels prior to first feed. There was an overall reduction in the specific growth rate and food conversion ratio in larvae reared from BPA-laden eggs. BPA accumulation disrupted the mRNA abundance of genes involved in GH/IGF axis function, including GH isoforms and their receptors, IGF-1 and -2 and IGF receptors, in a life stage-dependent manner. Also, there was a temporal disruption in the mRNA levels of thyroid hormone receptors in the larvae raised from BPA-laden eggs. Altogether, BPA accumulation in eggs, mimicking maternal transfer, affects larval growth and the mode of action involves disruption of genes involved in the GH/IGF and thyroid axes function in trout.

  8. Bisphenol A accumulation in eggs disrupts the endocrine regulation of growth in rainbow trout larvae

    International Nuclear Information System (INIS)

    Birceanu, Oana; Servos, Mark R.; Vijayan, Mathilakath M.

    2015-01-01

    Highlights: • BPA in eggs reduces growth and increases food conversion ratio in trout larvae. • BPA in eggs disrupts larval transcript abundance of genes involved in GH/IGF axis. • BPA in eggs disrupts thyroid hormone receptor mRNA levels. • BPA in eggs consistently suppressed IGF-1rb mRNA levels during early development. - Abstract: Bisphenol A (BPA), a monomer used in the production of plastics and epoxy resins, is ubiquitously present in the aquatic environment. BPA is considered a weak estrogen in fish, but the effects of this chemical on early developmental events are far from clear. We tested the hypothesis that BPA accumulation in eggs, mimicking maternal transfer, disrupts growth hormone/insulin-like growth factor (GH/IGF) axis function, leading to defects in larval growth in rainbow trout. Trout oocytes were exposed to 0 (control), 0.3, 3, and 30 μg ml −1 BPA for 3 h, which led to an accumulation of around 0, 1, 4 and 40 ng BPA per egg, respectively. All treatment groups were fertilized with clean milt and reared in clean water for the rest of the experiment. The embryo BPA content declined over time in all groups and was completely eliminated by 42 days post-fertilization (dpf). Hatchlings from BPA accumulated eggs had higher water content and reduced total energy levels prior to first feed. There was an overall reduction in the specific growth rate and food conversion ratio in larvae reared from BPA-laden eggs. BPA accumulation disrupted the mRNA abundance of genes involved in GH/IGF axis function, including GH isoforms and their receptors, IGF-1 and -2 and IGF receptors, in a life stage-dependent manner. Also, there was a temporal disruption in the mRNA levels of thyroid hormone receptors in the larvae raised from BPA-laden eggs. Altogether, BPA accumulation in eggs, mimicking maternal transfer, affects larval growth and the mode of action involves disruption of genes involved in the GH/IGF and thyroid axes function in trout

  9. Fat metabolism is regulated by altered gene expression oflipogenic enzymes and regulatory factors in liver and adiposetissue but not in semimembranosus muscle of pigs during thefattening period

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte

    2009-01-01

    It has been shown previously that lipid metabolism is regulated by fatty acids (FA) and that thyroid hormones are important regulators of energy metabolism. The effects of weight, dietary fat level and dietary FA profile on thyroid hormone levels and expression of lipogenic genes and tissue FA co...

  10. FGT-1 is a mammalian GLUT2-like facilitative glucose transporter in Caenorhabditis elegans whose malfunction induces fat accumulation in intestinal cells.

    Directory of Open Access Journals (Sweden)

    Shun Kitaoka

    Full Text Available Caenorhabditis elegans (C. elegans is an attractive animal model for biological and biomedical research because it permits relatively easy genetic dissection of cellular pathways, including insulin/IGF-like signaling (IIS, that are conserved in mammalian cells. To explore C. elegans as a model system to study the regulation of the facilitative glucose transporter (GLUT, we have characterized the GLUT gene homologues in C. elegans: fgt-1, R09B5.11, C35A11.4, F53H8.3, F48E3.2, F13B12.2, Y61A9LA.1, K08F9.1 and Y37A1A.3. The exogenous expression of these gene products in Xenopus oocytes showed transport activity to unmetabolized glucose analogue 2-deoxy-D-glucose only in FGT-1. The FGT-1-mediated transport activity was inhibited by the specific GLUT inhibitor phloretin and exhibited a Michaelis constant (Km of 2.8 mM. Mannose, galactose, and fructose were able to inhibit FGT-1-mediated 2-deoxy-D-glucose uptake (P < 0.01, indicating that FGT-1 is also able to transport these hexose sugars. A GFP fusion protein of FGT-1 was observed only on the basolateral membrane of digestive tract epithelia in C. elegans, but not in other tissues. FGT-1::eGFP expression was observed from early embryonic stages. The knockdown or mutation of fgt-1 resulted in increased fat staining in both wild-type and daf-2 (mammalian insulin receptor homologue mutant animals. Other common phenotypes of IIS mutant animals, including dauer formation and brood size reduction, were not affected by fgt-1 knockdown in wild-type or daf-2 mutants. Our results indicated that in C. elegans, FGT-1 is mainly a mammalian GLUT2-like intestinal glucose transporter and is involved in lipid metabolism.

  11. Cobalt-chromium-molybdenum alloy causes metal accumulation and metallothionein up-regulation in rat liver and kidney

    DEFF Research Database (Denmark)

    Jakobsen, Stig Storgaard; Danscher, Gorm; Stoltenberg, Meredin

    2007-01-01

    in liver and kidney. We found that metal ions are liberated from CoCrMo alloys and suggest that they are released by dissolucytosis, a process where macrophages causes the metallic surface to release metal ions. Animals with intramuscular implants accumulated metal in liver and kidney and metallohionein I....../II were elevated in liver tissue. The present data do not tell whether kidney and liver are the primary target organs or what possible toxicological effect the different metal ions might have, but they show that metal ions are liberated from CoCrMo alloys that are not subjected to mechanical wear...... and that they accumulate in liver and kidney tissue. That the liberated metal ions affect the tissues is supported by an up-regulation of the detoxifying/pacifying metalloprotein I/II in the liver. Udgivelsesdato: 2007-Dec...

  12. Fat mass and obesity associated gene (FTO expression is regulated negatively by the transcription factor Foxa2.

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    Jianjin Guo

    Full Text Available Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. To investigate the transcriptional regulation of FTO expression, we created 5'-deletion constructs of the FTO promoter to determine which transcription factors are most relevant to FTO expression. The presence of an activation region at -201/+34 was confirmed by luciferase activity analysis. A potential Foxa2 (called HNF-3β binding site and an upstream stimulatory factor (USF-binding site was identified in the -100 bp fragment upstream of the transcription start site (TSS. Furthermore, using mutagenesis, we identified the Foxa2 binding sequence (-26/-14 as a negative regulatory element to the activity of the human FTO promoter. The USF binding site did not affect the FTO promoter activity. Chromatin immunoprecipitation (ChIP assays were performed to confirm Foxa2 binding to the FTO promoter. Overexpression of Foxa2 in HEK 293 cells significantly down-regulated FTO promoter activity and expression. Conversely, knockdown of Foxa2 by siRNA significantly up-regulated FTO expression. These findings suggest that Foxa2 negatively regulates the basal transcription and expression of the human FTO gene.

  13. High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

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    Napolitano Mariarosaria

    2011-04-01

    Full Text Available Abstract Background Hyperhomocysteinemia (HHcy causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD in rats were investigated. Methods and results After feeding rats a standard low fat diet (control or a high fat diet (57% metabolisable energy as fat for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS and cystathionine γ-lyase (CGS, the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group. Conclusions These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.

  14. Adipose tissue (PRR regulates insulin sensitivity, fat mass and body weight

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    Zulaykho Shamansurova

    2016-10-01

    Full Text Available Objective: We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(PRR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (PRR gene would prevent weight gain and insulin resistance. Methods: An adipose tissue-specific (PRR knockout (KO mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (PRR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. Results: KO mice had lower body weights compared to wild-types (WT. Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (PRR. Conclusions: (PRR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes. Keywords: (Prorenin receptor, Renin-angiotensin system, Adipose

  15. Acute and perinatal-programming effects of a fat-rich diet on rat muscle mitochondrial function and hepatic lipid accumulation

    DEFF Research Database (Denmark)

    Hellgren, Lars; Jensen, Runa I.; Waterstradt, Michelle S. G.

    2014-01-01

    respiratory control ratio with pyruvate, increased post weaning (p hepatic steatosis......Objective. Maternal high-fat intake during pregnancy may have long-term consequences in the offspring. Since this might relate to the capacity of mitochondrial metabolic adaptation and hepatic lipid metabolism, we investigated how maternal high-fat intake affected mitochondrial function and hepatic...... steatosis in the offspring. Design. Sprague–Dawley rats were fed a high-fat (20% w/w) or a control diet (chow, C) from 10 days before pregnancy and throughout lactation. At weaning the litters were split into two groups; one was continued on the maternal diet and the other was fed low-fat chow. Sample...

  16. Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei

    2017-01-01

    correlation was observed between the responses on the transcript and protein levels. Combination of DGA1 overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular......, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered...

  17. Effects of Chowiseungcheng-tang Extracts on the Preadipocytes Proliferation in 3T3-L1 cell line, Lipolysis of Adipocytes in rat, and Localized Fat Accumulation by extraction methods

    Directory of Open Access Journals (Sweden)

    Jae-eun, Lee

    2008-03-01

    Full Text Available Objectives : The purpose of this study is to investigate the effects of Chowiseungcheng-tang extracts on the preadipocytes proliferation in 3T3-L1 cell line, lipolysis of adipocytes in rat’s epididymal adipocytes and localized fat accumulation of porcine by extraction methods(alcohol and water. Methods : Diminish preadipocytes proliferation and promote lipolysis of adipocytes do primary role to reduce obesity. So, we used 3T3-L1 mouse embryo fibroblasts(preadipocytes and rat epididymal adipocytes from Sprague-Dawley rats to investigate the effects of Chowiseungcheng-tang extracts on the preadipocytes proliferation, lipolysis of adipocytes. They were treated with 0.01, 0.1, 1.0㎎/㎖ Chowiseungcheng-tang alcohol and water extracts. And for the purpose of investigating the effects of Chowiseungcheng-tang alcohol and water extracts on the localized fat accumulation, we injected 0.1, 1.0, 10.0㎎/㎖ Chowiseungcheng-tang extracts to porcine fat tissues and observed histological changes of them. Results : Following results were obtained from the preadipocytes proliferation and lipolysis of adipocytes and histological investigation of fat tissues. 1. Chowiseungcheng-tang extracts suppressed preadipocytes proliferation on the high dosage(especially 1.0㎎/㎖, and especially alcohol extracts had better effects. 2. The alcohol extracts of Chowiseungcheng-tang decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH on the concentrations of 0.1, 1.0㎎/㎖. Alcohol extracts had better effects than water extracts. 3. Chowiseungcheng-tang extracts increased lipolysis of adipocytes on the concentrations of 0.1, 1.0㎎/㎖, and especially on the concentration of 1.0㎎/㎖ alcohol extract of Chowiseungcheng-tang had better effect. 4. The water extract of Chowiseungcheng-tang had significant activity to the destruction of porcine fat cell membranes only on the concentration of 10.0㎎/㎖, but alcohol extracts of Chowiseungcheng-tang had it on all

  18. Nutritional Factors Affecting Abdominal Fat Deposition in Poultry: A Review

    Science.gov (United States)

    Fouad, A. M.; El-Senousey, H. K.

    2014-01-01

    The major goals of the poultry industry are to increase the carcass yield and to reduce carcass fatness, mainly the abdominal fat pad. The increase in poultry meat consumption has guided the selection process toward fast-growing broilers with a reduced feed conversion ratio. Intensive selection has led to great improvements in economic traits such as body weight gain, feed efficiency, and breast yield to meet the demands of consumers, but modern commercial chickens exhibit excessive fat accumulation in the abdomen area. However, dietary composition and feeding strategies may offer practical and efficient solutions for reducing body fat deposition in modern poultry strains. Thus, the regulation of lipid metabolism to reduce the abdominal fat content based on dietary composition and feeding strategy, as well as elucidating their effects on the key enzymes associated with lipid metabolism, could facilitate the production of lean meat and help to understand the fat-lowering effects of diet and different feeding strategies. PMID:25050050

  19. PPARα autocrine regulation of Ca²⁺-regulated exocytosis in guinea pig antral mucous cells: NO and cGMP accumulation.

    Science.gov (United States)

    Tanaka, Saori; Sugiyama, Nanae; Takahashi, Yuko; Mantoku, Daiki; Sawabe, Yukinori; Kuwabara, Hiroko; Nakano, Takashi; Shimamoto, Chikao; Matsumura, Hitoshi; Marunaka, Yoshinori; Nakahari, Takashi

    2014-12-15

    In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells. Copyright © 2014 the American Physiological Society.

  20. Soybean (Glycine max) WRINKLED1 transcription factor, GmWRI1a, positively regulates seed oil accumulation.

    Science.gov (United States)

    Chen, Liang; Zheng, Yuhong; Dong, Zhimin; Meng, Fanfan; Sun, Xingmiao; Fan, Xuhong; Zhang, Yunfeng; Wang, Mingliang; Wang, Shuming

    2018-04-01

    Soybean is the world's most important leguminous crop producing high-quality protein and oil. Elevating oil accumulation in soybean seed is always many researchers' goal. WRINKLED1 (WRI1) encodes a transcription factor of the APETALA2/ethylene responsive element-binding protein (AP2/EREBP) family that plays important roles during plant seed oil accumulation. In this study, we isolated and characterized three distinct orthologues of WRI1 in soybean (Glycine max) that display different organ-specific expression patterns, among which GmWRI1a was highly expressed in maturing soybean seed. Electrophoretic mobility shift assays and yeast one-hybrid experiments demonstrated that the GmWRI1a protein was capable of binding to AW-box, a conserved sequence in the proximal upstream regions of many genes involved in various steps of oil biosynthesis. Transgenic soybean seeds overexpressing GmWRI1a under the control of the seed-specific napin promoter showed the increased total oil and fatty acid content and the changed fatty acid composition. Furthermore, basing on the activated expressions in transgenic soybean seeds and existence of AW-box element in the promoter regions, direct downstream genes of GmWRI1a were identified, and their products were responsible for fatty acid production, elongation, desaturation and export from plastid. We conclude that GmWRI1a transcription factor can positively regulate oil accumulation in soybean seed by a complex gene expression network related to fatty acid biosynthesis.

  1. Dynein-Based Accumulation of Membranes Regulates Nuclear Expansion in Xenopus laevis Egg Extracts.

    Science.gov (United States)

    Hara, Yuki; Merten, Christoph A

    2015-06-08

    Nuclear size changes dynamically during development and has long been observed to correlate with the space surrounding the nucleus, as well as with the volume of the cell. Here we combine an in vitro cell-free system of Xenopus laevis egg extract with microfluidic devices to systematically analyze the effect of spatial constraints. The speed of nuclear expansion depended on the available space surrounding the nucleus up to a threshold volume in the nanoliter range, herein referred to as the nuclear domain. Under spatial constraints smaller than this nuclear domain, the size of microtubule-occupied space surrounding the nucleus turned out to be limiting for the accumulation of membranes around the nucleus via the motor protein dynein, therefore determining the speed of nuclear expansion. This mechanism explains how spatial information surrounding the nucleus, such as the positioning of the nucleus inside the cell, can control nuclear expansion. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Light spectrum regulates cell accumulation during daytime in the raphidophyte Chattonella antiqua causing noxious red tides.

    Science.gov (United States)

    Shikata, Tomoyuki; Matsunaga, Shigeru; Kuwahara, Yusuke; Iwahori, Sho; Nishiyama, Yoshitaka

    2016-07-01

    Most marine raphidophyte species cause noxious red tides in temperate coastal areas around the world. It is known that swimming abilities enable raphidophytes to accumulation of cells and to actively acquire light at surface layers and nutrients over a wide depth range. However, it remains unclear how the swimming behavior is affected by environmental conditions, especially light condition. In the present study, we observed the accumulation of the harmful red-tide raphidophyte Chattonella antiqua under various light conditions during the daytime in the laboratory. When exposed to ultraviolet-A/blue light (320-480nm) or red light (640-680nm) from above, cells moved downward. In the case of blue light (455nm), cells started to swim downward after 5-15min of irradiation at a photon flux density≥10μmolm(-2)s(-1). When exposed to monochromatic lights (400-680nm) from the side, cells moved away from the blue light source and then descended, but just moved downward under red light. However, mixing of green/orange light (520-630nm) diminished the effects of blue light. When exposed to a mixture of 30μmolm(-2)s(-1) of blue light (440nm) and ≥6μmolm(-2)s(-1) of yellow light (560nm) from above, cells did not move downward. These results indicate that blue light induces negative phototaxis and ultraviolet-A/blue and red lights induce descending, and green/orange light cancels out their effects in C. antiqua. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Browning and graying: novel transcriptional regulators of brown and beige fat tissues and aging

    Directory of Open Access Journals (Sweden)

    Elisabetta eMueller

    2016-03-01

    Full Text Available Obesity represents a major risk factor for the development of a number of metabolic disorders, including cardiovascular disease and type 2 diabetes. Since the discovery that brown and beige fat cells exist in adult humans and contribute to energy expenditure, increasing interest has been devoted to the understanding of the molecular switches turning on calorie utilization. It has been reported that the ability of thermogenic tissues to burn energy declines during aging, possibly contributing to the development of metabolic dysfunction late in life. This review will focus on the recently identified transcriptional modulators of brown and beige cells and will discuss the potential impact of some of these thermogenic factors on age-associated metabolic disorders.

  4. Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis.

    Science.gov (United States)

    McGlashon, Jacob M; Gorecki, Michelle C; Kozlowski, Amanda E; Thirnbeck, Caitlin K; Markan, Kathleen R; Leslie, Kirstie L; Kotas, Maya E; Potthoff, Matthew J; Richerson, George B; Gillum, Matthew P

    2015-05-05

    Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. The endogenous plant hormones and ratios regulate sugar and dry matter accumulation in Jerusalem artichoke in salt-soil.

    Science.gov (United States)

    Li, Lingling; Shao, Tianyun; Yang, Hui; Chen, Manxia; Gao, Xiumei; Long, Xiaohua; Shao, Hongbo; Liu, Zhaopu; Rengel, Zed

    2017-02-01

    The changes in content of endogenous hormones in stolons and tubers of Jerusalem artichoke (Helianthus tuberosus L.) regulate tuber growth, but the specific knowledge about the importance of balance among the endogenous hormones is lacking. Two varieties of Jerusalem artichoke (NY-1 and QY-2) were tested for the endogenous zeatin (ZT), auxins (IAA), gibberellins (GA 3 ) and abscisic acid (ABA) in regulating sugar and dry matter accumulation in tubers. The dry matter content and sugar accumulation in tubers were correlated positively with endogenous ZT and negatively with GA 3 content and GA 3 /ABA and IAA/ABA content ratios. Throughout the tuber formation, ZT content was higher in NY-1 than QY-2 tubers, whereas ABA content was higher in QY-2 than NY-1 tubers. The content ratios GA 3 /ABA and IAA/ABA were greater in NY-1 than QY-2 before tuber initiation, but QY-2 surpassed NY-1 during the tuber growth stage. The GA 3 /ABA and IAA/ABA content ratios declined during tuber growth. The results suggested that a dynamic balance of endogenous hormones played an important role in tuber development. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Wrinkled1 accelerates flowering and regulates lipid homeostasis between oil accumulation and membrane lipid anabolism in Brassica napus

    Directory of Open Access Journals (Sweden)

    Qing eLi

    2015-11-01

    Full Text Available Wrinkled1 (WRI1 belongs to the APETALA2 transcription factor family; it is unique to plants and is a central regulator of oil synthesis in Arabidopsis. The effects of WRI1 on comprehensive lipid metabolism and plant development were unknown, especially in crop plants. This study found that BnWRI1 in Brassica napus accelerated flowering and enhanced oil accumulation in both seeds and leaves without leading to a visible growth inhibition. BnWRI1 decreased storage carbohydrates and increased soluble sugars to facilitate the carbon flux to lipid anabolism. BnWRI1 is localized to the nucleus and directly binds to the AW-box at proximal upstream regions of genes involved in fatty acid synthesis and lipid assembly. The overexpression (OE of BnWRI1 resulted in the up-regulation of genes involved in glycolysis, fatty acid synthesis, lipid assembly, and flowering. Lipid profiling revealed increased galactolipid monogalactosyldiacylglycerol (MGDG, digalactosyldiacylglycerol (DGDG, and phosphatidylcholine (PC in the leaves of OE plants, whereas it exhibited a reduced level of the galactolipids DGDG and MGDG and increased levels of PC, phosphatidylethanolamide (PE, and oil (triacylglycerol, TAG in the siliques of OE plants during the early seed development stage. These results suggest that BnWRI1 is important for homeostasis among TAG, membrane lipids and sugars, and thus facilitates flowering and oil accumulation in B. napus.

  7. Netrin-1 regulates fibrocyte accumulation in the decellularized fibrotic scleroderma lung microenvironment and in bleomycin induced pulmonary fibrosis

    Science.gov (United States)

    Sun, Huanxing; Zhu, Yangyang; Pan, Hongyi; Chen, Xiaosong; Balestrini, Jenna L.; Lam, TuKiet T.; Kanyo, Jean E.; Eichmann, Anne; Gulati, Mridu; Fares, Wassim H.; Bai, Hanwen; Feghali-Bostwick, Carol A.; Gan, Ye; Peng, Xueyan; Moore, Meagan W.; White, Eric S.; Sava, Parid; Gonzalez, Anjelica L.; Cheng, Yuwei; Niklason, Laura E.; Herzog, Erica L.

    2017-01-01

    Objectives Fibrocytes are collagen-producing leukocytes that accumulate in Scleroderma-associated interstitial lung disease (SSc-ILD) via unknown mechanisms. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in Scleroderma has not been explored. This study uses a novel translational platform based on decellularized human lungs to determine whether the scleroderma lung ECM controls fibrocyte development from peripheral blood mononuclear cells. Methods Decellularized scaffolds prepared from healthy and fibrotic Scleroderma lung explants underwent biomechanical evaluation using tensile testing and biochemical analysis using proteomics. Cells from healthy and SSc-ILD subjects were cultured on these scaffolds, and CD45+Pro-ColIα1+ cells meeting criteria for fibrocytes were quantified. The contribution of Netrin-1 to fibrosis was assessed using neutralizing antibodies in this system and via the inhalational administration of bleomycin to Netrin-1+/− mice. Results Compared to control lung scaffold, SSc-ILD lung scaffolds showed aberrant anatomy, enhanced stiffness, and abnormal extracellular matrix composition. Culture of control cells in Scleroderma scaffolds increased Pro-ColIα1+ production, which was stimulated by enhanced stiffness and abnormal ECM composition. SSc-ILD cells demonstrated increased Pro-ColIα1 responsiveness to Scleroderma lung scaffolds, but not enhanced stiffness. Enhanced Netrin-1 expression was seen on CD14lo SSc-ILD cells and antibody mediated Netrin-1 neutralization attenuated CD45+Pro-ColIα1+ detection in all settings. Netrin-1+/− mice were protected from bleomycin induced lung fibrosis and fibrocyte accumulation. Conclusion Factors present in Scleroderma lung matrices regulate fibrocyte accumulation via a Netrin-1-dependent pathway. Netrin-1 regulates bleomycin induced murine pulmonary fibrosis. Netrin-1 might be a novel therapeutic target in SSc-ILD. PMID:26749424

  8. Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.

    Science.gov (United States)

    van den Berg, Sjoerd A A; Heemskerk, Mattijs M; Geerling, Janine J; van Klinken, Jan-Bert; Schaap, Frank G; Bijland, Silvia; Berbée, Jimmy F P; van Harmelen, Vanessa J A; Pronk, Amanda C M; Schreurs, Marijke; Havekes, Louis M; Rensen, Patrick C N; van Dijk, Ko Willems

    2013-08-01

    Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the low APOA5 plasma abundance, we investigated an additional signaling role for APOA5 in high-fat diet (HFD)-induced obesity. Wild-type (WT) and Apoa5(-/-) mice fed a chow diet showed no difference in body weight or 24-h food intake (Apoa5(-/-), 4.5±0.6 g; WT, 4.2±0.5 g), while Apoa5(-/-) mice fed an HFD ate more in 24 h (Apoa5(-/-), 2.8±0.4 g; WT, 2.5±0.3 g, Pcentral regulation of food intake.

  9. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

    Directory of Open Access Journals (Sweden)

    Sonia R Rosner

    Full Text Available Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

  10. GmCLC1 Confers Enhanced Salt Tolerance through Regulating Chloride Accumulation in Soybean

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    Peipei Wei

    2016-07-01

    Full Text Available The family of chloride channel proteins that mediate Cl- transportation play vital roles in plant nutrient supply, cellular action potential and turgor pressure adjustment, stomatal movement, hormone signal recognition and transduction, Cl- homeostasis, and abiotic and biotic stress tolerance. The anionic toxicity, mainly caused by chloride ions (Cl-, on plants under salt stress remains poorly understood. In this work, we investigated the function of soybean Cl-/H+ antiporter GmCLC1 under salt stress in transgenic Arabidopsis thaliana, soybean, and yeast. We found that GmCLC1 enhanced salt tolerance in transgenic A. thaliana by reducing the Cl- accumulation in shoots and hence released the negative impact of salt stress on plant growth. Overexpression of GmCLC1 in the hairy roots of soybean sequestered more Cl- in their roots and transferred less Cl- to their shoots, leading to lower relative electrolyte leakage values in the roots and leaves. When either the soybean GmCLC1 or the yeast chloride transporter gene, GEF1, was transformed into the yeast gef1 mutant, and then treated with different chloride salts (MnCl2, KCl, NaCl, enhanced survival rate was observed. The result indicates that GmCLC1 and GEF1 exerted similar effects on alleviating the stress of diverse chloride salts on the yeast gef1 mutant. Together, this work suggests a protective function of GmCLC1 under Cl- stress.

  11. The Csr System Regulates Escherichia coli Fitness by Controlling Glycogen Accumulation and Energy Levels

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    Manon Morin

    2017-10-01

    Full Text Available In the bacterium Escherichia coli, the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences E. coli fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation.

  12. Genetic regulation of glucoraphanin accumulation in Beneforté® broccoli

    Science.gov (United States)

    Traka, Maria H; Saha, Shikha; Huseby, Stine; Kopriva, Stanislav; Walley, Peter G; Barker, Guy C; Moore, Jonathan; Mero, Gene; den Bosch, Frans; Constant, Howard; Kelly, Leo; Schepers, Hans; Boddupalli, Sekhar; Mithen, Richard F

    2013-01-01

    Diets rich in broccoli (Brassica oleracea var italica) have been associated with maintenance of cardiovascular health and reduction in risk of cancer. These health benefits have been attributed to glucoraphanin that specifically accumulates in broccoli. The development of broccoli with enhanced concentrations of glucoraphanin may deliver greater health benefits. Three high-glucoraphanin F1 broccoli hybrids were developed in independent programmes through genome introgression from the wild species Brassica villosa. Glucoraphanin and other metabolites were quantified in experimental field trials. Global SNP analyses quantified the differential extent of B. villosa introgression The high-glucoraphanin broccoli hybrids contained 2.5–3 times the glucoraphanin content of standard hybrids due to enhanced sulphate assimilation and modifications in sulphur partitioning between sulphur-containing metabolites. All of the high-glucoraphanin hybrids possessed an introgressed B. villosa segment which contained a B. villosa Myb28 allele. Myb28 expression was increased in all of the high-glucoraphanin hybrids. Two high-glucoraphanin hybrids have been commercialised as Beneforté® broccoli. The study illustrates the translation of research on glucosinolate genetics from Arabidopsis to broccoli, the use of wild Brassica species to develop cultivars with potential consumer benefits, and the development of cultivars with contrasting concentrations of glucoraphanin for use in blinded human intervention studies. PMID:23560984

  13. MicroR828 regulates lignin and H2O2 accumulation in sweet potato on wounding.

    Science.gov (United States)

    Lin, Jeng-Shane; Lin, Chih-Ching; Lin, Hsin-Hung; Chen, Yu-Chi; Jeng, Shih-Tong

    2012-10-01

    MicroRNAs (miRNAs) are small noncoding RNAs which post-transcriptionally regulate gene expression by directing mRNA cleavage or translational inhibition. miRNAs play multiple roles in the growth, development and stress responses in plants. However, little is known of the wounding-responsive miRNAs and their regulation. Here, we investigated the expression patterns of microR828 (miR828) on wounding in sweet potato (Ipomoea batatas cv Tainung 57). The expression of miR828 was only detected in leaves, and was induced by wounding rather than by ethylene, hydrogen peroxide (H2O2), methyl jasmonate or nitric oxide (NO). Moreover, cyclic guanosine monophosphate (cGMP) was necessary for miR828 accumulation in leaves on wounding. Two miR828 target candidates, named IbMYB and IbTLD, were obtained by cDNA cloning, and their mRNA cleavage caused by miR828 was confirmed by cleavage site mapping, agro-infiltration and transgenics studies. The reduction in IbMYB and IbTLD expression coincided with the induction of miR828, demonstrating that IbMYB and IbTLD might be miR828 targets. Furthermore, transgenic sweet potato overexpressing miR828 precursor affected lignin and H2O2 contents. These results showed that cGMP could regulate wounding-responsive miR828, which repressed the expression of IbMYB and IbTLD. Subsequently, lignin and H2O2 were accumulated to participate in defense mechanisms. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  14. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding.

    Directory of Open Access Journals (Sweden)

    Janet Chamberlain

    Full Text Available Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1 signaling in the vessel wall would raise arterial blood pressure and promote atheroma.Apoe(-/- and Apoe(-/-/IL-1R1(-/- mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-/IL-R1(-/- mice had a reduced blood pressure and significantly less atheroma than Apoe(-/- mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p < 0.05. This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress.The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man.

  15. Apo-10'-lycopenoic acid, a lycopene 1 metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice

    Science.gov (United States)

    Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 99,10’-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. I...

  16. Coordinated Regulation of Anthocyanin Biosynthesis Genes Confers Varied Phenotypic and Spatial-Temporal Anthocyanin Accumulation in Radish (Raphanus sativus L.

    Directory of Open Access Journals (Sweden)

    Everlyne M'mbone Muleke

    2017-07-01

    Full Text Available Anthocyanins are natural pigments that have important functions in plant growth and development. Radish taproots are rich in anthocyanins which confer different taproot colors and are potentially beneficial to human health. The crop differentially accumulates anthocyanin during various stages of growth, yet molecular mechanisms underlying this differential anthocyanin accumulation remains unknown. In the present study, transcriptome analysis was used to concisely identify putative genes involved in anthocyanin biosynthesis in radish. Spatial-temporal transcript expressions were then profiled in four color variant radish cultivars. From the total transcript sequences obtained through illumina sequencing, 102 assembled unigenes, and 20 candidate genes were identified to be involved in anthocyanin biosynthesis. Fifteen genomic sequences were isolated and sequenced from radish taproot. The length of these sequences was between 900 and 1,579 bp, and the unigene coverage to all of the corresponding cloned sequences was more than 93%. Gene structure analysis revealed that RsF3′H is intronless and anthocyanin biosynthesis genes (ABGs bear asymmetrical exons, except RsSAM. Anthocyanin accumulation showed a gradual increase in the leaf of the red radish and the taproot of colored cultivars during development, with a rapid increase at 30 days after sowing (DAS, and the highest content at maturity. Spatial-temporal transcriptional analysis of 14 genes revealed detectable expressions of 12 ABGs in various tissues at different growth levels. The investigation of anthocyanin accumulation and gene expression in four color variant radish cultivars, at different stages of development, indicated that total anthocyanin correlated with transcript levels of ABGs, particularly RsUFGT, RsF3H, RsANS, RsCHS3 and RsF3′H1. Our results suggest that these candidate genes play key roles in phenotypic and spatial-temporal anthocyanin accumulation in radish through

  17. A progesterone-brown fat axis is involved in regulating fetal growth.

    NARCIS (Netherlands)

    McIlvride, Saraid; Mushtaq, Aleena; Papacleovoulou, Georgia; Hurling, Chloe; Steel, Jennifer; Jansen, Eugène; Abu-Hayyeh, Shadi; Williamson, Catherine

    2017-01-01

    Pregnancy is associated with profound maternal metabolic changes, necessary for the growth and development of the fetus, mediated by reproductive signals acting on metabolic organs. However, the role of brown adipose tissue (BAT) in regulating gestational metabolism is unknown. We show that BAT

  18. Association between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass

    DEFF Research Database (Denmark)

    Nielsen, Anders Rinnov; Hojman, Pernille; Erikstrup, Christian

    2008-01-01

    Objective: IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way...

  19. Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences.

    Directory of Open Access Journals (Sweden)

    Sei Higuchi

    Full Text Available In this study, we examined alterations in the hypothalamic reward system related to high-fat diet (HFD preferences. We previously reported that hypothalamic 2-arachidonoylglycerol (2-AG and glial fibrillary acid protein (GFAP were increased after conditioning to the rewarding properties of a HFD. Here, we hypothesized that increased 2-AG influences the hypothalamic reward system.The conditioned place preference test (CPP test was used to evaluate HFD preferences. Hypothalamic 2-AG was quantified by gas chromatography-mass spectrometry. The expression of GFAP was examined by immunostaining and western blotting.Consumption of a HFD over either 3 or 7 days increased HFD preferences and transiently increased hypothalamic 2-AG levels. HFD consumption over 14 days similarly increased HFD preferences but elicited a long-lasting increase in hypothalamic 2-AG and GFAP levels. The cannabinoid 1 receptor antagonist O-2050 reduced preferences for HFDs after 3, 7, or 14 days of HFD consumption and reduced expression of GFAP after 14 days of HFD consumption. The astrocyte metabolic inhibitor Fluorocitrate blocked HFD preferences after 14 days of HFD consumption.High levels of 2-AG appear to induce HFD preferences, and activate hypothalamic astrocytes via the cannabinoid system. We propose that there may be two distinct stages in the development of HFD preferences. The induction stage involves a transient increase in 2-AG, whereas the maintenance stage involves a long lasting increase in 2-AG levels and activation of astrocytes. Accordingly, hypothalamic 2-AG may influence the development of HFD preferences.

  20. TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

    Directory of Open Access Journals (Sweden)

    Brad J. Niles

    2014-02-01

    Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

  1. Overexpression and RNA interference of TwDXR regulate the accumulation of terpenoid active ingredients in Tripterygium wilfordii.

    Science.gov (United States)

    Zhang, Yifeng; Zhao, Yujun; Wang, Jiadian; Hu, Tianyuan; Tong, Yuru; Zhou, Jiawei; Song, Yadi; Gao, Wei; Huang, Luqi

    2018-02-01

    To examine the putative regulatory role of TwDXR in terpenoid biosynthesis and terpenoid biosynthetic pathway-related gene expression, through overexpression and RNA interference with TwDXR. We obtained 1410 and 454 bp TwDXR-specific fragments to construct overexpression and RNAi vectors. qRT-PCR was used to detect the expression of TwDXR and terpenoid biosynthesis pathway-related genes. The overexpression of TwDXR led to a 285% upregulation and the TwDXR RNAi led to a reduction to 26% of the control (empty vector-transformed cells) levels. However, pathway-related genes displayed different trends. When TwDXR was overexpressed, TwDXS expression decreased by 31% but increased to 198% when TwDXR expression was inhibited. The accumulation of terpenoids was also assayed. In the overexpression group, differences were not significant whereas the contents of triptolide and celastrol in the TwDXR RNAi samples were diminished by 27.3 and 24.0%, respectively. The feedback regulation of gene transcription and the accumulation of terpenoids in terpenoid biosynthesis in Tripterygium wilfordii were verified by TwDXR overexpression and RNAi experiments.

  2. Curcumin and Curcuma longa L. extract ameliorate lipid accumulation through the regulation of the endoplasmic reticulum redox and ER stress.

    Science.gov (United States)

    Lee, Hwa-Young; Kim, Seung-Wook; Lee, Geum-Hwa; Choi, Min-Kyung; Chung, Han-Wool; Lee, Yong-Chul; Kim, Hyung-Ryong; Kwon, Ho Jeong; Chae, Han-Jung

    2017-07-26

    For this study, we examined the effects of curcumin against acute and chronic stress, paying specific attention to ROS. We also aimed to clarify the differences between acute and chronic stress conditions. We investigated the effects of curcumin against acute stress (once/1 day CCl 4 treatment) and chronic-stress (every other day/4week CCl 4 treatment). Compared with acute stress, in which the antioxidant system functioned properly and aspartate transaminase (AST) and ROS production increased, chronic stress increased AST, alanine aminotransferase (ALT), hepatic enzymes, and ROS more significantly, and the antioxidant system became impaired. We also found that ER-originated ROS accumulated in the chronic model, another difference between the two conditions. ER stress was induced consistently, and oxidative intra-ER protein folding status, representatively PDI, was impaired, especially in chronic stress. The PDI-associated client protein hepatic apoB accumulated with the PDI-binding status in chronic stress, and curcumin recovered the altered ER folding status, regulating ER stress and the resultant hepatic dyslipidemia. Throughout this study, curcumin and curcumin-rich Curcuma longa L. extract promoted recovery from CCl 4 -induced hepatic toxicity in both stress conditions. For both stress-associated hepatic dyslipidemia, curcumin and Curcuma longa L. extract might be recommendable to recover liver activity.

  3. Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

    Directory of Open Access Journals (Sweden)

    Yuki Motomura

    2017-06-01

    Full Text Available Many modern people suffer from sleep debt that has accumulated in everyday life but is not subjectively noticed [potential sleep debt (PSD]. Our hypothesis for this study was that resolution of PSD through sleep extension optimizes mood regulation by altering the functional connectivity between the amygdala and prefrontal cortex. Fifteen healthy male participants underwent an experiment consisting of a baseline (BL evaluation followed by two successive interventions, namely, a 9-day sleep extension followed by one night of total sleep deprivation (TSD. Tests performed before and after the interventions included a questionnaire on negative mood and neuroimaging with arterial spin labeling MRI for evaluating regional cerebral blood flow (rCBF and functional connectivity. Negative mood and amygdala rCBF were significantly reduced after sleep extension compared with BL. The amygdala had a significant negative functional connectivity with the medial prefrontal cortex (FCamg–MPFC, and this negative connectivity was greater after sleep extension than at BL. After TSD, these indices reverted to the same level as at BL. An additional path analysis with structural equation modeling showed that the FCamg–MPFC significantly explained the amygdala rCBF and that the amygdala rCBF significantly explained the negative mood. These findings suggest that the use of our sleep extension protocol normalized amygdala activity via negative amygdala–MPFC functional connectivity. The resolution of unnoticed PSD may improve mood by enhancing frontal suppression of hyperactivity in the amygdala caused by PSD accumulating in everyday life.

  4. Multiple R2R3-MYB transcription factors involved in the regulation of anthocyanin accumulation in peach flower

    Directory of Open Access Journals (Sweden)

    Hui Zhou

    2016-10-01

    Full Text Available Anthocyanin accumulation is responsible for flower coloration in peach. Here, we report the identification and functional characterization of eight flavonoid-related R2R3-MYB transcription factors, designated PpMYB10.2, PpMYB9, PpMYBPA1, Peace, PpMYB17, PpMYB18, PpMYB19 and PpMYB20, respectively, in peach flower transcriptome. PpMYB10.2 and PpMYB9 are able to activate transcription of anthocyanin biosynthetic genes, whilst PpMYBPA1 and Peace have a strong activation on the promoters of proanthocyanin (PA biosynthetic genes. PpMYB17-20 show a strong repressive effect on transcription of flavonoid pathway genes such as DFR. These results indicate that anthocyanin accumulation in peach flower is coordinately regulated by a set of R2R3-MYB genes. In addition, PpMYB9 and PpMYB10.2 are closely related but separated into two groups, designated MYB9 and MYB10, respectively. PpMYB9 shows a strong activation on the PpUGT78A2 promoter, but with no effect on the promoter of PpUGT78B (commonly called PpUFGT in previous studies. In contrast, PpMYB10.2 is able to activate the PpUFGT promoter, but not for the PpUGT78A2 promoter. Unlike the MYB10 gene that is universally present in plants, the MYB9 gene is lost in most dicot species. Therefore, the PpMYB9 gene represents a novel group of anthocyanin-related MYB activators, which may have diverged in function from the MYB10 genes. Our study will aid in understanding the complex mechanism regulating floral pigmentation in peach and functional divergence of the R2R3-MYB gene family in plants.

  5. Allosteric regulation of 6-phosphofructo-1-kinase activity of fat body and flight muscle from the bloodsucking bug Rhodnius prolixus

    Directory of Open Access Journals (Sweden)

    Gutemberg G. Alves

    2007-03-01

    Full Text Available 6-phosphofructo-1-kinase (phosphofructokinase; PFK activity from Rhodnius prolixus, a haematophagous insect which is usually a poor flyer, was measured and compared in two metabolically active tissues - flight muscle and fat body. The activity of this important regulatory glycolytic enzyme was much more pronounced in muscle (15.1 ± 1.4 U/mg than in fat body extracts (3.6±0.4 U/mg, although the latter presented higher levels of enzyme per protein content, as measured by western-blotting. Muscle extracts are more responsible than fat body to ATP and fructose 6-phosphate, both substrates of PFK. Allosteric regulation exerted by different effectors such as ADP, AMP and fructose 2,6-phosphate presented a singular pattern for each tissue. Optimal pH (8.0-8.5 and sensitivity to pH variation was very similar, and citrate was unable to inhibit PFK activity in both extracts. Our results suggest the existence of a particular PFK activity for each tissue, with regulatory patterns that are consistent with their physiological roles.A atividade da fosfofrutocinase (PFK de Rodnius prolixus, um inseto hematófago, o qual vôa somente pequenas distâncias, foi medida e comparada em dois tecidos metabolicamente ativos - músculo de asa e corpo gorduroso. A atividade desta importante enzima glicolítica regulatória foi muito mais pronunciada em músculo de asa (15,1 ±1,4 U/mg do que em extrato de corpo gorduroso (3,6 ±0,4 U/mg embora este último tenha apresentado níveis mais altos da enzima por quantidade de proteína, como medido por western-blotting. Extratos de músculo foram mais responsivos do que corpo gorduroso para ATP e frutose-6-fosfato, ambos substratos da PFK. A regulação alostérica exercida por diferentes efetores tais como ADP, AMP, frutose-2,6-bisfosfato apresentou um padrão singular para cada tecido. O pH ótimo (8,0-8,5 e a sensibilidade a variações de pH, foram muito similares e o citrato foi incapaz de inibir a atividade da PFK em

  6. Alleviation of harmful effect in stillage reflux in food waste ethanol fermentation based on metabolic and side-product accumulation regulation.

    Science.gov (United States)

    Ma, Hongzhi; Yang, Jian; Jia, Yan; Wang, Qunhui; Ma, Xiaoyu; Sonomoto, Kenji

    2016-10-01

    Stillage reflux fermentation in food waste ethanol fermentation could reduce sewage discharge but exert a harmful effect because of side-product accumulation. In this study, regulation methods based on metabolic regulation and side-product alleviation were conducted. Result demonstrated that controlling the proper oxidation-reduction potential value (-150mV to -250mV) could reduce the harmful effect, improve ethanol yield by 21%, and reduce fermentation time by 20%. The methods of adding calcium carbonate to adjust the accumulated lactic acid showed that ethanol yield increased by 17.3%, and fermentation time decreased by 20%. The accumulated glyceal also shows that these two methods can reduce the harmful effect. Fermentation time lasted for seven times without effect, and metabolic regulation had a better effect than side-product regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle

    OpenAIRE

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid conten...

  8. The role of environmental factors in regulating the development of cartilaginous grafts engineered using osteoarthritic human infrapatellar fat pad-derived stem cells.

    Science.gov (United States)

    Liu, Yurong; Buckley, Conor T; Downey, Richard; Mulhall, Kevin J; Kelly, Daniel J

    2012-08-01

    Engineering functional cartilaginous grafts using stem cells isolated from osteoarthritic human tissue is of fundamental importance if autologous tissue engineering strategies are to be used in the treatment of diseased articular cartilage. It has previously been demonstrated that human infrapatellar fat pad (IFP)-derived stem cells undergo chondrogenesis in pellet culture; however, the ability of such cells to generate functional cartilaginous grafts has not been adequately addressed. The objective of this study was to explore how environmental conditions regulate the functional development of cartilaginous constructs engineered using diseased human IFP-derived stem cells (FPSCs). FPSCs were observed to display a diminished chondrogenic potential upon encapsulation in a three-dimensional hydrogel compared with pellet culture, synthesizing significantly lower levels of glycosaminoglycan and collagen on a per cell basis. To engineer more functional cartilaginous grafts, we next explored whether additional biochemical and biophysical stimulations would enhance chondrogenesis within the hydrogels. Serum stimulation was observed to partially recover the diminished chondrogenic potential within hydrogel culture. Over 42 days, stem cells that had first been expanded in a low-oxygen environment proliferated extensively on the outer surface of the hydrogel in response to serum stimulation, assembling a dense type II collagen-positive cartilaginous tissue resembling that formed in pellet culture. The application of hydrostatic pressure did not further enhance extracellular matrix synthesis within the hydrogels, but did appear to alter the spatial accumulation of extracellular matrix leading to the formation of a more compact tissue with superior mechanically functionality. Further work is required in order to recapitulate the environmental conditions present during pellet culture within scaffolds or hydrogels in order to engineer more functional cartilaginous grafts using

  9. Reduction of abdominal fat accumulation in rats by 8-week ingestion of a newly developed sweetener made from high fructose corn syrup.

    Science.gov (United States)

    Iida, Tetsuo; Yamada, Takako; Hayashi, Noriko; Okuma, Kazuhiro; Izumori, Ken; Ishii, Reika; Matsuo, Tatsuhiro

    2013-06-01

    Many studies have shown that ingestion of high-fructose corn syrup (HFCS) may cause an increase in body weight and abdominal fat. We recently developed a new sweetener containing rare sugars (rare sugar syrup; RSS) by slight isomerization of HFCS. Here, the functional effects of RSS on body weight and abdominal fat, and biochemical parameters in Wistar rats were examined. Rats (n=30) were randomly divided into three groups and maintained for 8-weeks on starch, starch+HFCS (50:50), and starch+RSS (50:50) diets. Rats in the Starch and HFCS groups gained significantly more body weight and abdominal fat than the RSS group. Fasting serum insulin in the RSS group was significantly lower than in the Starch and HFCS groups, although serum glucose in the HFCS and RSS groups was significantly lower than that in the Starch group. Thus, the substitution of HFCS with RSS prevents obesity induced by the consumption of HFCS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Netrin-1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin-Induced Pulmonary Fibrosis.

    Science.gov (United States)

    Sun, Huanxing; Zhu, Yangyang; Pan, Hongyi; Chen, Xiaosong; Balestrini, Jenna L; Lam, TuKiet T; Kanyo, Jean E; Eichmann, Anne; Gulati, Mridu; Fares, Wassim H; Bai, Hanwen; Feghali-Bostwick, Carol A; Gan, Ye; Peng, Xueyan; Moore, Meagan W; White, Eric S; Sava, Parid; Gonzalez, Anjelica L; Cheng, Yuwei; Niklason, Laura E; Herzog, Erica L

    2016-05-01

    protected against bleomycin-induced lung fibrosis and fibrocyte accumulation. Factors present in the lung matrices of patients with scleroderma regulate fibrocyte accumulation via a netrin-1-dependent pathway. Netrin-1 regulates bleomycin-induced pulmonary fibrosis in mice. Netrin-1 might be a novel therapeutic target in SSc-related ILD. © 2016, American College of Rheumatology.

  11. Some aspects of the regulation for waste management with special emphasize on the batteries and accumulators and waste batteries and accumulators in Republic of Macedonia

    OpenAIRE

    Andonov, Marko; Miseva, Kristina

    2012-01-01

    The recent development of law in the field of environment undoubtedly experiences expansion. Republic of Macedonia as a state candidate for full membership of EU, in the recent several years makes significant efforts for harmonization of its legal regulation in the field of environment with the legal regulation of the Union. The Law on Waste Management has a special place in the subject problem. By passing and harmonization of the laws and subordinate regulation with acquies and according to ...

  12. A high throughput live transparent animal bioassay to identify non-toxic small molecules or genes that regulate vertebrate fat metabolism for obesity drug development

    Directory of Open Access Journals (Sweden)

    Woollett Laura A

    2008-08-01

    142 antagonists may be effective non-toxic anti-obesity therapeutics. Conclusion Owing to the apparently high level of evolutionary conservation of signal transduction pathways regulating lipid metabolism, the zebrafish can be useful for identifying non-toxic small molecules or pharmacological target gene products for developing molecular therapeutics for treating clinical obesity. Our results support the promising potential in applying NAD or resveratrol where the underlying target protein likely involves Sirtuin family member proteins. Furthermore data supports future studies focused on determining whether there is a high concentration window for resveratrol that is effective and non-toxic in high fat obesity murine models.

  13. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

    Science.gov (United States)

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats.

  14. Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation

    DEFF Research Database (Denmark)

    Axelsen, Lene N; Lademann, Jacob B; Petersen, Jørgen S

    2010-01-01

    Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model....... FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed...

  15. Ablation of TRIP-Br2, a novel regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance

    Science.gov (United States)

    Liew, Chong Wee; Boucher, Jeremie; Cheong, Jit Kong; Vernochet, Cecile; Koh, Ho-Jin; Mallol, Cristina; Townsend, Kristy; Langin, Dominique; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Hellerstein, Marc K; Farmer, Stephen R; Goodyear, Laurie; Doria, Alessandro; Blüher, Matthias; Hsu, Stephen I-Hong; Kulkarni, Rohit N

    2012-01-01

    SUMMARY Obesity develops due to altered energy homeostasis favoring fat storage. Here we describe a novel transcription co-regulator for adiposity and energy metabolism, TRIP-Br2 (also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of the knockout (KO) mice exhibited greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The KOs also exhibit higher energy expenditure due to increased adipocyte thermogenesis and oxidative metabolism by up-regulating key enzymes in respective processes. Our data show for the first time that a cell cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data together with the observation that TRIP-BR2 expression is selectively elevated in visceral fat in obese humans suggests that this transcriptional co-regulator is a novel therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia. PMID:23291629

  16. Foliar Abscisic Acid-To-Ethylene Accumulation and Response Regulate Shoot Growth Sensitivity to Mild Drought in Wheat

    Science.gov (United States)

    Valluru, Ravi; Davies, William J.; Reynolds, Matthew P.; Dodd, Ian C.

    2016-01-01

    Although, plant hormones play an important role in adjusting growth in response to environmental perturbation, the relative contributions of abscisic acid (ABA) and ethylene remain elusive. Using six spring wheat genotypes differing for stress tolerance, we show that young seedlings of the drought-tolerant (DT) group maintained or increased shoot dry weight (SDW) while the drought-susceptible (DS) group decreased SDW in response to mild drought. Both the DT and DS groups increased endogenous ABA and ethylene concentrations under mild drought compared to control. The DT and DS groups exhibited different SDW response trends, whereby the DS group decreased while the DT group increased SDW, to increased concentrations of ABA and ethylene under mild drought, although both groups decreased ABA/ethylene ratio under mild drought albeit at different levels. We concluded that SDW of the DT and DS groups might be distinctly regulated by specific ABA:ethylene ratio. Further, a foliar-spray of low concentrations (0.1 μM) of ABA increased shoot relative growth rate (RGR) in the DS group while ACC (1-aminocyclopropane-1-carboxylic acid, ethylene precursor) spray increased RGR in both groups compared to control. Furthermore, the DT group accumulated a significantly higher galactose while a significantly lower maltose in the shoot compared to the DS group. Taken all together, these results suggest an impact of ABA, ethylene, and ABA:ethylene ratio on SDW of wheat seedlings that may partly underlie a genotypic variability of different shoot growth sensitivities to drought among crop species under field conditions. We propose that phenotyping based on hormone accumulation, response and hormonal ratio would be a viable, rapid, and an early–stage selection tool aiding genotype selection for stress tolerance. PMID:27148292

  17. The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice.

    Directory of Open Access Journals (Sweden)

    Xue Gao

    2010-11-01

    Full Text Available FTO (fat mass and obesity associated was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal α-helical domain and an N-terminal double-strand β-helix domain which is conserved in Fe(II and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth.

  18. The role of leptin and other hormones related to bone metabolism and appetite-regulation as determinants of gain in body fat and fat-free mass in 8-11 year old children

    DEFF Research Database (Denmark)

    Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni

    2015-01-01

    Background: Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. Objectives: We examined if baseline fasting levels of ghrelin, adiponectin, leptin, insulin, insulin......-like growth factor I (IGF-1), osteocalcin and intact parathyroid hormone (iPTH) were associated with body composition cross-sectionally and longitudinally in 633 8-11-year-olds. Design: Data on hormones and body composition by Dual-energy X-ray absorptiometry from OPUS School Meal Study were used. We looked...... at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (three and six months) in FMI or FFMI using models with hormones individually or combined. Results: Cross-sectionally, baseline leptin was positively associated with FMI in girls (0...

  19. Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Liew, Chong Wee; Boucher, Jeremie; Cheong, Jit Kong; Vernochet, Cecile; Koh, Ho-Jin; Mallol, Cristina; Townsend, Kristy; Langin, Dominique; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Hellerstein, Marc K; Farmer, Stephen R; Goodyear, Laurie; Doria, Alessandro; Blüher, Matthias; Hsu, Stephen I-Hong; Kulkarni, Rohit N

    2013-02-01

    Obesity develops as a result of altered energy homeostasis favoring fat storage. Here we describe a new transcription co-regulator for adiposity and energy metabolism, SERTA domain containing 2 (TRIP-Br2, also called SERTAD2). TRIP-Br2-null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of these knockout mice showed greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and β3-adrenergic (Adrb3) receptors. The knockout mice also have higher energy expenditure because of increased adipocyte thermogenesis and oxidative metabolism caused by upregulating key enzymes in their respective processes. Our data show that a cell-cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data, together with the observation that TRIP-Br2 expression is selectively elevated in visceral fat in obese humans, suggests that this transcriptional co-regulator is a new therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia.

  20. Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation

    Science.gov (United States)

    Leung, Vivien; Chiu, Ya-Lin; Kotler, Donald P.; Albu, Jeanine; Zhu, Yuan-Shan; Ham, Kirsis; Engelson, Ellen S.; Hammad, Hoda; Christos, Paul; Donovan, Daniel S.; Ginsberg, Henry N.; Glesby, Marshall J.

    2016-01-01

    Background/Objective In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of recombinant human growth hormone (rhGH) and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers. Methods 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n = 63) and 12 (n = 46-48) were assessed for adiponectin, C-reactive protein (CRP), homocysteine, interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator (tPA) antigen. Results Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH alone arm. There were no significant changes in the other biomarkers amongst the different treatment groups. Discussion In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with combination rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT. PMID:27077672

  1. Post-Transcriptional Regulation Prevents Accumulation of Glutathione Reductase Protein and Activity in the Bundle Sheath Cells of Maize1

    Science.gov (United States)

    Pastori, Gabriela M.; Mullineaux, Philip M.; Foyer, Christine H.

    2000-01-01

    Glutathione reductase (GR; EC 1.6.4.2) activity was assayed in bundle sheath and mesophyll cells of maize (Zea mays L. var H99) from plants grown at 20°C, 18°C, and 15°C. The purity of each fraction was determined by measuring the associated activity of the compartment-specific marker enzymes, Rubisco and phosphoenolpyruvate carboxylase, respectively. GR activity and the abundance of GR protein and mRNA increased in plants grown at 15°C and 18°C compared with those grown at 20°C. In all cases GR activity was found only in mesophyll fractions of the leaves, with no GR activity being detectable in bundle sheath extracts. Immunogold labeling with GR-specific antibodies showed that the GR protein was exclusively localized in the mesophyll cells of leaves at all growth temperatures, whereas GR transcripts (as determined by in situ hybridization techniques) were observed in both cell types. These results indicate that post-transcriptional regulation prevents GR accumulation in the bundle sheath cells of maize leaves. The resulting limitation on the capacity for regeneration of reduced glutathione in this compartment may contribute to the extreme chilling sensitivity of maize leaves. PMID:10712529

  2. Abscisic acid-regulated protein degradation causes osmotic stress-induced accumulation of branched-chain amino acids in Arabidopsis thaliana.

    Science.gov (United States)

    Huang, Tengfang; Jander, Georg

    2017-10-01

    Whereas proline accumulates through de novo biosynthesis in plants subjected to osmotic stress, leucine, isoleucine, and valine accumulation in drought-stressed Arabidopsis thaliana is caused by abscisic acid-regulated protein degradation. In response to several kinds of abiotic stress, plants greatly increase their accumulation of free amino acids. Although stress-induced proline increases have been studied the most extensively, the fold-increase of other amino acids, in particular branched-chain amino acids (BCAAs; leucine, isoleucine, and valine), is often higher than that of proline. In Arabidopsis thaliana (Arabidopsis), BCAAs accumulate in response to drought, salt, mannitol, polyethylene glycol, herbicide treatment, and nitrogen starvation. Plants that are deficient in abscisic acid signaling accumulate lower amounts of BCAAs, but not proline and most other amino acids. Previous bioinformatic studies had suggested that amino acid synthesis, rather than protein degradation, is responsible for the observed BCAA increase in osmotically stressed Arabidopsis. However, whereas treatment with the protease inhibitor MG132 decreased drought-induced BCAA accumulation, inhibition of BCAA biosynthesis with the acetolactate synthase inhibitors chlorsulfuron and imazapyr did not. Additionally, overexpression of BRANCHED-CHAIN AMINO ACID TRANSFERASE2 (BCAT2), which is upregulated in response to osmotic stress and functions in BCAA degradation, decreased drought-induced BCAA accumulation. Together, these results demonstrate that BCAA accumulation in osmotically stressed Arabidopsis is primarily the result of protein degradation. After relief of the osmotic stress, BCAA homeostasis is restored over time by amino acid degradation involving BCAT2. Thus, drought-induced BCAA accumulation is different from that of proline, which is accumulated due to de novo synthesis in an abscisic acid-independent manner and remains elevated for a more prolonged period of time after removal of

  3. Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity

    OpenAIRE

    Kim, Jongwan; Yun, Eun-Young; Quan, Fu-Shi; Park, Seung-Won; Goo, Tae-Won

    2017-01-01

    The α-glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Result...

  4. Sida rhomboidea. Roxb leaf extract down-regulates expression of PPARγ2 and leptin genes in high fat diet fed C57BL/6J Mice and retards in vitro 3T3L1 pre-adipocyte differentiation.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Ramani, Umed V; Devkar, Ranjitsinh V; Ramachandran, A V

    2011-01-01

    Sida rhomboidea. Roxb leaf extract (SRLE) is being used by the populace of North-East India to alleviate symptoms of diabetes and obesity. We have previously reported its hypolipidemic and anti-diabetic properties. In this study, we report the effect of SRLE on (i) in vivo modulation of genes controlling high fat diet (HFD) induced obesity and (ii) in vitro 3T3L1 pre-adipocyte differentiation and leptin release. Supplementation with SRLE significantly prevented HFD induced increment in bodyweight, plasma lipids and leptin, visceral adiposity and adipocyte hypertrophy. Also, SRLE supplementation reduced food intake, down regulated PPARγ2, SREBP1c, FAS and LEP expressions and up-regulated CPT-1 in epididymal adipose tissue compared to obese mice. In vitro adipogenesis of 3T3L1 pre-adipocytes was significantly retarded in the presence of SRLE extract. Also decreased triglyceride accumulation, leptin release and glyceraldehyde-3-Phosphate dehydrogenase activity along with higher glycerol release without significant alteration of viability of 3T3L1 pre-adipocytes, was recorded. Our findings suggest that prevention of HFD induced visceral adiposity is primarily by down regulation of PPARγ2 and leptin gene expression coupled with attenuation of food intake in C57BL/6J mice. SRLE induced prevention of pre-adipocytes differentiation, and leptin release further substantiated these findings and scientifically validates the potential application of SRLE as a therapeutic agent against obesity.

  5. Identification and Characterization of Oleaginous Yeast Isolated from Kefir and Its Ability to Accumulate Intracellular Fats in Deproteinated Potato Wastewater with Different Carbon Sources

    Science.gov (United States)

    Kieliszek, Marek; Jermacz, Karolina; Błażejak, Stanisław

    2017-01-01

    The search for efficient oleaginous microorganisms, which can be an alternative to fossil fuels and biofuels obtained from oilseed crops, has been going on for many years. The suitability of microorganisms in this regard is determined by their ability to biosynthesize lipids with preferred fatty acid profile along with the concurrent utilization of energy-rich industrial waste. In this study, we isolated, characterized, and identified kefir yeast strains using molecular biology techniques. The yeast isolates identified were Candida inconspicua, Debaryomyces hansenii, Kluyveromyces marxianus, Kazachstania unispora, and Zygotorulaspora florentina. We showed that deproteinated potato wastewater, a starch processing industry waste, supplemented with various carbon sources, including lactose and glycerol, is a suitable medium for the growth of yeast, which allows an accumulation of over 20% of lipid substances in its cells. Fatty acid composition primarily depended on the yeast strain and the carbon source used, and, based on our results, most of the strains met the criteria required for the production of biodiesel. In particular, this concerns a significant share of saturated fatty acids, such as C16:0 and C18:0, and unsaturated fatty acids, such as C18:1 and C18:2. The highest efficiency in lipid biosynthesis exceeded 6.3 g L−1. Kazachstania unispora was able to accumulate the high amount of palmitoleic acid. PMID:29098157

  6. Identification and Characterization of Oleaginous Yeast Isolated from Kefir and Its Ability to Accumulate Intracellular Fats in Deproteinated Potato Wastewater with Different Carbon Sources

    Directory of Open Access Journals (Sweden)

    Iwona Gientka

    2017-01-01

    Full Text Available The search for efficient oleaginous microorganisms, which can be an alternative to fossil fuels and biofuels obtained from oilseed crops, has been going on for many years. The suitability of microorganisms in this regard is determined by their ability to biosynthesize lipids with preferred fatty acid profile along with the concurrent utilization of energy-rich industrial waste. In this study, we isolated, characterized, and identified kefir yeast strains using molecular biology techniques. The yeast isolates identified were Candida inconspicua, Debaryomyces hansenii, Kluyveromyces marxianus, Kazachstania unispora, and Zygotorulaspora florentina. We showed that deproteinated potato wastewater, a starch processing industry waste, supplemented with various carbon sources, including lactose and glycerol, is a suitable medium for the growth of yeast, which allows an accumulation of over 20% of lipid substances in its cells. Fatty acid composition primarily depended on the yeast strain and the carbon source used, and, based on our results, most of the strains met the criteria required for the production of biodiesel. In particular, this concerns a significant share of saturated fatty acids, such as C16:0 and C18:0, and unsaturated fatty acids, such as C18:1 and C18:2. The highest efficiency in lipid biosynthesis exceeded 6.3 g L−1. Kazachstania unispora was able to accumulate the high amount of palmitoleic acid.

  7. Identification and Characterization of Oleaginous Yeast Isolated from Kefir and Its Ability to Accumulate Intracellular Fats in Deproteinated Potato Wastewater with Different Carbon Sources.

    Science.gov (United States)

    Gientka, Iwona; Kieliszek, Marek; Jermacz, Karolina; Błażejak, Stanisław

    2017-01-01

    The search for efficient oleaginous microorganisms, which can be an alternative to fossil fuels and biofuels obtained from oilseed crops, has been going on for many years. The suitability of microorganisms in this regard is determined by their ability to biosynthesize lipids with preferred fatty acid profile along with the concurrent utilization of energy-rich industrial waste. In this study, we isolated, characterized, and identified kefir yeast strains using molecular biology techniques. The yeast isolates identified were Candida inconspicua , Debaryomyces hansenii , Kluyveromyces marxianus , Kazachstania unispora , and Zygotorulaspora florentina . We showed that deproteinated potato wastewater, a starch processing industry waste, supplemented with various carbon sources, including lactose and glycerol, is a suitable medium for the growth of yeast, which allows an accumulation of over 20% of lipid substances in its cells. Fatty acid composition primarily depended on the yeast strain and the carbon source used, and, based on our results, most of the strains met the criteria required for the production of biodiesel. In particular, this concerns a significant share of saturated fatty acids, such as C16:0 and C18:0, and unsaturated fatty acids, such as C18:1 and C18:2. The highest efficiency in lipid biosynthesis exceeded 6.3 g L -1 . Kazachstania unispora was able to accumulate the high amount of palmitoleic acid.

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

    Science.gov (United States)

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

    2016-01-01

    Background Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food. Objective The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis. Design Rats were divided into four groups (n=6 per group) after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control) with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w.)/day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50) with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks. Results We found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG), and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and β-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase. Conclusions These results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis. PMID:26822962

  9. The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance) and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men.

    Science.gov (United States)

    Fujibayashi, Kazutoshi; Gunji, Toshiaki; Yokokawa, Hirohide; Naito, Toshio; Sasabe, Noriko; Okumura, Mitsue; Iijima, Kimiko; Shibuya, Katsuhiko; Hisaoka, Teruhiko; Fukuda, Hiroshi

    2016-01-01

    Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance) and hepatic steatosis (HS) or visceral fat accumulation (VFA) have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA. The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan's metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+) or absence (-) of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups. Among the participants, 521, 55, 24, and 15 were classified as HS(-)/VFA(-), HS(-)/VFA(+), HS(+)/VFA(-), and HS(+)/VFA(+), respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05). On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01). It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders. Further large-scale longitudinal studies are

  10. The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Fujibayashi

    Full Text Available Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance and hepatic steatosis (HS or visceral fat accumulation (VFA have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA.The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan's metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+ or absence (- of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups.Among the participants, 521, 55, 24, and 15 were classified as HS(-/VFA(-, HS(-/VFA(+, HS(+/VFA(-, and HS(+/VFA(+, respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05. On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01.It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders. Further large-scale longitudinal studies

  11. 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

  12. G/sub o/ protein of fat cells: role in hormonal regulation of agonist-stimulated phosphatidyl inositol breakdown

    International Nuclear Information System (INIS)

    Rapiejko, P.J.; Northup, J.K.; Malbon, C.C.

    1986-01-01

    Incubating rat fat cell membranes in the presence of [ 32 P]NAD + and pertussis toxin (PT) results in the ADP-ribosylation of two peptides (M/sub r/ = 41,000 and 40,000). The 41,000-M/sub r/ peptide is the inhibitory G-protein of adenylate cyclase (G/sub i/). The 40,000-M/sub r/ peptide radiolabeled in the presence of [ 32 P]NAD + and PT has been purified from rabbit heart and bovine brain, but has not been identified uniformly in membranes of fat cells. Two rabbit polyclonal antisera raised against the alpha-subunit of bovine brain G/sub o/ were used to probe the nature of the 40,000-M/sub r/ peptide in rat fat cell membranes that had been separated by gel electrophoresis in the presence of sodium dodecyl sulfate and transferred electrophoretically to nitrocellulose. Both antisera specific for the alpha-subunit of G/sub o/ recognized the M/sub r/ = 40,000 peptide of fat cells that is ADP-ribosylated in the presence of PT. PT treatment of rat fat cells blocks epinephrine-stimulated inositol 1,4,5 trisphosphate (IP 3 ) generation. The inhibition of IP 3 generation by PT suggests a role for either G/sub i/ or G/sub o/ in receptor-mediated phosphatidyl inositol breakdown in the rat fat cell

  13. Global Picture of Protein Regulation in Response to Dibutyl Phthalate (DBP) Stress of Two Brassica parachinensis Cultivars Differing in DBP Accumulation.

    Science.gov (United States)

    Zhao, Hai-Ming; Huang, He-Biao; Du, Huan; Xiang, Lei; Mo, Ce-Hui; Li, Yan-Wen; Cai, Quan-Ying; Li, Hui; Liu, Jie-Sheng; Zhou, Dong-Mei; Wong, Ming-Hung

    2018-05-09

    iTRAQ analysis was used to map the proteomes of two Brassica parachinensis cultivars that differed in dibutyl phthalate (DBP) accumulation. A total of 5699 proteins were identified to obtain 152 differentially regulated proteins, of which 64 and 48 were specific to a high- and a low-DBP-accumulation cultivar, respectively. Genotype-specific biological processes were involved in coping with DBP stress, accounting for the variation in DBP tolerance and accumulation. Formation of high DBP accumulation in B. parachinensis might attribute to the more effective regulation of protein expression in physiology and metabolism, including (a) enhanced cell wall biosynthesis and modification, (b) better maintenance of photosynthesis and energy balance, (c) greatly improved total capacity for antioxidation and detoxification, and (d) enhanced cellular transport and signal transduction. Our novel findings contribute to a global picture of DBP-induced alterations of protein profiles in crops and provide valuable information for the development of molecular-assisted breeds of low-accumulation cultivars.

  14. dSir2 in the Adult Fat Body, but Not in Muscles, Regulates Life Span in a Diet-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Kushal Kr. Banerjee

    2012-12-01

    Full Text Available Sir2, an evolutionarily conserved NAD+-dependent deacetylase, has been implicated as a key factor in mediating organismal life span. However, recent contradictory findings have brought into question the role of Sir2 and its orthologs in regulating organismal longevity. In this study, we report that Drosophila Sir2 (dSir2 in the adult fat body regulates longevity in a diet-dependent manner. We used inducible Gal4 drivers to knock down and overexpress dSir2 in a tissue-specific manner. A diet-dependent life span phenotype of dSir2 perturbations (both knockdown and overexpression in the fat body, but not muscles, negates the effects of background genetic mutations. In addition to providing clarity to the field, our study contrasts the ability of dSir2 in two metabolic tissues to affect longevity. We also show that dSir2 knockdown abrogates fat-body dFOXO-dependent life span extension. This report highlights the importance of the interplay between genetic factors and dietary inputs in determining organismal life spans.

  15. Dlk1/FA1 Is a Novel Endocrine Regulator of Bone and Fat Mass and Its Serum Level Is Modulated By Growth Hormone

    DEFF Research Database (Denmark)

    Abdallah, B.M.; Ding, M.; Jensen, C.H.

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. FA1 (fetal antigen 1) is the soluble form of dlk1 (delta like 1), which is a member of the Notch-Delta family. We have previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1-mice) using the hydrodynamic-based gene transfer procedure (HGTP). We found that increased serum FA1 levels led to a significant reduction in total body weight......, fat mass and bone mass in a dose-dependent manner. Reduced bone mass in FA1-mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58% and 72% respectively. Since FA1 is co-localized with growth hormone (GH) in the pituitary gland, we explored the possible...

  16. Dlk1/FA1 is a novel endocrine regulator of bone and fat mass and its serum level is modulated by growth hormone

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ding, Ming; Jensen, Charlotte H

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. Fetal antigen 1 (FA1) is the soluble form of dlk1 (delta-like 1), which is a member of the Notch-Delta family. We previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1 mice) using the hydrodynamic-based gene transfer procedure. We found that increased serum FA1 levels led to a significant reduction in total body weight, fat...... mass, and bone mass in a dose-dependent manner. Reduced bone mass in FA1 mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58 and 72%, respectively. Because FA1 is colocalized with GH in the pituitary gland, we explored the possible modulation of serum FA1...

  17. Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages.

    Directory of Open Access Journals (Sweden)

    Jaimie Hoh Kam

    Full Text Available BACKGROUND: Amyloid beta (Aβ accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which Aβ is a key constituent. Aβ activates the complement cascade and its deposition is associated with activated macrophages. So far, little is known about the quantitative measurements of Aβ accumulation and definitions of its relative sites of ocular deposition in the normal ageing mouse. METHODOLOGY/PRINCIPAL FINDINGS: We have traced Aβ accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While Aβ is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of Aβ on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in Aβ showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including Aβ, however, their increasing numbers fail to stop Aβ accumulation. CONCLUSIONS: Increasing Aβ deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of Aβ may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The

  18. Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation

    DEFF Research Database (Denmark)

    Tremaroli, Valentina; Karlsson, Fredrik; Werling, Malin

    2015-01-01

    Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass...... or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls....... By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut...

  19. Toll-like receptor 4 mediates fat, sugar, and umami taste preference and food intake and body weight regulation.

    Science.gov (United States)

    Camandola, Simonetta; Mattson, Mark P

    2017-07-01

    Immune and inflammatory pathways play important roles in the pathogenesis of metabolic disorders. This study investigated the role of toll-like receptor 4 (TLR4) in orosensory detection of dietary lipids and sugars. Taste preferences of TLR4 knockout (KO) and wild-type (WT) male mice under a standard and a high-fat, high-sugar diet were assessed with two-bottle tests. Gene expression of taste signaling molecules was analyzed in the tongue epithelium. The role of TLR4 in food intake and weight gain was investigated in TLR4 KO and WT mice fed a high-fat and high-sugar diet for 12 weeks. Compared to WT mice, TLR4 KO mice showed reduced preference for lipids, sugars, and umami in a two-bottle preference test. The altered taste perception was associated with decreased levels of key taste regulatory molecules in the tongue epithelium. TLR4 KO mice on a high-fat and high-sugar diet consumed less food and drink, resulting in diminished weight gain. TLR4 signaling promotes ingestion of sugar and fat by a mechanism involving increased preference for such obesogenic foods. © 2017 The Obesity Society.

  20. Regulation of myofibrillar accumulation in chick muscle cultures - Evidence for the involvement of calcium and lysosomes in non-uniform turnover of contractile proteins

    Science.gov (United States)

    Silver, Geri; Etlinger, Joseph D.

    1985-01-01

    The effects of calcium on the synthesis and the degradation of individual myofibrillar proteins were investigated using primary chick-leg skeletal muscle cultures labeled with S-35-methionine (for protein accumulation experiments) or Ca(2+)-45 (for calcium efflux experiments). It was found that the turnover of individual contractile proteins is regulated nonuniformly by a calcium-dependent mechanism involving lysosomes. The results also indicate that contractile proteins are released from the myofibril before their breakdown to amino acids.

  1. Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

    International Nuclear Information System (INIS)

    Liu, Wei-Xin; Wang, Ting; Zhou, Feng; Wang, Ying; Xing, Jun-Wei; Zhang, Shen; Gu, Shou-Zhi; Sang, Li-Xuan; Dai, Cong; Wang, Hai-Lan

    2015-01-01

    Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

  2. Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wei-Xin, E-mail: weixinliu@yahoo.com [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Wang, Ting; Zhou, Feng; Wang, Ying; Xing, Jun-Wei; Zhang, Shen [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Gu, Shou-Zhi [Department of Anatomy, Seirei Christopher College, Hamamatsu 433-8558 (Japan); Sang, Li-Xuan [Department of Cadre Ward II, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Dai, Cong [Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning (China); Wang, Hai-Lan [Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, Guangdong (China)

    2015-04-10

    Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

  3. Hemopressins and other hemoglobin-derived peptides in mouse brain: Comparison between brain, blood, and heart peptidome and regulation in Cpefat/fat mice

    Science.gov (United States)

    Gelman, Julia S.; Sironi, Juan; Castro, Leandro M.; Ferro, Emer S.; Fricker, Lloyd D.

    2010-01-01

    Many hemoglobin-derived peptides are present in mouse brain, and several of these have bioactive properties including the hemopressins, a related series of peptides that bind to cannabinoid CB1 receptors. Although hemoglobin is a major component of red blood cells, it is also present in neurons and glia. To examine whether the hemoglobin-derived peptides in brain are similar to those present in blood and heart, we used a peptidomics approach involving mass spectrometry. Many hemoglobin-derived peptides are found only in brain and not in blood, whereas all hemoglobin-derived peptides found in heart were also seen in blood. Thus, it is likely that the majority of the hemoglobin-derived peptides detected in brain are produced from brain hemoglobin and not erythrocytes. We also examined if the hemopressins and other major hemoglobin-derived peptides were regulated in the Cpefat/fat mouse; previously these mice were reported to have elevated levels of several hemoglobin-derived peptides. Many, but not all of the hemoglobin-derived peptides were elevated in several brain regions of the Cpefat/fat mouse. Taken together, these findings suggest that the post-translational processing of alpha and beta hemoglobin into the hemopressins, as well as other peptides, is upregulated in some but not all Cpefat/fat mouse brain regions. PMID:20202081

  4. Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats.

    Science.gov (United States)

    Ding, Shibin; Jiang, Jinjin; Zhang, Guofu; Bu, Yongjun; Zhang, Guanghui; Zhao, Xiangmei

    2017-01-01

    Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy. Eight-week-old male Wistar rats (40) were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw); and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER) stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw) and caloric restriction (30%) partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight. We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30%) and resveratrol (a pharmacological SIRT1 activator) supplementation

  5. Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats.

    Directory of Open Access Journals (Sweden)

    Shibin Ding

    Full Text Available Studies have demonstrated that resveratrol (a natural polyphenol and caloric restriction activate Sirtuin-1 (SIRT1 and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy.Eight-week-old male Wistar rats (40 were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw; and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw and caloric restriction (30% partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight.We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30% and resveratrol (a pharmacological SIRT1 activator

  6. Possible role of mechanical force in regulating regeneration of the vascularized fat flap inside a tissue engineering chamber.

    Science.gov (United States)

    Ye, Yuan; Yuan, Yi; Lu, Feng; Gao, Jianhua

    2015-12-01

    In plastic and reconstructive surgery, adipose tissue is widely used as effective filler for tissue defects. Strategies for treating soft tissue deficiency, which include free adipose tissue grafts, use of hyaluronic acid, collagen injections, and implantation of synthetic materials, have several clinical limitations. With the aim of overcoming these limitations, researchers have recently utilized tissue engineering chambers to produce large volumes of engineered vascularized fat tissue. However, the process of growing fat tissue in a chamber is still relatively limited, and can result in unpredictable or dissatisfactory final tissue volumes. Therefore, detailed understanding of the process is both necessary and urgent. Many studies have shown that mechanical force can change the function of cells via mechanotransduction. Here, we hypothesized that, besides the inflammatory response, one of the key factors to control the regeneration of vascularized fat flap inside a tissue engineering chamber might be the balance of mechanical forces. To test our hypothesis, we intend to change the balance of forces by means of measures in order to make the equilibrium point in favor of the direction of regeneration. If those measures proved to be feasible, they could be applied in clinical practice to engineer vascularized adipose tissue of predictable size and shape, which would in turn help in the advancement of tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. AMP-regulated protein kinase activity in the hearts of mice treated with low- or high-fat diet measured using novel LC-MS method.

    Science.gov (United States)

    Rybakowska, I M; Slominska, E M; Romaszko, P; Olkowicz, M; Kaletha, K; Smolenski, R T

    2015-06-01

    AMP-regulated protein kinase (AMPK) is involved in regulation of energy-generating pathways in response to the metabolic needs in different organs including the heart. The activity of AMPK is mainly controlled by AMP concentration that in turn could be affected by nucleotide metabolic pathways. This study aimed to develop a procedure for measurement of AMPK activity together with nucleotide metabolic enzymes and its application for studies of mice treated with high-fat diet. The method developed was based on analysis of conversion of AMARA peptide to pAMARA by partially purified heart homogenate by liquid chromatography/mass spectrometry (LC/MS). Activities of the enzymes of nucleotide metabolism were evaluated by analysis of conversion of substrates into products by HPLC. The method was applied for analysis of hearts of mice fed 12 weeks with low- (LFD) or high-fat diet (HFD). The optimized method for AMPK activity analysis (measured in presence of AMP) revealed change of activity from 0.089 ± 0.035 pmol/min/mg protein in LFD to 0.024 ± 0.002 in HFD. This coincided with increase of adenosine deaminase (ADA) activity from 0.11 ± 0.02 to 0.19 ± 0.06 nmol/mg tissue/min and decrease of AMP-deaminase (AMPD) activity from 1.26 ± 0.35 to 0.56 ± 0.15 nmol/mg tissue/min for LFD and HFD, respectively. We have proven quality of our LC/MS method for analysis of AMPK activity. We observed decrease in AMPK activity in the heart of mice treated with high-fat diet. However, physiological consequences of this change could be modulated by decrease in AMPD activity.

  8. Multiple Roles for UV RESISTANCE LOCUS8 in Regulating Gene Expression and Metabolite Accumulation in Arabidopsis under Solar Ultraviolet Radiation1[W][OA

    Science.gov (United States)

    Morales, Luis O.; Brosché, Mikael; Vainonen, Julia; Jenkins, Gareth I.; Wargent, Jason J.; Sipari, Nina; Strid, Åke; Lindfors, Anders V.; Tegelberg, Riitta; Aphalo, Pedro J.

    2013-01-01

    Photomorphogenic responses triggered by low fluence rates of ultraviolet B radiation (UV-B; 280–315 nm) are mediated by the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8). Beyond our understanding of the molecular mechanisms of UV-B perception by UVR8, there is still limited information on how the UVR8 pathway functions under natural sunlight. Here, wild-type Arabidopsis (Arabidopsis thaliana) and the uvr8-2 mutant were used in an experiment outdoors where UV-A (315–400 nm) and UV-B irradiances were attenuated using plastic films. Gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation, and leaf metabolite signatures were analyzed. The results show that UVR8 is required for transcript accumulation of genes involved in UV protection, oxidative stress, hormone signal transduction, and defense against herbivores under solar UV. Under natural UV-A irradiance, UVR8 is likely to interact with UV-A/blue light signaling pathways to moderate UV-B-driven transcript and PDX1 accumulation. UVR8 both positively and negatively affects UV-A-regulated gene expression and metabolite accumulation but is required for the UV-B induction of phenolics. Moreover, UVR8-dependent UV-B acclimation during the early stages of plant development may enhance normal growth under long-term exposure to solar UV. PMID:23250626

  9. Resistance to pathogens in terpene down-regulated orange fruits inversely correlates with the accumulation of D-limonene in peel oil glands.

    Science.gov (United States)

    Rodríguez, Ana; Shimada, Takehiko; Cervera, Magdalena; Redondo, Ana; Alquézar, Berta; Rodrigo, María Jesús; Zacarías, Lorenzo; Palou, Lluís; López, María M; Peña, Leandro

    2015-01-01

    Volatile organic compounds (VOCs) are secondary metabolites acting as a language for the communication of plants with the environment. In orange fruits, the monoterpene D-limonene accumulates at very high levels in oil glands from the peel. Drastic down-regulation of D-limonene synthase gene expression in the peel of transgenic oranges harboring a D-limonene synthase transgene in antisense (AS) configuration altered the monoterpene profile in oil glands, mainly resulting in reduced accumulation of D-limonene. This led to fruit resistance against Penicillium digitatum (Pd), Xanthomonas citri subsp. citri (Xcc) and other specialized pathogens. Here, we analyze resistance to pathogens in independent AS and empty vector (EV) lines, which have low, medium or high D-limonene concentrations and show that the level of resistance is inversely related to the accumulation of D-limonene in orange peels, thus explaining the need of high D-limonene accumulation in mature oranges in nature for the efficient attraction of specialized microorganism frugivores.

  10. Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

    Science.gov (United States)

    Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

    2016-03-29

    γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.

  11. Activating transcription factor 6 mediates oxidized LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating CHOP expression.

    Science.gov (United States)

    Yao, Shutong; Zong, Chuanlong; Zhang, Ying; Sang, Hui; Yang, Mingfeng; Jiao, Peng; Fang, Yongqi; Yang, Nana; Song, Guohua; Qin, Shucun

    2013-01-01

    This study was to explore whether activating transcription factor 6 (ATF6), an important sensor to endoplasmic reticulum (ER) stress, would mediate oxidized low-density lipoprotein (ox-LDL)- induced cholesterol accumulation and apoptosis in cultured macrophages and the underlying molecular mechanisms. Intracellular lipid droplets and total cholesterol levels were assayed by oil red O staining and enzymatic colorimetry, respectively. Cell viability and apoptosis were determined using MTT assay and AnnexinV-FITC apoptosis detection kit, respectively. The nuclear translocation of ATF6 in cells was detected by immunofluorescence analysis. Protein and mRNA levels were examined by Western blot analysis and real time-PCR, respectively. ATF6 siRNA was transfected to RAW264.7 cells by lipofectamin. Exposure of cells to ox-LDL induced glucose-regulated protein 78 (GRP78). C/EBP homologous protein (CHOP), a key-signaling component of ER stress-induced apoptosis, was up-regulated in ox-LDL-treated cells. ATF6, a factor that positively regulates CHOP expression, was activated by ox-LDL in a concentration- and time- dependent manner. The role of the ATF6-mediated ER stress pathway was further confirmed through the siRNA-mediated knockdown of ATF6, which attenuated ox-LDL-induced upregulation of CHOP, cholesterol accumulation and apoptosis in macrophages. In addition, the phosphorylation of double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK), another factor that positively regulates CHOP expression, was induced in the presence of ox-LDL, and PERK-specific siRNA also inhibited the ox-LDL-induced upregulation of CHOP and apoptosis in RAW264.7 cells. These results demonstrate that ER stress-related proteins, particularly ATF6 and its downstream molecule CHOP, are involved in ox-LDL-induced cholesterol accumulation and apoptosis in macrophages.

  12. Two LcbHLH transcription factors interacting with LcMYB1 in regulating late structural genes of anthocyanin biosynthesis in Nicotiana and Litchi chinensis during anthocyanin accumulation

    Directory of Open Access Journals (Sweden)

    Biao eLai

    2016-02-01

    Full Text Available Anthocyanin biosynthesis requires the MYB-bHLH-WD40 protein complex to activate the late biosynthetic genes. LcMYB1 was thought to act as key regulator in anthocyanin biosynthesis of litchi. However, basic helix-loop-helix proteins (bHLHs as partners have not been identified yet. The present study describes the functional characterization of three litchi bHLH candidate anthocyanin regulators, LcbHLH1, LcbHLH2 and LcbHLH3. Although these three litchi bHLHs phylogenetically clustered with bHLH proteins involved in anthcoyanin biosynthesis in other plant, only LcbHLH1 and LcbHLH3 were found to localize in the nucleus and physically interact with LcMYB1. The transcription levels of all these bHLHs were not coordinated with anthocyanin accumulation in different tissues and during development. However, when co-infiltrated with LcMYB1, both LcbHLH1 and LcbHLH3 enhanced anthocyanin accumulation in tobacco leaves with LcbHLH3 being the best inducer. Significant accumulation of anthocyanins in leaves transformed with the combination of LcMYB1 and LcbHLH3 were noticed, And this was associated with the up-regulation of two tobacco endogenous bHLH regulators, NtAn1a and NtAn1b, and late structural genes, like NtDFR and NtANS. Significant activity of the ANS promoter was observed in transient expression assays either with LcMYB1-LcbHLH1 or LcMYB1-LcbHLH3, while only minute activity was detected after transformation with only LcMYB1. In contrast, no activity was measured after induction with the combination of LcbHLH2 and LcMYB1. Higher DFR expression was also oberseved in paralleling with higher anthocyanins in co-transformed lines. LcbHLH1 and LcbHLH3 are essential partner of LcMYB1 in regulating the anthocyanin production in tobacco and probably also in litchi. The LcMYB1-LcbHLH complex enhanced anthocyanin accumulation may associate with activating the transcription of DFR and ANS.

  13. Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet.

    Science.gov (United States)

    Pehleman, Tanya L; Peters, Sandra J; Heigenhauser, George J F; Spriet, Lawrence L

    2005-01-01

    Whole body glucose disposal and skeletal muscle hexokinase, glycogen synthase (GS), pyruvate dehydrogenase (PDH), and PDH kinase (PDK) activities were measured in aerobically trained men after a standardized control diet (Con; 51% carbohydrate, 29% fat, and 20% protein of total energy intake) and a 56-h eucaloric, high-fat, low-carbohydrate diet (HF/LC; 5% carbohydrate, 73% fat, and 22% protein). An oral glucose tolerance test (OGTT; 1 g/kg) was administered after the Con and HF/LC diets with vastus lateralis muscle biopsies sampled pre-OGTT and 75 min after ingestion of the oral glucose load. The 90-min area under the blood glucose and plasma insulin concentration vs. time curves increased by 2-fold and 1.25-fold, respectively, after the HF/LC diet. The pre-OGTT fraction of GS in its active form and the maximal activity of hexokinase were not affected by the HF/LC diet. However, the HF/LC diet increased PDK activity (0.19 +/- 0.05 vs. 0.08 +/- 0.02 min(-1)) and decreased PDH activation (0.38 +/- 0.08 vs. 0.79 +/- 0.10 mmol acetyl-CoA.kg wet muscle(-1).min(-1)) before the OGTT vs. Con. During the OGTT, GS and PDH activation increased by the same magnitude in both diets, such that PDH activation remained lower during the HF/LC OGTT (0.60 +/- 0.11 vs. 1.04 +/- 0.09 mmol acetyl-CoA.kg(-1).min(-1)). These data demonstrate that the decreased glucose disposal during the OGTT after the 56-h HF/LC diet was in part related to decreased oxidative carbohydrate disposal in skeletal muscle and not to decreased glycogen storage. The rapid increase in PDK activity during the HF/LC diet appeared to account for the reduced potential for oxidative carbohydrate disposal.

  14. Regulation of metabolism by dietary carbohydrates in two lines of rainbow trout divergently selected for muscle fat content.

    Science.gov (United States)

    Kamalam, Biju Sam; Medale, Françoise; Kaushik, Sadasivam; Polakof, Sergio; Skiba-Cassy, Sandrine; Panserat, Stephane

    2012-08-01

    Previous studies in two rainbow trout lines divergently selected for lean (L) or fat (F) muscle suggested that they differ in their ability to metabolise glucose. In this context, we investigated whether genetic selection for high muscle fat content led to a better capacity to metabolise dietary carbohydrates. Juvenile trout from the two lines were fed diets with or without gelatinised starch (17.1%) for 10 weeks, after which blood, liver, muscle and adipose tissues were sampled. Growth rate, feed efficiency and protein utilisation were lower in the F line than in the L line. In both lines, intake of carbohydrates was associated with a moderate post-prandial hyperglycaemia, a protein sparing effect, an enhancement of nutrient (TOR-S6) signalling cascade and a decrease of energy-sensing enzyme (AMPK). Gene expression of hepatic glycolytic enzymes was higher in the F line fed carbohydrates compared with the L line, but concurrently transcripts for the gluconeogenic enzymes was also higher in the F line, possibly impairing glucose homeostasis. However, the F line showed a higher gene expression of hepatic enzymes involved in lipogenesis and fatty acid bioconversion, in particular with an increased dietary carbohydrate intake. Enhanced lipogenic potential coupled with higher liver glycogen content in the F line suggests better glucose storage ability than the L line. Overall, the present study demonstrates the changes in hepatic intermediary metabolism resulting from genetic selection for high muscle fat content and dietary carbohydrate intake without, however, any interaction for an improved growth or glucose utilisation in the peripheral tissues.

  15. The role of leptin and other hormones related to bone metabolism and appetite regulation as determinants of gain in body fat and fat-free mass in 8-11-year-old children.

    Science.gov (United States)

    Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni; Damsgaard, Camilla T; Petersen, Rikke A; Sørensen, Louise B; Ong, Ken K; Astrup, Arne; Mølgaard, Christian; Michaelsen, Kim F

    2015-03-01

    Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. We examined whether baseline fasting levels of ghrelin, adiponectin, leptin, insulin, IGF-I, osteocalcin, and intact parathyroid hormone (iPTH) were associated with body composition cross sectionally and longitudinally in 633 8-11-year-olds. Data on hormones and body composition by dual-energy x-ray absorptiometry from the OPUS School Meal Study were used. We looked at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (3 and 6 months) in FMI or FFMI using models with hormones individually or combined. Cross-sectionally, baseline leptin was positively associated with FMI in girls (0.211 kg/m(2) pr. μg/mL; 97.5% confidence interval [CI],0.186-0.236; P < .001) and boys (0.231 kg/m(2) pr. μg/mL; 97.5% CI, 0.200-0.261; P < .001). IGF-I in both sexes and iPTH in boys were positively associated with FMI. An inverse association between adiponectin and FFMI in boys and a positive association between IGF-I and FFMI were found in girls. In longitudinal models, baseline leptin was inversely associated with subsequent changes in FMI (-0.018 kg/m(2) pr. μg/mL; 97.5% CI, -0.034 - -0.002; P = .028) and FFMI (-0.014 kg/m(2) pr. μg/mL; 97.5% CI, -0.024 - -0.003; P = .006) in girls. Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.

  16. Passive and active roles of fat-free mass in the control of energy intake and body composition regulation

    OpenAIRE

    Dulloo, Abdul G.; Jacquet, Jean; Miles-Chan, Jennifer L; Schutz, Yves

    2017-01-01

    While putative feedback signals arising from adipose tissue are commonly assumed to provide the molecular links between the body’s long-term energy requirements and energy intake, the available evidence suggests that the lean body or fat-free mass (FFM) also plays a role in the drive to eat. A distinction must, however, be made between a ‘passive’ role of FFM in driving energy intake, which is likely to be mediated by ‘energy-sensing’ mechanisms that translate FFM-induced energy requirem...

  17. Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment

    DEFF Research Database (Denmark)

    Murholm, Maria; Dixen, Karen; Qvortrup, Klaus

    2009-01-01

    BACKGROUND: Brown adipocytes are specialised in dissipating energy through adaptive thermogenesis, whereas white adipocytes are specialised in energy storage. These essentially opposite functions are possible for two reasons relating to mitochondria, namely expression of uncoupling protein 1 (UCP1...... and brown fat, brown adipose tissue fractions and in selected adipose tissues during cold exposure. We find a massive induction of the majority of such genes during brown adipocyte differentiation and recruitment, e.g. of the mitochondrial transcription factors A (Tfam) and B2 (Tfb2m), whereas only a subset...

  18. Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation

    International Nuclear Information System (INIS)

    Yu, Jung Hwan; Lee, Yoo Jeong; Kim, Hyo Jung; Choi, Hyeonjin; Choi, Yoonjeong; Seok, Jo Woon; Kim, Jae-woo

    2015-01-01

    Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans. - Highlights: • PPARγ promotes MGAT1 expression in human primary hepatocytes. • PPARγ directly regulates MGAT1 promoter activity. • Human MGAT1 promoter has at least two PPARγ-binding elements. • Inhibition of MGAT1 expression attenuates hepatic lipid accumulation in humans

  19. Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jung Hwan [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Lee, Yoo Jeong [Division of Metabolic Disease, Center for Biomedical Sciences, National Institutes of Health, Cheongwon-gun, Chungbuk 363-951 (Korea, Republic of); Kim, Hyo Jung; Choi, Hyeonjin [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Choi, Yoonjeong; Seok, Jo Woon [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Kim, Jae-woo, E-mail: japol13@yuhs.ac [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2015-05-08

    Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans. - Highlights: • PPARγ promotes MGAT1 expression in human primary hepatocytes. • PPARγ directly regulates MGAT1 promoter activity. • Human MGAT1 promoter has at least two PPARγ-binding elements. • Inhibition of MGAT1 expression attenuates hepatic lipid accumulation in humans.

  20. Low Temperature-Induced 30 (LTI30 positively regulates drought stress resistance in Arabidopsis: effect on abscisic acid sensitivity and hydrogen peroxide accumulation

    Directory of Open Access Journals (Sweden)

    Haitao eShi

    2015-10-01

    Full Text Available As a dehydrin belonging to group II late embryogenesis abundant protein (LEA family, Arabidopsis Low Temperature-Induced 30 (LTI30/XERO2 has been shown to be involved in plant freezing stress resistance. However, the other roles of AtLTI30 remain unknown. In this study, we found that the expression of AtLTI30 was largely induced by drought stress and abscisic acid (ABA treatments. Thereafter, AtLTI30 knockout mutants and overexpressing plants were isolated to investigate the possible involvement of AtLTI30 in ABA and drought stress responses. AtLTI30 knockout mutants were less sensitive to ABA-mediated seed germination, while AtLTI30 overexpressing plants were more sensitive to ABA compared with wild type (WT. Consistently, the AtLTI30 knockout mutants displayed decreased drought stress resistance, while the AtLTI30 overexpressing plants showed improved drought stress resistance compared with WT, as evidenced by a higher survival rate and lower leaf water loss than WT after drought stress. Moreover, manipulation of AtLTI30 expression positively regulated the activities of catalases (CATs and endogenous proline content, as a result, negatively regulated drought stress-triggered hydrogen peroxide (H2O2 accumulation. All these results indicate that AtLTI30 is a positive regulator of plant drought stress resistance, partially through the modulation of ABA sensitivity, H2O2 and proline accumulation.

  1. H2O2 and NADPH oxidases involve in regulation of 2-(2-phenylethyl)chromones accumulation during salt stress in Aquilaria sinensis calli.

    Science.gov (United States)

    Wang, Xiaohui; Dong, Xianjuan; Feng, Yingying; Liu, Xiao; Wang, Jinling; Zhang, Zhongxiu; Li, Jun; Zhao, Yunfang; Shi, Shepo; Tu, Pengfei

    2018-04-01

    2-(2-Phenylethyl)chromones are the main compounds responsible for the quality of agarwood, which is widely used in traditional medicines, incenses and perfumes. H 2 O 2 and NADPH oxidases (also known as respiratory burst oxidase homologs, Rbohs) mediate diverse physiological and biochemical processes in environmental stress responses. However, little is known about the function of H 2 O 2 and NADPH oxidases in 2-(2-phenylethyl)chromones accumulation. In this study, we found that salt stress induced a transient increase in content of H 2 O 2 and 2-(2-phenylethyl)chromones accumulation in Aquilaria sinensis calli. Exogenous H 2 O 2 remarkably decreased the production of 2-(2-phenylethyl)chromones, while dimethylthiourea (DMTU), a scavenger of H 2 O 2 , significantly increased 2-(2-phenylethyl)chromones accumulation in salt treated calli. Three new H 2 O 2 -generating genes, named AsRbohA-C, were isolated and characterized from A. sinensis. Salt stress also induced a transient increase in AsRbohA-C expression and NADPH oxidase activity. Furthermore, exogenous H 2 O 2 increased AsRbohA-C expression and NADPH oxidase activity, while DMTU inhibited AsRbohA-C expression and NADPH oxidase activity under salt stress. Moreover, diphenylene iodonium (DPI), the inhibitor of NADPH oxidases, reduced AsRbohA-C expression and NADPH oxidase activity, but significantly induced 2-(2-phenylethyl)chromones accumulation during salt stress. These results clearly demonstrated the central role of H 2 O 2 and NADPH oxidases in regulation of salt-induced 2-(2-phenylethyl)chromones accumulation in A. sinensis calli. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism.

    Science.gov (United States)

    Sugimoto, Ryusei; Watanabe, Hiroshi; Ikegami, Komei; Enoki, Yuki; Imafuku, Tadashi; Sakaguchi, Yoshiaki; Murata, Michiya; Nishida, Kento; Miyamura, Shigeyuki; Ishima, Yu; Tanaka, Motoko; Matsushita, Kazutaka; Komaba, Hirotaka; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2017-03-01

    Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes. These effects were prevented by administration of the calcimimetic cinacalcet, a PTH suppressor, suggesting that PTH may down-regulate ABCG2 expression. This was directly tested in intestinal Caco-2 cells where the expression of ABCG2 on the plasma membrane was down-regulated by PTH (1-34) while its mRNA level remained unchanged. Interestingly, an inactive PTH derivative (13-34) had no effect, suggesting that a posttranscriptional regulatory system acts through the PTH receptor to regulate ABCG2 plasma membrane expression. As found in an animal study, additional clinical investigations showed that treatment with cinacalcet resulted in significant reductions in serum urate levels together with decreases in PTH levels in patients with secondary hyperparathyroidism undergoing dialysis. Thus, PTH down-regulates ABCG2 expression on the plasma membrane to suppress intestinal and renal urate excretion, and the effects of PTH can be prevented by cinacalcet treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  3. Role of Nitric Oxide Synthase on Blood Pressure Regulation and Vascular Function in Pregnant Rats on a High-Fat Diet.

    Science.gov (United States)

    Palei, Ana C; Spradley, Frank T; Granger, Joey P

    2017-03-01

    While obesity is a leading risk factor for preeclampsia, the mechanisms whereby obese women are more susceptible to pregnancy-induced hypertension are unclear. As high-fat diet (HFD) is an important contributor to the development of obesity, we tested the hypothesis that pregnant rats on HFD have hypertension and endothelial dysfunction due to reduced nitric oxide synthase (NOS). Twelve-week-old Sprague-Dawley female rats were fed normal diet (ND, 13% fat kcal) or HFD (40% fat kcal) for 9 weeks. Timed-pregnant rats were then generated and the effect of HFD on mean arterial blood pressure (MAP) and vascular function was assessed on gestational day (GD) 19. MAP was not different between HFD and ND pregnant rats. Intriguingly, sensitivity to acetylcholine-induced endothelium-dependent vasorelaxation was enhanced in small mesenteric arteries of HFD dams compared to ND controls (logEC50 -7.9 ± 0.3 vs. -6.7 ± 0.3 M; P hydrochloride (100 mg/l, drinking water) from GD 14 to 19. It was found that NOS inhibition increased MAP equally in HFD and ND groups. Contrary to our initial hypothesis, HFD dams were normotensive and presented increased endothelial function and NO/NOS3 levels. This enhanced NOS-mediated vascular function does not appear to have a major impact on blood pressure regulation of HFD-fed pregnant rats. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  4. Accumulation patterns of proper point defects in thermo-regulating coatings based on ZnO for space vehicles under electron irradiation

    International Nuclear Information System (INIS)

    Mikhajlov, M.M.; Sharafutdinova, V.V.

    1998-01-01

    The expansion of the band of the induced absorption of zinc oxide powders and thermo-regulating coatings based on ZnO for space vehicles is carried out after the 30 keV electron irradiation. Singularities of the growth of the intensity of individual components as a function of the accelerated electron flow are studied. It is found that power and exponential dependences with one or two components are characteristic for different color centers and different thermo-regulating coatings. The kinetics of the accumulation of free electrons is characterized by the maximum value of the electron flows at which the generation of color centers on pre-radiation defects is realized by the radiolysis of the pigment lattice

  5. Co-ordinate regulation of sterol biosynthesis enzyme activity during accumulation of sterols in developing rape and tobacco seed.

    Science.gov (United States)

    Harker, Mark; Hellyer, Amanda; Clayton, John C; Duvoix, Annelyse; Lanot, Alexandra; Safford, Richard

    2003-02-01

    The activities of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, sterol methyl transferase 1 and sterol acyltransferase, key enzymes involved in phytosterol biosynthesis were shown to be co-ordinately regulated during oilseed rape ( Brassica napus L.) and tobacco ( Nicotiana tabacum L.) seed development. In both plants, enzyme activities were low during the initial stages of seed development, increasing towards mid-maturation where they remained stable for a time, before declining rapidly as the oilseeds reached maturity. During seed development, the level of total sterols increased 12-fold in tobacco and 9-fold in rape, primarily due to an increase in steryl ester production. In both seed tissues, stages of maximum enzyme activity coincided with periods of high rates of sterol production, indicating developmental regulation of the enzymes to be responsible for the increases in the sterol content observed during seed development. Consistent with previous studies the data presented suggest that sterol biosynthesis is regulated by two key steps, although there may be others. The first is the regulation of carbon flux into the isoprenoid pathway to cycloartenol. The second is the flux from cycloartenol to Delta(5)-end-product sterols. The implications of the results in terms of enhancing seed sterol levels by genetic modification are also discussed.

  6. Glycogen synthase kinase-3beta (GSK3beta) negatively regulates PTTG1/human securin protein stability, and GSK3beta inactivation correlates with securin accumulation in breast tumors.

    Science.gov (United States)

    Mora-Santos, Mar; Limón-Mortés, M Cristina; Giráldez, Servando; Herrero-Ruiz, Joaquín; Sáez, Carmen; Japón, Miguel Á; Tortolero, Maria; Romero, Francisco

    2011-08-26

    PTTG1, also known as securin, is an inactivating partner of separase, the major effector for chromosome segregation during mitosis. At the metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome, allowing activation of separase. In addition, securin is overexpressed in metastatic or genomically instable tumors, suggesting a relevant role for securin in tumor progression. Stability of securin is regulated by phosphorylation; some phosphorylated forms are degraded out of mitosis, by the action of the SKP1-CUL1-F-box protein (SCF) complex. The kinases targeting securin for proteolysis have not been identified, and mechanistic insight into the cause of securin accumulation in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3β (GSK3β) phosphorylates securin to promote its proteolysis via SCF(βTrCP) E3 ubiquitin ligase. Importantly, a strong correlation between securin accumulation and GSK3β inactivation was observed in breast cancer tissues, indicating that GSK3β inactivation may account for securin accumulation in breast cancers.

  7. Gene Identification and Substrate Regulation Provide Insights into Sulfur Accumulation during Bioleaching with the Psychrotolerant Acidophile Acidithiobacillus ferrivorans

    Science.gov (United States)

    Liljeqvist, Maria; Rzhepishevska, Olena I.

    2013-01-01

    The psychrotolerant acidophile Acidithiobacillus ferrivorans has been identified from cold environments and has been shown to use ferrous iron and inorganic sulfur compounds as its energy sources. A bioinformatic evaluation presented in this study suggested that Acidithiobacillus ferrivorans utilized a ferrous iron oxidation pathway similar to that of the related species Acidithiobacillus ferrooxidans. However, the inorganic sulfur oxidation pathway was less clear, since the Acidithiobacillus ferrivorans genome contained genes from both Acidithiobacillus ferrooxidans and Acidithiobacillus caldus encoding enzymes whose assigned functions are redundant. Transcriptional analysis revealed that the petA1 and petB1 genes (implicated in ferrous iron oxidation) were downregulated upon growth on the inorganic sulfur compound tetrathionate but were on average 10.5-fold upregulated in the presence of ferrous iron. In contrast, expression of cyoB1 (involved in inorganic sulfur compound oxidation) was decreased 6.6-fold upon growth on ferrous iron alone. Competition assays between ferrous iron and tetrathionate with Acidithiobacillus ferrivorans SS3 precultured on chalcopyrite mineral showed a preference for ferrous iron oxidation over tetrathionate oxidation. Also, pure and mixed cultures of psychrotolerant acidophiles were utilized for the bioleaching of metal sulfide minerals in stirred tank reactors at 5 and 25°C in order to investigate the fate of ferrous iron and inorganic sulfur compounds. Solid sulfur accumulated in bioleaching cultures growing on a chalcopyrite concentrate. Sulfur accumulation halted mineral solubilization, but sulfur was oxidized after metal release had ceased. The data indicated that ferrous iron was preferentially oxidized during growth on chalcopyrite, a finding with important implications for biomining in cold environments. PMID:23183980

  8. Soil geochemical factors regulate Cd accumulation by metal hyperaccumulating Noccaea caerulescens (J. Presl & C. Presl) F.K. Mey in field-contaminated soils.

    Science.gov (United States)

    Rosenfeld, Carla E; Chaney, Rufus L; Martínez, Carmen E

    2018-03-01

    Cadmium contamination in soil is a substantial global problem, and of significant concern due to high food-chain transfer. Cadmium hyperaccumulators are of particular interest because of their ability to tolerate and take up significant amounts of heavy metal pollution from soils. One particular plant, Noccaea caerulescens (formerly, Thlaspi caerulescens), has been extensively studied in terms of its capacity to accumulate heavy metals (specifically Zn and Cd), though these studies have primarily utilized hydroponic and metal-spiked model soil systems. We studied Cd and nutrient uptake by two N. caerulescens ecotypes, Prayon (Zn-only hyperaccumulator) and Ganges (Zn- and Cd-hyperaccumulator) in four long-term field-contaminated soils. Our data suggest that individual soil properties such as total soil Cd, Zn:Cd molar ratio, or soil pH do not accurately predict Cd uptake by hyperaccumulating plants. Additionally, total Cd uptake by the hyperaccumulating Ganges ecotype was substantially less than its physiological capacity, which is likely due to Cd-containing solid phases (primarily iron oxides) and pH that play an important role in regulating and limiting Cd solubility. Increased P accumulation in the Ganges leaves, and greater plant Fe accumulation from Cd-containing soils suggests that rhizosphere alterations via proton, and potentially organic acid, secretion may also play a role in nutrient and Cd acquisition by the plant roots. The current study highlights the role that soil geochemical factors play in influencing Cd uptake by hyperaccumulating plants. While these plants may have high physiological potential to accumulate metals from contaminated soils, individual soil geochemical factors and the plant-soil interactions in that soil will dictate the actual amount of phytoextractable metal. This underlines the need for site-specific understanding of metal-containing solid phases and geochemical properties of soils before undertaking phytoextraction efforts

  9. Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity.

    Science.gov (United States)

    Kim, Jongwan; Yun, Eun-Young; Quan, Fu-Shi; Park, Seung-Won; Goo, Tae-Won

    2017-01-01

    The α -glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS).

  10. Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Jongwan Kim

    2017-01-01

    Full Text Available The α-glucosidase inhibitor, 1-deoxynojirimycin (DNJ, is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2/signal transducers and activators of transcription 3 (STAT3 signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS.

  11. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.

    2016-01-01

    Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...... is similar to the overflow metabolism observed in many other microorganisms, e.g. ethanol production by Sacchromyces cerevisiae at nitrogen limitation....

  12. Permeabilization of enterocytes induced by absorption of dietary fat

    DEFF Research Database (Denmark)

    Danielsen, Erik Michael; Hansen, Gert H; Rasmussen, Karina

    2013-01-01

    the physiological process of dietary fat absorption, and short exposures to the fat mixture caused fat droplet accumulation within villus enterocytes. Lucifer yellow (LY), a fluorescent membrane-impermeable polar tracer was included to monitor epithelial integrity. Both in controls and during fat absorption LY...

  13. ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans.

    Science.gov (United States)

    Subramaniam, Selvakumar; Ozdener, Mehmet Hakan; Abdoul-Azize, Souleymane; Saito, Katsuyoshi; Malik, Bilal; Maquart, Guillaume; Hashimoto, Toshihiro; Marambaud, Philippe; Aribi, Mourad; Tordoff, Michael G; Besnard, Philippe; Khan, Naim Akhtar

    2016-10-01

    Obesity is a major public health problem. An in-depth knowledge of the molecular mechanisms of oro-sensory detection of dietary lipids may help fight it. Humans and rodents can detect fatty acids via lipido-receptors, such as CD36 and GPR120. We studied the implication of the MAPK pathways, in particular, ERK1/2, in the gustatory detection of fatty acids. Linoleic acid, a dietary fatty acid, induced via CD36 the phosphorylation of MEK1/2-ERK1/2-ETS-like transcription factor-1 cascade, which requires Fyn-Src kinase and lipid rafts in human taste bud cells (TBCs). ERK1/2 cascade was activated by Ca 2+ signaling via opening of the calcium-homeostasis modulator-1 (CALHM1) channel. Furthermore, fatty acid-evoked Ca 2+ signaling and ERK1/2 phosphorylation were decreased in both human TBCs after small interfering RNA knockdown of CALHM1 channel and in TBCs from Calhm1 -/- mice. Targeted knockdown of ERK1/2 by small interfering RNA or PD0325901 (MEK1/2 inhibitor) in the tongue and genetic ablation of Erk1 or Calhm1 genes impaired preference for dietary fat in mice. Lingual inhibition of ERK1/2 in healthy volunteers also decreased orogustatory sensitivity for linoleic acid. Our data demonstrate that ERK1/2-MAPK cascade is regulated by the opening of CALHM1 Ca 2+ channel in TBCs to modulate orogustatory detection of dietary lipids in mice and humans.-Subramaniam, S., Ozdener, M. H., Abdoul-Azize, S., Saito, K., Malik, B., Maquart, G., Hashimoto, T., Marambaud, P., Aribi, M., Tordoff, M. G., Besnard, P., Khan, N. A. ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans. © FASEB.

  14. Accumulative effects of regulatory actions. Exercise of analysis of CER, consideration of the cumulative Effects of regulation in the rulemaking process in Spanish NPP

    International Nuclear Information System (INIS)

    Gonzalez Ayestaran, P.; Castella, L.

    2014-01-01

    Through its interaction with the American industry, the NRC has been aware for a number of years of the concern about the impact of the accumulative effect of some regulatory actions. In response to this concern, which was highlighted by the industry, the NRC has carried out initiative to review a number of regulatory requirements order to ensure that NRC regulation and practices dno not lead to an unnecessary regulatory load. The foregoing was in response to what has become commonly known as the CER. Cumulative Effects of Regulation in the Rulemaking Process. In view of the regulatory actuation by the Spanish Nuclear Safety Council (CSN) and, in particular after the events which occurred in Japan, a pilot study has been carried out to examine the CER on a Spanish plant in order to analyse the cumulative effects of regulation and to propose improvements to the management of regulation in line with that set our by the NRC in various documents (SECY-02-081, SECY-11-0032 among others). (Authors)

  15. Seasoning ingredients in a medium-fat diet regulate lipid metabolism in peripheral tissues via the hypothalamic-pituitary axis in growing rats.

    Science.gov (United States)

    Tanaka, Mitsuru; Yasuoka, Akihito; Yoshinuma, Haruka; Saito, Yoshikazu; Asakura, Tomiko; Tanabe, Soichi

    2018-03-01

    We fed rats noodle (N) -diet containing 30 wt.% instant noodle with a 26% fat-to-energy ratio for 30 days (N-group). Compared with rats that were fed the same amount of nutrients (C-group), the N-group showed lower liver triacylglycerol levels and higher fecal cholesterol levels. We then analyzed transcriptome of the hypothalamic-pituitary (HP), the liver and the white adipose tissue (WAT). Thyroid stimulating hormone (Tshb), and its partner, glycoprotein hormone genes were up-regulated in the HP of N-group. Sterol regulatory element binding transcription factors were activated in the liver of N-group, while an up-regulation of the angiogenic signal occurred in the WAT of N-group. N-group showed higher urine noradrenaline (NA) level suggesting that these tissue signals are regulated by NA and Tshb. The N-diet contains 0.326 wt.% glutamate, 0.00236 wt.% 6-shogaol and Maillard reaction products. Our results suggest that these ingredients may affect lipid homeostasis via the HP axis.

  16. CCAAT/Enhancer-Binding Protein α Is a Crucial Regulator of Human Fat Mass and Obesity Associated Gene Transcription and Expression

    Directory of Open Access Journals (Sweden)

    Wei Ren

    2014-01-01

    Full Text Available Several susceptibility loci have been reported associated with obesity and T2DM in GWAS. Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes in diverse patient populations. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. While much is known about the epigenetic mutations contributing to obesity and T2DM, less is certain with the expression regulation of FTO gene. In this study, a highly conserved canonical C/EBPα binding site was located around position −45~−54 bp relative to the human FTO gene transcriptional start site. Site-directed mutagenesis of the putative C/EBPα binding sites decreased FTO promoter activity. Overexpression and RNAi studies also indicated that C/EBPα was required for the expression of FTO. Chromatin immunoprecipitation (ChIP experiment was carried out and the result shows direct binding of C/EBPα to the putative binding regions in the FTO promoter. Collectively, our data suggest that C/EBPα may act as a positive regulator binding to FTO promoter and consequently, activates the gene transcription.

  17. Identification of differentially accumulated proteins involved in regulating independent and combined osmosis and cadmium stress response in Brachypodium seedling roots.

    Science.gov (United States)

    Chen, Ziyan; Zhu, Dong; Wu, Jisu; Cheng, Zhiwei; Yan, Xing; Deng, Xiong; Yan, Yueming

    2018-05-17

    In this study, we aimed to identify differentially accumulated proteins (DAPs) involved in PEG mock osmotic stress, cadmium (Cd 2+ ) stress, and their combined stress responses in Brachypodium distachyon seedling roots. The results showed that combined PEG and Cd 2+ stresses had more significant effects on Brachypodium seedling root growth, physiological traits, and ultrastructures when compared with each individual stress. Totally, 106 DAPs were identified that are responsive to individual and combined stresses in roots. These DAPs were mainly involved in energy metabolism, detoxification and stress defense and protein metabolism. Principal component analysis revealed that DAPs from Cd 2+ and combined stress treatments were grouped closer than those from osmotic stress treatment, indicating that Cd 2+ and combined stresses had more severe influences on the root proteome than osmotic stress alone. Protein-protein interaction analyses highlighted a 14-3-3 centered sub-network that synergistically responded to osmotic and Cd 2+ stresses and their combined stresses. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 14 key DAP genes revealed that most genes showed consistency between transcriptional and translational expression patterns. A putative pathway of proteome metabolic changes in Brachypodium seedling roots under different stresses was proposed, which revealed a complicated synergetic responsive network of plant roots to adverse environments.

  18. Organic carbon mass accumulation rate regulates the flux of reduced substances from the sediments of deep lakes

    Directory of Open Access Journals (Sweden)

    T. Steinsberger

    2017-07-01

    Full Text Available The flux of reduced substances, such as methane and ammonium, from the sediment to the bottom water (Fred is one of the major factors contributing to the consumption of oxygen in the hypolimnia of lakes and thus crucial for lake oxygen management. This study presents fluxes based on sediment porewater measurements from different water depths of five deep lakes of differing trophic states. In meso- to eutrophic lakes Fred was directly proportional to the total organic carbon mass accumulation rate (TOC-MAR of the sediments. TOC-MAR and thus Fred in eutrophic lakes decreased systematically with increasing mean hypolimnion depth (zH, suggesting that high oxygen concentrations in the deep waters of lakes were essential for the extent of organic matter mineralization leaving a smaller fraction for anaerobic degradation and thus formation of reduced compounds. Consequently, Fred was low in the 310 m deep meso-eutrophic Lake Geneva, with high O2 concentrations in the hypolimnion. By contrast, seasonal anoxic conditions enhanced Fred in the deep basin of oligotrophic Lake Aegeri. As TOC-MAR and zH are based on more readily available data, these relationships allow estimating the areal O2 consumption rate by reduced compounds from the sediments where no direct flux measurements are available.

  19. Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells.

    Directory of Open Access Journals (Sweden)

    Mehmet Yabas

    Full Text Available Natural killer T (NKT cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo and mature (NK1.1(hi cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder, that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.

  20. Regulation of hepatic branched-chain alpha-keto acid dehydrogenase complex in rats fed a high-fat diet

    Science.gov (United States)

    Objective: Branched-chain alpha-keto acid dehydrogenase complex (BCKDC) regulates branched-chain amino acid (BCAA) metabolism at the level of branched chain alpha-ketoacid (BCKA) catabolism. It has been demonstrated that the activity of hepatic BCKDC is markedly decreased in type 2 diabetic animal...

  1. Fat heaps

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; Katajainen, Jyrki

    This report is an electronic appendix to our paper \\Fat heaps without regular counters". In that paper we described a new variant of fat heaps that is conceptually simpler and easier to implement than the original version. We also compared the practical performance of this data structure...

  2. Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology.

    Science.gov (United States)

    Bergen, Werner G; Brandebourg, Terry D

    2016-06-01

    For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review. © 2016 by the Society for Experimental Biology and Medicine.

  3. The Jasmonate-ZIM-domain proteins interact with the WD-Repeat/bHLH/MYB complexes to regulate Jasmonate-mediated anthocyanin accumulation and trichome initiation in Arabidopsis thaliana.

    Science.gov (United States)

    Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

    2011-05-01

    Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)-based SCF(COI1) complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation.

  4. The Jasmonate-ZIM-Domain Proteins Interact with the WD-Repeat/bHLH/MYB Complexes to Regulate Jasmonate-Mediated Anthocyanin Accumulation and Trichome Initiation in Arabidopsis thaliana[C][W

    Science.gov (United States)

    Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

    2011-01-01

    Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)–based SCFCOI1 complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation. PMID:21551388

  5. Effect of increasing body condition on key regulators of fat metabolism in subcutaneous adipose tissue depot and circulation of nonlactating dairy cows.

    Science.gov (United States)

    Locher, L; Häussler, S; Laubenthal, L; Singh, S P; Winkler, J; Kinoshita, A; Kenéz, Á; Rehage, J; Huber, K; Sauerwein, H; Dänicke, S

    2015-02-01

    In response to negative energy balance, overconditioned cows mobilize more body fat than thin cows and subsequently are prone to develop metabolic disorders. Changes in adipose tissue (AT) metabolism are barely investigated in overconditioned cows. Therefore, the objective was to investigate the effect of increasing body condition on key regulator proteins of fat metabolism in subcutaneous AT and circulation of dairy cows. Nonlactating, nonpregnant dairy cows (n=8) investigated in the current study served as a model to elucidate the changes in the course of overcondition independent from physiological changes related to gestation, parturition, and lactation. Cows were fed diets with increasing portions of concentrate during the first 6wk of the experiment until 60% were reached, which was maintained for 9wk. Biopsy samples from AT of the subcutaneous tailhead region were collected every 8wk, whereas blood was sampled monthly. Within the experimental period cows had an average BW gain of 243±33.3 kg. Leptin and insulin concentrations were increased until wk 12. Based on serum concentrations of glucose, insulin, and nonesterified fatty acids, the surrogate indices for insulin sensitivity were calculated. High-concentrate feeding led to decreased quantitative insulin sensitivity check index and homeostasis model assessment due to high insulin and glucose concentrations indicating decreased insulin sensitivity. Adiponectin, an adipokine-promoting insulin sensitivity, decreased in subcutaneous AT, but remained unchanged in the circulation. The high-concentrate diet affected key enzymes reflecting AT metabolism such as AMP-activated protein kinase and hormone-sensitive lipase, both represented as the proportion of the phosphorylated protein to total protein, as well as fatty acid synthase. The extent of phosphorylation of AMP-activated protein kinase and the protein expression of fatty acid synthase were inversely regulated throughout the experimental period, whereas

  6. Down-regulation of vascular PPAR-γ contributes to endothelial dysfunction in high-fat diet-induced obese mice exposed to chronic intermittent hypoxia.

    Science.gov (United States)

    Zhang, Yanan; Zhang, Chunlian; Li, Haiou; Hou, Jingdong

    2017-10-14

    Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is associated with endothelial dysfunction. The prevalence of OSA is linked to an epidemic of obesity. CIH has recently been reported to cause endothelial dysfunction in diet-induced obese animals by exaggerating oxidative stress and inflammation, but the underlying mechanism remains unclear. PPAR-γ, a ligand-inducible transcription factor that exerts anti-oxidant and anti-inflammatory effects, is down-regulated in the peripheral tissues in diet-induce obesity. We tested the hypothesis that down-regulation of vascular PPAR-γ in diet-induced obesity enhances inflammation and oxidative stress in response to CIH, resulting in endothelial dysfunction. Male C57BL/6 mice were fed either a high-fat diet (HFD) or a low-fat diet (LFD) and simultaneously exposed to CIH or intermittent air for 6 weeks. An additional HFD group received a combination of CIH and PPAR-γ agonist pioglitazone for 6 weeks. Endothelial-dependent vasodilation was impaired only in HFD group exposed to CIH, compared with other groups, but was restored by concomitant pioglitazone treatment. Molecular studies revealed that vascular PPAR-γ expression and activity were reduced in HFD groups, compared with LFD groups, but were reversed by pioglitazone treatment. In addition, CIH elevated vascular expression of NADPH oxidase 4 and dihydroethidium fluorescence, and increased expression of proinflammatory cytokines TNF-α and IL-1β in both LFD and HFD groups, but these increases was significantly greater in HFD group, along with decreased vascular eNOS activity. Pioglitazone treatment of HFD group prevented CIH-induced changes in above molecular markers. The results suggest that HFD-induced obesity down-regulates vascular PPAR-γ, which results in exaggerated oxidative stress and inflammation in response to CIH, contributing to endothelial dysfunction. This finding may provide new insights into the mechanisms by which OSA

  7. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation.

    Science.gov (United States)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie; Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique; Revers, Frédéric; Ziegler-Graff, Véronique; Brault, Véronique

    2015-12-01

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RTCter) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RTCter. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Regulation of photosynthesis by end-product accumulation in leaves of plants storing starch, sucrose, and hexose sugars.

    Science.gov (United States)

    Goldschmidt, E E; Huber, S C

    1992-08-01

    demonstrate the possibility of the occurrence of end-product inhibition of photosynthesis in a large number of crop plants. The long-term inhibition of photosynthesis in girdled leaves is not confined to stomatal responses since the A(max) declined up to 50%. The inhibition of A(max) by girdling was strongest in starch storers, but starch itself cannot be directly responsible, because the starchless mutant of N. sylvestris was also strongly inhibited. Similarly, the inhibition cannot be attributed to hexose sugars either, because soybean, cotton, and cucumber are among the plants most strongly inhibited although they do not maintain a large hexose pool. Spinach, a sucrose storer, showed the least inhibition in both girdled and excised leaf systems, which indicates that sucrose is probably not directly responsible for the end-product inhibition of photosynthesis. The occurrence of strong end-product inhibition appears to be correlated with high acid-invertase activity in fully expanded leaves. The inhibition may be related to the nature of soluble sugar metabolism in the extrachloroplastic compartment and may be caused by a metabolite that has different rates of accumulation and turnover in sucrose storers and other plants.

  9. Abundance of adiponectin system and G-protein coupled receptor GPR109A mRNA in adipose tissue and liver of F2 offspring cows of Charolais × German Holstein crosses that differ in body fat accumulation.

    Science.gov (United States)

    Mielenz, M; Kuhla, B; Hammon, H M

    2013-01-01

    In addition to its role in energy storage, adipose tissue (AT) is an important endocrine organ and it secretes adipokines. The adipokine adiponectin improves insulin sensitivity by activation of its receptors AdipoR1 and AdipoR2. Lipolysis in AT is downregulated by the G-protein coupled receptor (GPR109A), which binds the endogenous ligand β-hydroxybutyrate (BHBA). Insulin sensitivity is reduced during the transition from late pregnancy to early lactation in dairy cattle and BHBA is increased postpartum, implying the involvement of the adiponectin system and GPR109A in this process. The aim of the current investigation was to study the effect of the genetic background of cows on the mRNA abundance of the adiponectin system, as well as GPR109A, in an F(2) population of 2 Charolais × German Holstein families. These families were deduced from full- and half-sibs sharing identical but reciprocal paternal and maternal Charolais grandfathers. The animals of the 2 families showed significant differences in fat accretion and milk secretion and were designated fat-type (high fat accretion but low milk production) and lean-type (low fat accretion but high milk production). The mRNA of the adiponectin system and GPR109A were quantified by real-time PCR in different fat depots (subcutaneous from back, mesenteric, kidney) and liver. The mRNA data were correlated with AT masses (intermuscular topside border fat, kidney, mesenteric, omental, total inner fat mass, total subcutaneous fat mass, and total fat mass) and blood parameters (glucose, nonesterified fatty acids, BHBA, urea, insulin, and glucagon). The abundance of adiponectin system mRNA was higher in discrete AT depots of fat-type cows [adiponectin mRNA in mesenteric fat (trend), AdipoR1 in kidney and mesenteric AT, and AdipoR2 in subcutaneous fat (trend)] than in lean-type cows. More GPR109A mRNA was found in kidney fat of the lean-type family than in that of the fat-type family. In liver, the abundance of AdipoR2 and

  10. Wnt/β-Catenin Signaling Activation beyond Robust Nuclear β-Catenin Accumulation in Nondysplastic Barrett’s Esophagus: Regulation via Dickkopf-1

    Directory of Open Access Journals (Sweden)

    Orestis Lyros

    2015-07-01

    Full Text Available INTRODUCTION: Wnt/β-catenin signaling activation has been reported only during the late steps of Barrett’s esophagus (BE neoplastic progression, but not in BE metaplasia, based on the absence of nuclear β-catenin. However, β-catenin transcriptional activity has been recorded in absence of robust nuclear accumulation. Thus, we aimed to investigate the Wnt/β-catenin signaling in nondysplastic BE. METHODS: Esophageal tissues from healthy and BE patients without dysplasia were analyzed for Wnt target gene expression by quantitative reverse transcription polymerase chain reaction (qRT-PCR and immunohistochemistry. Esophageal squamous (EPC1-& EPC2-hTERT, BE metaplastic (CP-A, and adenocarcinoma (OE33 cell lines were characterized for Wnt activation by qRT-PCR, Western blot, and luciferase assay. Wnt activity regulation was examined by using recombinant Wnt3a and Dickkopf-1 (Dkk1 as well as Dkk1 short interfering RNA. RESULTS: Wnt target genes (AXIN2, c-MYC, Cyclin D1, Dkk1 and Wnt3a were significantly upregulated in nondysplastic BE compared with squamous mucosa. Elevated levels of dephosphorylated β-catenin were detected in nondysplastic BE. Nuclear active β-catenin and TOPflash activity were increased in CP-A and OE33 cells compared with squamous cells. Wnt3a-mediated β-catenin signaling activation was abolished by Dkk1 in CP-A cells. TOPFlash activity was elevated following Dkk1 silencing in CP-A but not in OE33 cells. Dysplastic and esophageal adenocarcinoma tissues demonstrated further Dkk1 and AXIN2 overexpression. CONCLUSIONS: Despite the absence of robust nuclear accumulation, β-catenin is transcriptionally active in nondysplastic BE. Dkk1 overexpression regulates β-catenin signaling in BE metaplastic but not in adenocarcinoma cells, suggesting that early perturbation of Dkk1-mediated signaling suppression may contribute to BE malignant transformation.

  11. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France); Chapuis, Sophie [Institut de Biologie Moléculaire des Plantes, Laboratoire propre du CNRS conventionné avec l’Université de Strasbourg, 12 rue du Général Zimmer, 67084 Strasbourg (France); Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France); Revers, Frédéric [INRA, Université de Bordeaux, UMR 1332 de Biologie du Fruit et Pathologie, 33882 Villenave d’Ornon (France); Ziegler-Graff, Véronique [Institut de Biologie Moléculaire des Plantes, Laboratoire propre du CNRS conventionné avec l’Université de Strasbourg, 12 rue du Général Zimmer, 67084 Strasbourg (France); Brault, Véronique, E-mail: veronique.brault@colmar.inra.fr [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France)

    2015-12-15

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74 kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RT{sub Cter}) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RT{sub Cter}. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. - Highlights: • The C-terminal domain of TuYV-RT is required for long-distance movement. • CIPK7 from Arabidopsis interacts with RT{sub Cter} in yeast and in plants. • CIPK7 overexpression increases virus titer locally but not virus systemic movement. • CIPK7 localizes to plasmodesmata. • CIPK7 could be a defense protein regulating virus export.

  12. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation

    International Nuclear Information System (INIS)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie; Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique; Revers, Frédéric; Ziegler-Graff, Véronique; Brault, Véronique

    2015-01-01

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74 kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RT_C_t_e_r) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RT_C_t_e_r. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. - Highlights: • The C-terminal domain of TuYV-RT is required for long-distance movement. • CIPK7 from Arabidopsis interacts with RT_C_t_e_r in yeast and in plants. • CIPK7 overexpression increases virus titer locally but not virus systemic movement. • CIPK7 localizes to plasmodesmata. • CIPK7 could be a defense protein regulating virus export.

  13. Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase expression by Zingiber officinale in the liver of high-fat diet-fed rats.

    Science.gov (United States)

    Nammi, Srinivas; Kim, Moon S; Gavande, Navnath S; Li, George Q; Roufogalis, Basil D

    2010-05-01

    Zingiber officinale has been used to control lipid disorders and reported to possess remarkable cholesterol-lowering activity in experimental hyperlipidaemia. In the present study, the effect of a characterized and standardized extract of Zingiber officinale on the hepatic lipid levels as well as on the hepatic mRNA and protein expression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated in a high-fat diet-fed rat model. Rats were treated with an ethanol extract of Zingiber officinale (400 mg/kg) extract along with a high-fat diet for 6 weeks. The extract of Zingiber officinale significantly decreased hepatic triglyceride and tended to decrease hepatic cholesterol levels when administered over 6 weeks to the rats fed a high-fat diet. We found that in parallel, the extract up-regulated both LDL receptor mRNA and protein level and down-regulated HMG-CoA reductase protein expression in the liver of these rats. The metabolic control of body lipid homeostasis is in part due to enhanced cholesterol biosynthesis and reduced expression of LDL receptor sites following long-term consumption of high-fat diets. The present results show restoration of transcriptional and post-transcriptional changes in low-density lipoprotein and HMG CoA reductase by Zingiber officinale administration with a high-fat diet and provide a rational explanation for the effect of ginger in the treatment of hyperlipidaemia.

  14. Alleviation of reactive oxygen species enhances PUFA accumulation in Schizochytrium sp. through regulating genes involved in lipid metabolism

    Directory of Open Access Journals (Sweden)

    Sai Zhang

    2018-06-01

    Full Text Available The unicellular heterotrophic thraustochytrids are attractive candidates for commercial polyunsaturated fatty acids (PUFA production. However, the reactive oxygen species (ROS generated in their aerobic fermentation process often limits their PUFA titer. Yet, the specific mechanisms of ROS involvement in the crosstalk between oxidative stress and intracellular lipid synthesis remain poorly described. Metabolic engineering to improve the PUFA yield in thraustochytrids without compromising growth is an important aspect of economic feasibility. To fill this gap, we overexpressed the antioxidative gene superoxide dismutase (SOD1 by integrating it into the genome of thraustochytrid Schizochytrium sp. PKU#Mn4 using a novel genetic transformation system. This study reports the ROS alleviation, enhanced PUFA production and transcriptome changes resulting from the SOD1 overexpression. SOD1 activity in the recombinant improved by 5.2–71.6% along with 7.8–38.5% decline in ROS during the fermentation process. Interestingly, the total antioxidant capacity in the recombinant remained higher than wild-type and above zero in the entire process. Although lipid profile was similar to that of wild-type, the concentrations of major fatty acids in the recombinant were significantly (p ≤ 0.05 higher. The PUFA titer increased up to 1232 ± 41 mg/L, which was 32.9% higher (p ≤ 0.001 than the wild type. Transcriptome analysis revealed strong downregulation of genes potentially involved in β-oxidation of fatty acids in peroxisome and upregulation of genes catalyzing lipid biosynthesis. Our results enrich the knowledge on stress-induced PUFA biosynthesis and the putative role of ROS in the regulation of lipid metabolism in oleaginous thraustochytrids. This study provides a new and alternate strategy for cost-effective industrial fermentation of PUFA. Keywords: Polyunsaturated fatty acids, Schizochytrium sp., Superoxide dismutase, Transgene

  15. Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up‐regulation contribute to the onset of diabetic cardiomyopathy

    Science.gov (United States)

    Ma, Heng; Li, Shi‐Yan; Xu, Peisheng; Babcock, Sara A.; Dolence, E. Kurt; Brownlee, Michael; Li, Ji

    2008-01-01

    Abstract Diabetic cardiomyopathy is manifested by compromised systolic and diastolic function. This study was designed to examine the role of advanced glycation endproduct (AGE) and AGE receptor (RAGE) in diabetic cardiomyopathy. Heart function was assessed in isolated control and streptozotocin‐induced diabetic hearts following in vivo RAGE gene knockdown using RNA interference. Cardiomyocyte mechanical properties were evaluated including peak shortening (PS), time‐to‐PS (TPS) and time‐to‐90% relengthening (TR90). RAGE was assayed by RT‐PCR and immunoblot. Diabetes significantly enhanced cardiac MG, AGE and RAGE levels accompanied with colocalization of AGE and RAGE in cardiomyocytes. Diabetes‐elicited increase in RAGE was inhibited by in vivo siRNA interference. The AGE formation inhibitor benfotiamine significantly attenuated diabetes‐induced elevation in MG, AGE, RAGE and collagen cross‐linking without affecting hypertriglyceridaemia and hypercholesterolaemia in diabetes. Diabetes markedly decreased LV contractility, as evidenced by reduced ±dP/dt and LV developed pressure (LVDP), which were protected by RAGE gene knockdown. In addition, MG‐derived AGE (MG‐AGE) up‐regulated cardiac RAGE mRNA and triggered cardiomyocyte contractile dysfunction reminiscent of diabetic cardiomyopathy. The MG‐AGE‐elicited prolongation of TPS and TR90 was ablated by an anti‐RAGE antibody in cardiomyocytes. Interestingly, MG‐AGE‐induced cardiomyocyte dysfunction was associated with mitochondrial membrane potential (MMP) depolarization and reduced GSK‐3β inactivation in control cardiomyocytes, similar to those from in vivo diabetes. Treatment with siRNA‐RAGE ablated diabetes‐induced MMP depolarization and GSK‐3β inactivation. Collectively, our result implicated a role of AGE‐RAGE in the pathogenesis of diabetic cardiomyopathy. PMID:19602045

  16. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

    Science.gov (United States)

    Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-04-01

    The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Increased expression of PPARγ in high fat diet-induced liver steatosis in mice

    International Nuclear Information System (INIS)

    Inoue, Mitsutaka; Ohtake, Takaaki; Motomura, Wataru; Takahashi, Nobuhiko; Hosoki, Yayoi; Miyoshi, Shigeki; Suzuki, Yasuaki; Saito, Hiroyuki; Kohgo, Yutaka; Okumura, Toshikatsu

    2005-01-01

    The present study was performed to examine a hypothesis that peroxisome proliferator-activated receptor γ (PPARγ) is implicated in high fat diet-induced liver steatosis. Mice were fed with control or high fat diet containing approximately 10% or 80% cholesterol, respectively. Macroscopic and microscopic findings demonstrated that lipid accumulation in the liver was observed as early as 2 weeks after high fat diet and that high fat diet for 12 weeks developed a fatty liver phenotype, establishing a novel model of diet-induced liver steatosis. Gene profiling with microarray and real-time PCR studies demonstrated that among genes involved in lipid metabolism, adipogenesis-related genes, PPARγ and its targeted gene, CD36 mRNA expression was specifically up-regulated in the liver by high fat diet for 2 weeks. Immunohistochemical study revealed that PPARγ protein expression is increased in the nuclei of hepatocytes by high fat diet. It was also shown that protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPARγ, in the liver was drastically suppressed by high fat diet. All these results suggest for the first time that the CREB-PPARγ signaling pathway may be involved in the high fat diet-induced liver steatosis

  18. MdATG18a overexpression improves tolerance to nitrogen deficiency and regulates anthocyanin accumulation through increased autophagy in transgenic apple.

    Science.gov (United States)

    Sun, Xun; Jia, Xin; Huo, Liuqing; Che, Runmin; Gong, Xiaoqing; Wang, Ping; Ma, Fengwang

    2018-02-01

    Nitrogen (N) availability is an essential factor for plant growth. Recycling and remobilization of N have strong impacts on crop yield and quality under N deficiency. Autophagy is a critical nutrient-recycling process that facilitates remobilization under starvation. We previously showed that an important AuTophaGy (ATG) protein from apple, MdATG18a, has a positive role in drought tolerance. In this study, we explored its biological role in response to low-N. Overexpression of MdATG18a in both Arabidopsis and apple improved tolerance to N-depletion and caused a greater accumulation of anthocyanin. The increased anthocyanin concentration in transgenic apple was possibly due to up-regulating flavonoid biosynthetic and regulatory genes (MdCHI, MdCHS, MdANS, MdPAL, MdUFGT, and MdMYB1) and higher soluble sugars concentration. MdATG18a overexpression enhanced starch degradation with up-regulating amylase gene (MdAM1) and up-regulated sugar metabolism related genes (MdSS1, MdHXKs, MdFK1, and MdNINVs). Furthermore, MdATG18a functioned in nitrate uptake and assimilation by up-regulating nitrate reductase MdNIA2 and 3 high-affinity nitrate transporters MdNRT2.1/2.4/2.5. MdATG18a overexpression also elevated other important MdATG genes expression and autophagosomes formation under N-depletion, which play key contributions to above changes. Together, these results demonstrate that overexpression of MdATG18a enhances tolerance to N-deficiencies and plays positive roles in anthocyanin biosynthesis through greater autophagic activity. © 2017 John Wiley & Sons Ltd.

  19. Campylobacter jejuni CsrA complements an Escherichia coli csrA mutation for the regulation of biofilm formation, motility and cellular morphology but not glycogen accumulation

    Science.gov (United States)

    2012-01-01

    Background Although Campylobacter jejuni is consistently ranked as one of the leading causes of bacterial diarrhea worldwide, the mechanisms by which C. jejuni causes disease and how they are regulated have yet to be clearly defined. The global regulator, CsrA, has been well characterized in several bacterial genera and is known to regulate a number of independent pathways via a post transcriptional mechanism, but remains relatively uncharacterized in the genus Campylobacter. Previously, we reported data illustrating the requirement for CsrA in several virulence related phenotypes of C. jejuni strain 81–176, indicating that the Csr pathway is important for Campylobacter pathogenesis. Results We compared the Escherichia coli and C. jejuni orthologs of CsrA and characterized the ability of the C. jejuni CsrA protein to functionally complement an E. coli csrA mutant. Phylogenetic comparison of E. coli CsrA to orthologs from several pathogenic bacteria demonstrated variability in C. jejuni CsrA relative to the known RNA binding domains of E. coli CsrA and in several amino acids reported to be involved in E. coli CsrA-mediated gene regulation. When expressed in an E. coli csrA mutant, C. jejuni CsrA succeeded in recovering defects in motility, biofilm formation, and cellular morphology; however, it failed to return excess glycogen accumulation to wild type levels. Conclusions These findings suggest that C. jejuni CsrA is capable of efficiently binding some E. coli CsrA binding sites, but not others, and provide insight into the biochemistry of C. jejuni CsrA. PMID:23051923

  20. A low-fat, whole-food vegan diet, as well as other strategies that down-regulate IGF-I activity, may slow the human aging process.

    Science.gov (United States)

    McCarty, Mark F

    2003-06-01

    A considerable amount of evidence is consistent with the proposition that systemic IGF-I activity acts as pacesetter in the aging process. A reduction in IGF-I activity is the common characteristic of rodents whose maximal lifespan has been increased by a wide range of genetic or dietary measures, including caloric restriction. The lifespans of breeds of dogs and strains of rats tend to be inversely proportional to their mature weight and IGF-I levels. The link between IGF-I and aging appears to be evolutionarily conserved; in worms and flies, lifespan is increased by reduction-of-function mutations in signaling intermediates homologous to those which mediate insulin/IGF-I activity in mammals. The fact that an increase in IGF-I activity plays a key role in the induction of sexual maturity, is consistent with a broader role for-IGF-I in aging regulation. If down-regulation of IGF-I activity could indeed slow aging in humans, a range of practical measures for achieving this may be at hand. These include a low-fat, whole-food, vegan diet, exercise training, soluble fiber, insulin sensitizers, appetite suppressants, and agents such as flax lignans, oral estrogen, or tamoxifen that decrease hepatic synthesis of IGF-I. Many of these measures would also be expected to decrease risk for common age-related diseases. Regimens combining several of these approaches might have a sufficient impact on IGF-I activity to achieve a useful retardation of the aging process. However, in light of the fact that IGF-I promotes endothelial production of nitric oxide and may be of especial importance to cerebrovascular health, additional measures for stroke prevention-most notably salt restriction-may be advisable when attempting to down-regulate IGF-I activity as a pro-longevity strategy.

  1. The lipid-sensor candidates CD36 and GPR120 are differentially regulated by dietary lipids in mouse taste buds: impact on spontaneous fat preference.

    Directory of Open Access Journals (Sweden)

    Céline Martin

    Full Text Available BACKGROUND: Recent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s played by these gustatory lipid-sensor candidates. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of biochemical, nutritional and behavioural studies in wild-type, CD36(+/-and CD36(-/- mice, it was found that: 1° CD36 and GPR120 display different diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being down-regulated during the dark period in contrast to GPR120, 2° this change is due to food intake and strictly dependent of the presence of lipids in the diet, 3° CD36 protein levels are also rapidly but transiently decreased by the food intake, a two-fold drop in CD36 protein levels being found 1 h after refeeding, followed by a progressive return to the pre-prandial values, 4° this down-regulation, which has a post-transcriptional origin, seems sufficient to alter the spontaneous fat preference, independently to change in the GPR120 gene expression. CONCLUSIONS/SIGNIFICANCE: In contrast to GPR120, CD36 appears to be a food-sensitive lipid sensor in the gustatory circumvallate papillae. Lipid-mediated change in lingual CD36 expression might modulate the motivation for fat during a meal, initially high and then gradually decreasing secondary to the food intake. This short-term lipid-mediated effect is reminiscent of sensory-specific satiety. These findings, which highlight the role played by CD36 in the oro-sensory perception of dietary lipids, raise the possibility of novel pharmacological strategies to modify attraction for fatty foods and decrease obesity risks.

  2. Ribonuclease-mediated control of body fat

    DEFF Research Database (Denmark)

    Habacher, Cornelia; Guo, Yanwu; Venz, Richard

    2016-01-01

    . Using exon-intron split analysis, we find that REGE-1 promotes fat by degrading the mRNA encoding ETS-4, a fat-loss-promoting transcription factor. Because ETS-4, in turn, induces rege-1 transcription, REGE-1 and ETS-4 appear to form an auto-regulatory module. We propose that this type of fat regulation...

  3. A WRKY transcription factor from Withania somnifera regulates triterpenoid withanolide accumulation and biotic stress tolerance through modulation of phytosterol and defense pathways.

    Science.gov (United States)

    Singh, Anup Kumar; Kumar, Sarma Rajeev; Dwivedi, Varun; Rai, Avanish; Pal, Shaifali; Shasany, Ajit K; Nagegowda, Dinesh A

    2017-08-01

    Withania somnifera produces pharmacologically important triterpenoid withanolides that are derived via phytosterol pathway; however, their biosynthesis and regulation remain to be elucidated. A jasmonate- and salicin-inducible WRKY transcription factor from W. somnifera (WsWRKY1) exhibiting correlation with withaferin A accumulation was functionally characterized employing virus-induced gene silencing and overexpression studies combined with transcript and metabolite analyses, and chromatin immunoprecipitation assay. WsWRKY1 silencing resulted in stunted plant growth, reduced transcripts of phytosterol pathway genes with corresponding reduction in phytosterols and withanolides in W. somnifera. Its overexpression elevated the biosynthesis of triterpenoids in W. somnifera (phytosterols and withanolides), as well as tobacco and tomato (phytosterols). Moreover, WsWRKY1 binds to W-box sequences in promoters of W. somnifera genes encoding squalene synthase and squalene epoxidase, indicating its direct regulation of triterpenoid pathway. Furthermore, while WsWRKY1 silencing in W. somnifera compromised the tolerance to bacterial growth, fungal infection, and insect feeding, its overexpression in tobacco led to improved biotic stress tolerance. Together these findings demonstrate that WsWRKY1 has a positive regulatory role on phytosterol and withanolides biosynthesis, and defense against biotic stress, highlighting its importance as a metabolic engineering tool for simultaneous improvement of triterpenoid biosynthesis and plant defense. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  4. Premigratory fat metabolism in hummingbirds: A rumsfeldian approach

    Directory of Open Access Journals (Sweden)

    Raul K. SUAREZ

    2013-06-01

    Full Text Available Hummingbird migration is a remarkable feat, given the small body sizes of migratory species, their high metabolic rates during flight and the long distances traveled using fat to fuel the effort. Equally remarkable is the ability of premigratory hummingbirds in the wild to accumulate fat, synthesized from sugar, at rates as high as 10% of body mass per day. This paper summarizes, using Rumsfeldian terminology, “known knowns” concerning the energetics of hummingbird migration and premigratory fattening. Energy metabolism during hover-feeding on floral nectar is fueled directly by dietary sugar through the pathway recently named the “sugar oxidation cascade”. However, flight without feeding for more than a few minutes requires shifting to fat as a fuel. It is proposed that behavior and metabolic fuel choice are coadapted to maximize the rate of fat deposition during premigratory fattening. The hummingbird liver appears to possess extraordinarily high capacities for fatty acid synthesis. The analysis of “known knowns” leads to identification of “known unknowns”, e.g., the fates of dietary glucose and fructose, the regulation of fat metabolism and metabolic interactions between liver and adipose tissue. The history of science behooves recognition of “unknown unknowns” that, when discovered serendipitously, might shed new light on fundamental mechanisms as well as human pathological conditions [Current Zoology 59 (3: 371–380, 2013].

  5. Association of fat mass and obesity-associated and retinitis pigmentosa guanosine triphosphatase (GTPase) regulator-interacting protein-1 like polymorphisms with body mass index in Chinese women.

    Science.gov (United States)

    Chen, Boyu; Li, Zhiqiang; Chen, Jianhua; Ji, Jue; Shen, Jingyi; Xu, Yufeng; Zhao, Yingying; Liu, Danping; Shen, Yinhuan; Zhang, Weijie; Shen, Jiawei; Wang, Yonggang; Shi, Yongyong

    2018-04-14

    Body mass index (BMI) is the most commonly used quantitative measure of adiposity. It is a kind of complex genetic diseases which are caused by multiple susceptibility genes. The first intron of fat mass and obesity-associated (FTO) has been widely discovered to be associated with BMI. Retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) is located in the upstream region of FTO and has been proved to be linked with obesity through functional tests. We carried out a genetic association analysis to figure out the role of the FTO gene and the RPGRIP1L gene in BMI. A quantitative traits study with 6,102 Chinese female samples, adjusted for age, was performed during our project. Among the twelve SNPs, rs1421085, rs1558902, rs17817449, rs8050136, rs9939609, rs7202296, rs56137030, rs9930506 and rs12149832 in the FTO gene were significantly associated with BMI after Bonferroni correction. Meanwhile, rs9934800 in the RPGRIP1L gene showed significance with BMI before Bonferroni correction, but this association was eliminated after Bonferroni correction. Our results suggested that genetic variants in the FTO gene were strongly associated with BMI in Chinese women, which may serve as targets of pharmaceutical research and development concerning BMI. Meanwhile, we didn't found the significant association between RPGRIP1L and BMI in Chinese women.

  6. Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat

    Directory of Open Access Journals (Sweden)

    Shiki Okamoto

    2018-01-01

    Full Text Available Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD and a high-fat diet (HFD remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH-positive neurons in the rostral region of the paraventricular hypothalamus (PVH induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism. These neurons manifest activation of AMP-activated protein kinase (AMPK during food deprivation, and this activation is necessary and sufficient for selection of an HCD over an HFD. Furthermore, this effect is mediated by carnitine palmitoyltransferase 1c (CPT1c. Thus, our results identify the specific neurons and intracellular signaling pathway responsible for regulation of the complex behavior of selection between an HCD and an HFD.

  7. IL-13 promotes collagen accumulation in Crohn's disease fibrosis by down-regulation of fibroblast MMP synthesis: a role for innate lymphoid cells?

    Directory of Open Access Journals (Sweden)

    Jennifer R Bailey

    Full Text Available BACKGROUND: Fibrosis is a serious consequence of Crohn's disease (CD, often necessitating surgical resection. We examined the hypothesis that IL-13 may promote collagen accumulation within the CD muscle microenvironment. METHODS: Factors potentially modulating collagen deposition were examined in intestinal tissue samples from fibrotic (f CD and compared with cancer control (C, ulcerative colitis (UC and uninvolved (u CD. Mechanisms attributable to IL-13 were analysed using cell lines derived from uninvolved muscle tissue and tissue explants. RESULTS: In fCD muscle extracts, collagen synthesis was significantly increased compared to other groups, but MMP-2 was not co-ordinately increased. IL-13 transcripts were highest in fCD muscle compared to muscle from other groups. IL-13 receptor (R α1 was expressed by intestinal muscle smooth muscle, nerve and KIR(+ cells. Fibroblasts from intestinal muscle expressed Rα1, phosphorylated STAT6 in response to IL-13, and subsequently down-regulated MMP-2 and TNF-α-induced MMP-1 and MMP-9 synthesis. Cells with the phenotype KIR(+CD45(+CD56(+/-CD3(- were significantly increased in fCD muscle compared to all other groups, expressed Rα1 and membrane IL-13, and transcribed high levels of IL-13. In explanted CD muscle, these cells did not phosphorylate STAT6 in response to exogenous IL-13. CONCLUSIONS: The data indicate that in fibrotic intestinal muscle of Crohn's patients, the IL-13 pathway is stimulated, involving a novel population of infiltrating IL-13Rα1(+, KIR(+ innate lymphoid cells, producing IL-13 which inhibits fibroblast MMP synthesis. Consequently, matrix degradation is down-regulated and this leads to excessive collagen deposition.

  8. Dual regulation of root hydraulic conductivity and plasma membrane aquaporins by plant nitrate accumulation and high-affinity nitrate transporter NRT2.1.

    Science.gov (United States)

    Li, Guowei; Tillard, Pascal; Gojon, Alain; Maurel, Christophe

    2016-04-01

    The water status and mineral nutrition of plants critically determine their growth and development. Nitrate (NO3(-)), the primary nitrogen source of higher plants, is known to impact the water transport capacity of roots (root hydraulic conductivity, Lpr). To explore the effects and mode of action of NO3(-) on Lpr, we used an extended set of NO3(-) transport (nrt1.1, nrt1.2, nrt1.5 and nrt2.1), signaling (nrt1.1 and nrt2.1) and metabolism (nia) mutants in Arabidopsis, grown under various NO3(-) conditions. First, a strong positive relationship between Lpr and NO3(-) accumulation, in shoots rather than in roots, was revealed. Secondly, a specific 30% reduction of Lpr in nrt2.1 plants unraveled a major role for the high-affinity NO3(-) transporter NRT2.1 in increasing Lpr These results indicate that NO3(-)signaling rather than nitrogen assimilation products governs Lpr in Arabidopsis. Quantitative real-time reverse transcription-PCR and enzyme-linked immunosorbent assays (ELISAs) were used to investigate the effects of NO3(-) availability on plasma membrane aquaporin (plasma membrane intrinsic protein; PIP) expression. Whereas PIP regulation mostly occurs at the post-translational level in wild-type plants, a regulation of PIPs at both the transcriptional and translational levels was uncovered in nrt2.1 plants. In conclusion, this work reveals that control of Arabidopsis Lpr and PIP functions by NO3(-) involves novel shoot to root signaling and NRT2.1-dependent functions. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation.

    Science.gov (United States)

    Hao, Wu; Tashiro, Syoichi; Hasegawa, Tomoka; Sato, Yuiko; Kobayashi, Tami; Tando, Toshimi; Katsuyama, Eri; Fujie, Atsuhiro; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Amizuka, Norio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-07-10

    Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination, and all conditions were significantly rescued by aldose reductase inhibitor or vitamin D3 administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation*

    Science.gov (United States)

    Hao, Wu; Tashiro, Syoichi; Hasegawa, Tomoka; Sato, Yuiko; Kobayashi, Tami; Tando, Toshimi; Katsuyama, Eri; Fujie, Atsuhiro; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Amizuka, Norio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-01-01

    Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination, and all conditions were significantly rescued by aldose reductase inhibitor or vitamin D3 administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition. PMID:25998127

  11. Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change.

    Science.gov (United States)

    Rinnankoski-Tuikka, Rita; Hulmi, Juha J; Torvinen, Sira; Silvennoinen, Mika; Lehti, Maarit; Kivelä, Riikka; Reunanen, Hilkka; Kujala, Urho M; Kainulainen, Heikki

    2014-08-01

    The relation between lipid accumulation and influence of exercise on insulin sensitivity is not straightforward. A proper balance between lipid droplet synthesis, lipolysis, and oxidative metabolism would ensure low local intramyocellular fatty acid levels, thereby possibly protecting against lipotoxicity-associated insulin resistance. This study investigated whether the accumulation of triglycerides and lipid droplets in response to high availability of fatty acids after high-fat feeding would parallel the abundance of intramyocellular perilipin proteins, especially PLIN5. The effects on these variables after diet change or voluntary running exercise intervention in skeletal muscle were also investigated. During a 19-week experiment, C57BL/6J mice were studied in six different groups: low-fat diet sedentary, low-fat diet active, high-fat diet sedentary, high-fat diet active and two groups which were high-fat sedentary for nine weeks, after which divided into low-fat sedentary or low-fat active groups. Myocellular triglyceride concentration and perilipin protein expression levels were assessed. We show that, concurrently with impaired insulin sensitivity, the expression level of PLIN5 and muscular triglyceride concentration increased dramatically after high-fat diet. These adaptations were reversible after the diet change intervention with no additional effect of exercise. After high-fat diet, lipid droplets become larger providing more surface area for PLIN5. We suggest that PLIN5 is an important regulator of lipid droplet turnover in altered conditions of fatty acid supply and consumption. Imbalances in lipid droplet metabolism and turnover might lead to lipotoxicity-related insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The Arabidopsis Mitochondrial Protease FtSH4 Is Involved in Leaf Senescence via Regulation of WRKY-Dependent Salicylic Acid Accumulation and Signaling.

    Science.gov (United States)

    Zhang, Shengchun; Li, Cui; Wang, Rui; Chen, Yaxue; Shu, Si; Huang, Ruihua; Zhang, Daowei; Li, Jian; Xiao, Shi; Yao, Nan; Yang, Chengwei

    2017-04-01

    Mitochondria and autophagy play important roles in the networks that regulate plant leaf senescence and cell death. However, the molecular mechanisms underlying the interactions between mitochondrial signaling and autophagy are currently not well understood. This study characterized the function of the Arabidopsis ( Arabidopsis thaliana ) mitochondrial AAA-protease gene FtSH4 in regulating autophagy and senescence, finding that FtSH4 mediates WRKY-dependent salicylic acid (SA) accumulation and signaling. Knockout of FtSH4 in the ftsh4-4 mutant resulted in severe leaf senescence, cell death, and high autophagy levels. The level of SA increased dramatically in the ftsh4-4 mutant. Expression of nahG in the ftsh4-4 mutant led to decreased SA levels and suppressed the leaf senescence and cell death phenotypes. The transcript levels of several SA synthesis and signaling genes, including SALICYLIC ACID INDUCTION DEFICIENT2 ( SID2 ), NON-RACE-SPECIFIC DISEASE RESISTANCE1 ( NDR1 ), and NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 ( NPR1 ), increased significantly in the ftsh4-4 mutants compared with the wild type. Loss of function of SID2 , NDR1 , or NPR1 in the ftsh4-4 mutant reversed the ftsh4-4 senescence and autophagy phenotypes. Furthermore, ftsh4-4 mutants had elevated levels of transcripts of several WRKY genes, including WRKY40 , WRKY46 , WRKY51 , WRKY60 , WRKY63 , and WRKY75 ; all of these WRKY proteins can bind to the promoter of SID2 Loss of function of WRKY75 in the ftsh4-4 mutants decreased the levels of SA and reversed the senescence phenotype. Taken together, these results suggest that the mitochondrial ATP-dependent protease FtSH4 may regulate the expression of WRKY genes by modifying the level of reactive oxygen species and the WRKY transcription factors that control SA synthesis and signaling in autophagy and senescence. © 2017 American Society of Plant Biologists. All Rights Reserved.

  13. Fat storage-inducing transmembrane protein 2 is required for normal fat storage in adipose tissue.

    Science.gov (United States)

    Miranda, Diego A; Kim, Ji-Hyun; Nguyen, Long N; Cheng, Wang; Tan, Bryan C; Goh, Vera J; Tan, Jolene S Y; Yaligar, Jadegoud; Kn, Bhanu Prakash; Velan, S Sendhil; Wang, Hongyan; Silver, David L

    2014-04-04

    Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo.

  14. The animal fat paradox and meat quality.

    Science.gov (United States)

    Webb, E C; O'Neill, H A

    2008-09-01

    The purpose of this paper is to address some of the paradoxical issues and perceptions regarding animal fats and the related effects on meat quality and consumer perceptions. Meat scientists have been studying carcass characteristics for many years and although the factors that influence the accumulation, distribution and composition of carcass fat in livestock have been extensively researched, the role, value and perceptions of animal fats in meat quality differ significantly in importance between producers, abattoirs, butchers, retailers and consumers. Fat and long-chain fatty acids, whether in adipose tissue or muscle, contribute to important aspects of meat quality and are central to the nutritional and sensory values of meat. In this review the nutritional value of fat, as well as the importance of fat in terms of carcass and meat quality will be highlighted. The 'quality' of meat depends greatly on the socio-demographic backgrounds of the consumer. The aim is to focus on the global importance of fat in the carcass to the producer, processor and consumer. There is currently no clear cut definition for fat quality because the acceptability and perceived quality of fat varies significantly in terms of quantity, colour, consistency and chemical composition in different species of livestock around the world. The association between animal fats and human health is critical and recommendations by health professionals range from excluding fats altogether to a moderate consumption of fats due to their essential role in the body. Recently the emphasis has shifted away from fat quantity to fat quality. Despite these recommendations and years of bad publicity in terms of the adverse affects of animal fats in human health, the livestock industry seems reluctant to shift its focus to fat quality rather than quantity. This approach may adversely affect future meat consumption by consumers who are becoming increasingly critical about the food they eat.

  15. Bioactive Lipids in Dairy Fat

    DEFF Research Database (Denmark)

    Hellgren, Lars; Nordby, Pernille

    2017-01-01

    Milk fat is the most important energy source for the newborn infant beside its important role as energy source, milk fat also contain a range of bioactive lipids, that potentially can modulate the immune response and metabolic regulation in the child. In this chapter we review the literature on b...... on bioactive dairy fatty acids: conjugated linoleic acid, branched chained and odd chained fatty acids, as well as bioactive complex lipids such as sphingomyelin and gangliosides....

  16. Plastids and Carotenoid Accumulation.

    Science.gov (United States)

    Li, Li; Yuan, Hui; Zeng, Yunliu; Xu, Qiang

    Plastids are ubiquitously present in plants and are the organelles for carotenoid biosynthesis and storage. Based on their morphology and function, plastids are classified into various types, i.e. proplastids, etioplasts, chloroplasts, amyloplasts, and chromoplasts. All plastids, except proplastids, can synthesize carotenoids. However, plastid types have a profound effect on carotenoid accumulation and stability. In this chapter, we discuss carotenoid biosynthesis and regulation in various plastids with a focus on carotenoids in chromoplasts. Plastid transition related to carotenoid biosynthesis and the different capacity of various plastids to sequester carotenoids and the associated effect on carotenoid stability are described in light of carotenoid accumulation in plants.

  17. TaMYB13-1, a R2R3 MYB transcription factor, regulates the fructan synthetic pathway and contributes to enhanced fructan accumulation in bread wheat

    Science.gov (United States)

    Kooiker, Maarten; Drenth, Janneke; Glassop, Donna; McIntyre, C. Lynne; Xue, Gang-Ping

    2013-01-01

    Fructans are the major component of temporary carbon reserve in the stem of temperate cereals, which is used for grain filling. Three families of fructosyltransferases are directly involved in fructan synthesis in the vacuole of Triticum aestivum. The regulatory network of the fructan synthetic pathway is largely unknown. Recently, a sucrose-upregulated wheat MYB transcription factor (TaMYB13-1) was shown to be capable of activating the promoter activities of sucrose:sucrose 1-fructosyltransferase (1-SST) and sucrose:fructan 6-fructosyltransferase (6-SFT) in transient transactivation assays. This work investigated TaMYB13-1 target genes and their influence on fructan synthesis in transgenic wheat. TaMYB13-1 overexpression resulted in upregulation of all three families of fructosyltransferases including fructan:fructan 1-fructosyltransferase (1-FFT). A γ-vacuolar processing enzyme (γ-VPE1), potentially involved in processing the maturation of fructosyltransferases in the vacuole, was also upregulated by TaMYB13-1 overexpression. Multiple TaMYB13 DNA-binding motifs were identified in the Ta1-FFT1 and Taγ-VPE1 promoters and were bound strongly by TaMYB13-1. The expression profiles of these target genes and TaMYB13-1 were highly correlated in recombinant inbred lines and during stem development as well as the transgenic and non-transgenic wheat dataset, further supporting a direct regulation of these genes by TaMYB13-1. TaMYB13-1 overexpression in wheat led to enhanced fructan accumulation in the leaves and stems and also increased spike weight and grain weight per spike in transgenic plants under water-limited conditions. These data suggest that TaMYB13-1 plays an important role in coordinated upregulation of genes necessary for fructan synthesis and can be used as a molecular tool to improve the high fructan trait. PMID:23873993

  18. INCREASED FAT INTAKE MAY STABILIZED CKD PROGRESSION IN LOW-FAT INTAKE PATIENTS

    Directory of Open Access Journals (Sweden)

    Min-Yu Chang

    2012-06-01

    Inadequate calories intake will induce excessive protein catabolism, which can cause accumulation of uremic toxins and acceleration of renal failure. Increasing fats intake is an easy way to achieve adequate calories acquirement and may stabilize the progression of CKD especially in low-fat intake patients.

  19. Multiple layers of temporal and spatial control regulate accumulation of the fruiting body-specific protein APP in Sordaria macrospora and Neurospora crassa.

    Science.gov (United States)

    Nowrousian, Minou; Piotrowski, Markus; Kück, Ulrich

    2007-07-01

    During fungal fruiting body development, specialized cell types differentiate from vegetative mycelium. We have isolated a protein from the ascomycete Sordaria macrospora that is not present during vegetative growth but accumulates in perithecia. The protein was sequenced by mass spectrometry and the corresponding gene was termed app (abundant perithecial protein). app transcript occurs only after the onset of sexual development; however, the formation of ascospores is not a prerequisite for APP accumulation. The transcript of the Neurospora crassa ortholog is present prior to fertilization, but the protein accumulates only after fertilization. In crosses of N. crassa Deltaapp strains with the wild type, APP accumulates when the wild type serves as female parent, but not in the reciprocal cross; thus, the presence of a functional female app allele is necessary and sufficient for APP accumulation. These findings highlight multiple layers of temporal and spatial control of gene expression during fungal development.

  20. Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets

    Directory of Open Access Journals (Sweden)

    Sunhye Shin

    2018-02-01

    Full Text Available Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON or high-fat diets (HFD containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB, olive oil (oleic acid-rich oil; OO, safflower oil (linoleic acid-rich oil; SFO, or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo.

  1. Batteries and accumulators in France

    International Nuclear Information System (INIS)

    2012-12-01

    The present report gives an overview of the batteries and accumulators market in France in 2011 based on the data reported through ADEME's Register of Batteries and accumulators. In 2001, the French Environmental Agency, known as ADEME, implemented a follow-up of the batteries and accumulators market, creating the Observatory of batteries and accumulators (B and A). In 2010, ADEME created the National Register of producers of Batteries and Accumulators in the context of the implementation of the order issued on November 18, 2009. This is one of the four enforcement orders for the decree 2009-1139 issued on September 22, 2009, concerning batteries and accumulators put on the market and the disposal of waste batteries and accumulators, and which transposes the EU-Directive 2006/66/CE into French law. This Register follows the former Observatory for batteries and accumulators. This Register aims to record the producers on French territory and to collect the B and A producers and recycling companies' annual reporting: the regulation indeed requires that all B and A producers and recycling companies report annually on the Register the quantities of batteries and accumulators they put on the market, collect and treat. Based on this data analysis, ADEME issues an annual report allowing both the follow-up of the batteries and accumulators market in France and communication regarding the achievement of the collection and recovery objectives set by EU regulation. This booklet presents the situation in France in 2011

  2. Dietary fat intake, supplements, and weight loss

    Science.gov (United States)

    Dyck, D. J.

    2000-01-01

    Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been

  3. A buoyancy-based screen of Drosophila larvae for fat-storage mutants reveals a role for Sir2 in coupling fat storage to nutrient availability.

    Directory of Open Access Journals (Sweden)

    Tânia Reis

    2010-11-01

    Full Text Available Obesity has a strong genetic component, but few of the genes that predispose to obesity are known. Genetic screens in invertebrates have the potential to identify genes and pathways that regulate the levels of stored fat, many of which are likely to be conserved in humans. To facilitate such screens, we have developed a simple buoyancy-based screening method for identifying mutant Drosophila larvae with increased levels of stored fat. Using this approach, we have identified 66 genes that when mutated increase organismal fat levels. Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins. However, since mammalian sirtuins function in many tissues in different ways, it has been difficult to define their role in energy homeostasis accurately under normal feeding conditions. We show that knockdown of Sir2 in the larval fat body results in increased fat levels. Moreover, using genetic mosaics, we demonstrate that Sir2 restricts fat accumulation in individual cells of the fat body in a cell-autonomous manner. Consistent with this function, changes in the expression of metabolic enzymes in Sir2 mutants point to a shift away from catabolism. Surprisingly, although Sir2 is typically upregulated under conditions of starvation, Sir2 mutant larvae survive better than wild type under conditions of amino-acid starvation as long as sugars are provided. Our findings point to a Sir2-mediated pathway that activates a catabolic response to amino-acid starvation irrespective of the sugar content of the diet.

  4. Stressed-induced TMEM135 protein is part of a conserved genetic network involved in fat storage and longevity regulation in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Vernat J Exil

    2010-12-01

    Full Text Available Disorders of mitochondrial fat metabolism lead to sudden death in infants and children. Although survival is possible, the underlying molecular mechanisms which enable this outcome have not yet been clearly identified. Here we describe a conserved genetic network linking disorders of mitochondrial fat metabolism in mice to mechanisms of fat storage and survival in Caenorhabditis elegans (C. elegans. We have previously documented a mouse model of mitochondrial very-long chain acyl-CoA dehydrogenase (VLCAD deficiency. We originally reported that the mice survived birth, but, upon exposure to cold and fasting stresses, these mice developed cardiac dysfunction, which greatly reduced survival. We used cDNA microarrays to outline the induction of several markers of lipid metabolism in the heart at birth in surviving mice. We hypothesized that the induction of fat metabolism genes in the heart at birth is part of a regulatory feedback circuit that plays a critical role in survival. The present study uses a dual approach employing both C57BL/6 mice and the nematode, C. elegans, to focus on TMEM135, a conserved protein which we have found to be upregulated 4.3 (±0.14-fold in VLCAD-deficient mice at birth. Our studies have demonstrated that TMEM135 is highly expressed in mitochondria and in fat-loaded tissues in the mouse. Further, when fasting and cold stresses were introduced to mice, we observed 3.25 (±0.03- and 8.2 (±0.31-fold increases in TMEM135 expression in the heart, respectively. Additionally, we found that deletion of the tmem135 orthologue in C. elegans caused a 41.8% (±2.8% reduction in fat stores, a reduction in mitochondrial action potential and decreased longevity of the worm. In stark contrast, C. elegans transgenic animals overexpressing TMEM-135 exhibited increased longevity upon exposure to cold stress. Based on these results, we propose that TMEM135 integrates biological processes involving fat metabolism and energy expenditure in

  5. The Citrus transcription factor, CitERF13, regulates citric acid accumulation via a protein-protein interaction with the vacuolar proton pump, CitVHA-c4.

    Science.gov (United States)

    Li, Shao-jia; Yin, Xue-ren; Xie, Xiu-lan; Allan, Andrew C; Ge, Hang; Shen, Shu-ling; Chen, Kun-song

    2016-02-03

    Organic acids are essential to fruit flavor. The vacuolar H(+) transporting adenosine triphosphatase (V-ATPase) plays an important role in organic acid transport and accumulation. However, less is known of V-ATPase interacting proteins and their relationship with organic acid accumulation. The relationship between V-ATPase and citric acid was investigated, using the citrus tangerine varieties 'Ordinary Ponkan (OPK)' and an early maturing mutant 'Zaoshu Ponkan (ZPK)'. Five V-ATPase genes (CitVHA) were predicted as important to citric acid accumulation. Among the genes, CitVHA-c4 was observed, using a yeast two-hybrid screen, to interact at the protein level with an ethylene response factor, CitERF13. This was verified using bimolecular fluorescence complementation assays. A similar interaction was also observed between Arabidopsis AtERF017 (a CitERF13 homolog) and AtVHA-c4 (a CitVHA-c4 homolog). A synergistic effect on citric acid levels was observed between V-ATPase proteins and interacting ERFs when analyzed using transient over-expression in tobacco and Arabidopsis mutants. Furthermore, the transcript abundance of CitERF13 was concomitant with CitVHA-c4. CitERF13 or AtERF017 over-expression leads to significant citric acid accumulation. This accumulation was abolished in an AtVHA-c4 mutant background. ERF-VHA interactions appear to be involved in citric acid accumulation, which was observed in both citrus and Arabidopsis.

  6. Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

    Science.gov (United States)

    Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

    2012-01-01

    Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur. PMID:22276186

  7. Utilização de medidas antropométricas para a avaliação do acúmulo de gordura visceral The use of anthropometric measures to assess visceral fat accumulation

    Directory of Open Access Journals (Sweden)

    Ana Carolina Junqueira Vasques

    2010-02-01

    accurate and precise measurement of visceral fat. However, both are costly and inapplicable in routine clinical practice and epidemiological studies. Anthropometric parameters are an option for visceral fat assessment in these situations, since they are innocuous, easy to use and inexpensive. In this context, this work aimed to critically analyze studies that assessed anthropometric parameters as indicators of visceral fat. A bibliographic review of domestic and international articles found in the databases Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Scientific Electronic Library Online, Science Direct and Pubmed, published from 1947 to 2007 was done. Emphasis was given to anthropometric parameters, such as body mass index, waist circumference, waist-to-hip ratio and sagittal abdominal diameter.

  8. Facts about trans fats

    Science.gov (United States)

    Trans fat is a type of dietary fat . Of all the fats, trans fat is the worst for your health. Too much ... from solid margarine to soft margarine. Ask what type of fats foods are cooked in when you eat out ...

  9. Fat Quantification in the Abdomen.

    Science.gov (United States)

    Hong, Cheng William; Fazeli Dehkordy, Soudabeh; Hooker, Jonathan C; Hamilton, Gavin; Sirlin, Claude B

    2017-12-01

    Fatty liver disease is characterized histologically by hepatic steatosis, the abnormal accumulation of lipid in hepatocytes. It is classified into alcoholic fatty liver disease and nonalcoholic fatty liver disease, and is an increasingly important cause of chronic liver disease and cirrhosis. Assessing the severity of hepatic steatosis in these conditions is important for diagnostic and prognostic purposes, as hepatic steatosis is potentially reversible if diagnosed early. The criterion standard for assessing hepatic steatosis is liver biopsy, which is limited by sampling error, its invasive nature, and associated morbidity. As such, noninvasive imaging-based methods of assessing hepatic steatosis are needed. Ultrasound and computed tomography are able to suggest the presence of hepatic steatosis based on imaging features, but are unable to accurately quantify hepatic fat content. Since Dixon's seminal work in 1984, magnetic resonance imaging has been used to compute the signal fat fraction from chemical shift-encoded imaging, commonly implemented as out-of-phase and in-phase imaging. However, signal fat fraction is confounded by several factors that limit its accuracy and reproducibility. Recently, advanced chemical shift-encoded magnetic resonance imaging methods have been developed that address these confounders and are able to measure the proton density fat fraction, a standardized, accurate, and reproducible biomarker of fat content. The use of these methods in the liver, as well as in other abdominal organs such as the pancreas, adrenal glands, and adipose tissue will be discussed in this review.

  10. High maysin corn silk extract reduces body weight and fat deposition in C57BL/6J mice fed high-fat diets.

    Science.gov (United States)

    Lee, Eun Young; Kim, Sun Lim; Kang, Hyeon Jung; Kim, Myung Hwan; Ha, Ae Wha; Kim, Woo Kyoung

    2016-12-01

    The study was performed to investigate the effects and mechanisms of action of high maysin corn silk extract on body weight and fat deposition in experimental animals. A total of 30 male C57BL/6J mice, 4-weeks-old, were purchased and divided into three groups by weight using a randomized block design. The normal-fat (NF) group received 7% fat (diet weight basis), the high-fat (HF) group received 25% fat and 0.5% cholesterol, and the high-fat corn silk (HFCS) group received high-fat diet and high maysin corn silk extract at 100 mg/kg body weight through daily oral administration. Body weight and body fat were measured, and mRNA expression levels of proteins involved in adipocyte differentiation, fat accumulation, fat synthesis, lipolysis, and fat oxidation in adipose tissue and the liver were measured. After experimental diet intake for 8 weeks, body weight was significantly lower in the HFCS group compared to the HF group ( P corn silk extract inhibits expression of genes involved in adipocyte differentiation, fat accumulation, and fat synthesis as well as promotes expression of genes involved in lipolysis and fat oxidation, further inhibiting body fat accumulation and body weight elevation in experimental animals.

  11. The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites

    DEFF Research Database (Denmark)

    Jensen, Dorit P; Andersen, Mette K; Hansen, Lars

    2007-01-01

    Food intake and weight gain are influenced by endocannabinoids whose actions are regulated by the fatty acid amide hydrolase (FAAH) enzyme. The homozygous Thr/Thr genotype of the functional Pro129Thr variant (rs324420) in the gene encoding FAAH was recently reported to associate with overweight a...

  12. Transient Transcriptional Regulation of the CYS-C1 Gene and Cyanide Accumulation upon Pathogen Infection in the Plant Immune Response1[C][W

    Science.gov (United States)

    García, Irene; Rosas, Tábata; Bejarano, Eduardo R.; Gotor, Cecilia; Romero, Luis C.

    2013-01-01

    Cyanide is produced concomitantly with ethylene biosynthesis. Arabidopsis (Arabidopsis thaliana) detoxifies cyanide primarily through the enzyme β-cyanoalanine synthase, mainly by the mitochondrial CYS-C1. CYS-C1 loss of function is not toxic for the plant and leads to an increased level of cyanide in cys-c1 mutants as well as a root hairless phenotype. The classification of genes differentially expressed in cys-c1 and wild-type plants reveals that the high endogenous cyanide content of the cys-c1 mutant is correlated with the biotic stress response. Cyanide accumulation and CYS-C1 gene expression are negatively correlated during compatible and incompatible plant-bacteria interactions. In addition, cys-c1 plants present an increased susceptibility to the necrotrophic fungus Botrytis cinerea and an increased tolerance to the biotrophic Pseudomonas syringae pv tomato DC3000 bacterium and Beet curly top virus. The cys-c1 mutation produces a reduction in respiration rate in leaves, an accumulation of reactive oxygen species, and an induction of the alternative oxidase AOX1a and pathogenesis-related PR1 expression. We hypothesize that cyanide, which is transiently accumulated during avirulent bacterial infection and constitutively accumulated in the cys-c1 mutant, uncouples the respiratory electron chain dependent on the cytochrome c oxidase, and this uncoupling induces the alternative oxidase activity and the accumulation of reactive oxygen species, which act by stimulating the salicylic acid-dependent signaling pathway of the plant immune system. PMID:23784464

  13. Up-regulated Ectonucleotidases in Fas-Associated Death Domain Protein- and Receptor-Interacting Protein Kinase 1-Deficient Jurkat Leukemia Cells Counteract Extracellular ATP/AMP Accumulation via Pannexin-1 Channels during Chemotherapeutic Drug-Induced Apoptosis.

    Science.gov (United States)

    Boyd-Tressler, Andrea M; Lane, Graham S; Dubyak, George R

    2017-07-01

    Pannexin-1 (Panx1) channels mediate the efflux of ATP and AMP from cancer cells in response to induction of extrinsic apoptosis by death receptors or intrinsic apoptosis by chemotherapeutic agents. We previously described the accumulation of extracellular ATP /AMP during chemotherapy-induced apoptosis in Jurkat human leukemia cells. In this study, we compared how different signaling pathways determine extracellular nucleotide pools in control Jurkat cells versus Jurkat lines that lack the Fas-associated death domain (FADD) or receptor-interacting protein kinase 1 (RIP1) cell death regulatory proteins. Tumor necrosis factor- α induced extrinsic apoptosis in control Jurkat cells and necroptosis in FADD-deficient cells; treatment of both lines with chemotherapeutic drugs elicited similar intrinsic apoptosis. Robust extracellular ATP/AMP accumulation was observed in the FADD-deficient cells during necroptosis, but not during apoptotic activation of Panx1 channels. Accumulation of extracellular ATP/AMP was similarly absent in RIP1-deficient Jurkat cells during apoptotic responses to chemotherapeutic agents. Apoptotic activation triggered equivalent proteolytic gating of Panx1 channels in all three Jurkat cell lines. The differences in extracellular ATP/AMP accumulation correlated with cell-line-specific expression of ectonucleotidases that metabolized the released ATP/AMP. CD73 mRNA, and α β -methylene-ADP-inhibitable ecto-AMPase activity were elevated in the FADD-deficient cells. In contrast, the RIP1-deficient cells were defined by increased expression of tartrate-sensitive prostatic acid phosphatase as a broadly acting ectonucleotidase. Thus, extracellular nucleotide accumulation during regulated tumor cell death involves interplay between ATP/AMP efflux pathways and different cell-autonomous ectonucleotidases. Differential expression of particular ectonucleotidases in tumor cell variants will determine whether chemotherapy-induced activation of Panx1 channels

  14. Quantification of Liver Fat with Magnetic Resonance Imaging

    Science.gov (United States)

    Reeder, Scott B.; Sirlin, Claude

    2010-01-01

    Intracellular fat accumulation is common feature of liver disease. Intracellular fat (steatosis) is the histological hallmark of non-alcoholic fatty liver disease (NAFLD) but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This article reviews emerging magnetic resonance imaging techniques that attempt to quantify liver fat. The content provides an overview of fatty liver disease and diseases where fat is an important disease feature. Also discussed is the current use and limitation of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat would be beneficial. PMID:21094444

  15. [Legal Framework of Autologous Fat Usage in Point-of-Care Treatments in Plastic and Aesthetic Surgery - Risks of Criminal Prosecution and Infringement of Medical Law Due to Pharmaceutical Regulations].

    Science.gov (United States)

    Faltus, T

    2016-08-01

    The use of autologous fat, especially for (stem) cell-assisted lipotransfer in plastic and aesthetic surgery, has regularly been regarded as the manufacture and application of so called Advanced Therapy Medicinal Products (ATMP). However, the in-house production of such pharmaceuticals at the point-of-care (PoC) in the surgeon's practice is not permitted without an official manufacturing license. Therefore, before beginning such treatments, a pharmaceutical manufacturing license has to be granted to the surgeon to avoid criminal prosecution and negative consequences due to infringement of professional regulations. Because such a license is linked to compliance with GMP standard, in-house manufacturing of such pharmaceuticals also implies extra technical and personnel expenses. The surgeon is obliged to check that the available autologous fat based applications are in compliance with pharmaceutical legislation. Repeated infringements of pharmaceutical regulations are incompatible with medical reliability - a prerequisite for the license to practice medicine. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Carbohydrates as Fat Replacers.

    Science.gov (United States)

    Peng, Xingyun; Yao, Yuan

    2017-02-28

    The overconsumption of dietary fat contributes to various chronic diseases, which encourages attempts to develop and consume low-fat foods. Simple fat reduction causes quality losses that impede the acceptance of foods. Fat replacers are utilized to minimize the quality deterioration after fat reduction or removal to achieve low-calorie, low-fat claims. In this review, the forms of fats and their functions in contributing to food textural and sensory qualities are discussed in various food systems. The connections between fat reduction and quality loss are described in order to clarify the rationales of fat replacement. Carbohydrate fat replacers usually have low calorie density and provide gelling, thickening, stabilizing, and other texture-modifying properties. In this review, carbohydrates, including starches, maltodextrins, polydextrose, gums, and fibers, are discussed with regard to their interactions with other components in foods as well as their performances as fat replacers in various systems.

  17. Scientific Opinion on the substantiation of a health claim related to fat-free yogurts and fermented milks with live yogurt cultures complying with the specifications ?fat free?, ?low in sugars?, ?high protein?, ?source of calcium? and ?source of vitamin D? for nutrition claims and maintenance of lean body mass in the context of an energy-restricted diet pursuant to Article 13.5 of Regulation (EC) No 1924/2006

    OpenAIRE

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)

    2015-01-01

    Following an application from Federación Nacional de Industrias Lácteas (FeNIL), submitted pursuant to Article 13.5 of Regulation (EC) No 1924/2006 via the Competent Authority of Spain, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to fat-free yogurts and fermented milks with live yogurt cultures complying with the specifications “fat free”, “low in sugars”, “high protein”, “source of ca...

  18. Bone and fat connection in aging bone.

    Science.gov (United States)

    Duque, Gustavo

    2008-07-01

    The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

  19. Sterol-mediated regulation of mevalonic acid synthesis. Accumulation of 4-carboxysterols as the predominant sterols synthesized in a Chinese hamster ovary cell cholesterol auxotroph (mutant 215)

    International Nuclear Information System (INIS)

    Plemenitas, A.; Havel, C.M.; Watson, J.A.

    1990-01-01

    Chinese hamster ovary-215 (CHO-215) mutant cells are auxotrophic for cholesterol. Berry and Chang (Berry, D. J., and Chang, T. Y. (1982) Biochemistry 21, 573-580) suggested that the metabolic lesion was at the level of 4-methyl sterol oxidation. However, the observed cellular accumulation of lanosterol was not consistent with a defect at this metabolic site. With the use of a novel Silica Sep Pak sterol separation procedure, we demonstrated that 60-80% of the acetonesoluble lipid radioactivity in [5-3H]mevalonate-labeled CHO-215 cells was incorporated into acidic sterols. 7(8),Cholesten-4 beta-methyl,4 alpha-carboxy,3 beta-ol was the dominant end product. In addition to this acidic sterol, 7(8),24-cholestadien,4 beta-methyl,4 alpha-carboxy,3 beta-ol and 7(8),24-cholestadien,4 alpha-carboxy,3 beta-ol were also isolated. Incubation of cell-free extracts with [3H]7(8)-cholesten-4 beta-methyl, 4 alpha-carboxy,3 beta-ol and pyridine nucleotides confirmed that CHO-215 4-carboxysterol decarboxylase activity was less than 1% of that for wild type cells. Thus, a correspondence between decreased 4-carboxysterol decarboxylase activity and the spectrum of accumulated sterol products by intact CHO-215 cells was demonstrated. No detectable cholesterol was synthesized by CHO-215 cells. 3H-Product accumulation studies demonstrated that 7(8),24-cholestadien, 4 beta-methyl,4 alpha-carboxy,3 beta-ol increased prior to its subsequent saturation at the delta 24 carbon. Furthermore, the steady state ratio for delta 24-saturated acidic sterols/unsaturated acidic sterols was dependent on media cholesterol source and amount. Finally, the accumulated acidic sterol(s) were not regulatory signal molecules for the modulation of 3-hydroxy-3-methyl-glutaryl coenzyme. A reductase activity in response to cholesterol availability

  20. A new tomato NAC (NAM/ATAF1/2/CUC2) transcription factor, SlNAC4, functions as a positive regulator of fruit ripening and carotenoid accumulation.

    Science.gov (United States)

    Zhu, Mingku; Chen, Guoping; Zhou, Shuang; Tu, Yun; Wang, Yi; Dong, Tingting; Hu, Zongli

    2014-01-01

    Fruit ripening in tomato (Solanum lycopersicum) is a complicated development process affected by both endogenous hormonal and genetic regulators and external signals. Although the role of NOR, a member of the NAC domain family, in mediating tomato fruit ripening has been established, its underlying molecular mechanisms remain unclear. To explore further the role of NAC transcription factors in fruit ripening, we characterized a new tomato NAC domain protein, named SlNAC4, which shows high accumulation in sepal and at the onset of fruit ripening. Various stress treatments including wounding, NaCl, dehydration and low temperature significantly increased the expression of SlNAC4. Reduced expression of SlNAC4 by RNA interference (RNAi) in tomato resulted in delayed fruit ripening, suppressed Chl breakdown and decreased ethylene synthesis mediated mainly through reduced expression of ethylene biosynthesis genes of system-2, and reduced carotenoids by alteration of the carotenoid pathway flux. Transgenic tomato fruits also displayed significant down-regulation of multiple ripening-associated genes, indicating that SlNAC4 functions as a positive regulator of fruit ripening by affecting ethylene synthesis and carotenoid accumulation. Moreover, we also noted that SlNAC4 could not be induced by ethylene and may function upstream of the ripening regulator RIN and positively regulate its expression. Yeast two-hybrid assay further revealed that SlNAC4 could interact with both RIN and NOR protein. These results suggested that ethylene-dependent and -independent processes are regulated by SlNAC4 in the fruit ripening regulatory network.

  1. Dietary salecan reverts partially the metabolic gene expressions and NMR-based metabolomic profiles from high-fat-diet-induced obese rats.

    Science.gov (United States)

    Sun, Qi; Li, Minghui; Yang, Xiao; Xu, Xi; Wang, Junsong; Zhang, Jianfa

    2017-09-01

    Previous studies suggest that dietary salecan (a water-soluble β-glucan) effectively reduces high-fat-diet-induced adiposity through disturbing bile-acid-promoted emulsification in mice. However, the effects of salecan on metabolic genes and metabolites involved in lipid accumulation are mostly unknown. Here, we confirmed that dietary 3% and 6% salecan for 4 weeks markedly decreased fat accumulation in liver and adipose tissue in high-fat-diet rats, displaying a decrease in mRNA levels of SREBP1-C, FAS, SCD1 and ACC1 involved in de novo lipogenesis and a reduction of levels of GPAT1, DGAT1 and DGAT2 related to triglyceride synthesis. Dietary salecan also increased the mRNA levels of PPARα and CYP7A1, which are related to fatty acid oxidation and cholesterol decomposition, respectively. In the 1 H nuclear magnetic resonance metabolomic analysis, both the serum and liver metabolite profiles differed among the control groups, and the metabolic profiles of the salecan groups were shifted toward that of the low-fat-diet group. Metabolites analysis showed that salecan significantly increased hepatic glutathione and betaine levels which are related to regulation of cellular reactive oxygen species. These data demonstrate that dietary salecan not only disturbed fat digestion and absorption but also influenced lipid accumulation and metabolism in diet-induced obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Mandatory trans fat labeling regulations and nationwide product reformulations to reduce trans fatty acid content in foods contributed to lowered concentrations of trans fat in Canadian women's breast milk samples collected in 2009-2011.

    Science.gov (United States)

    Ratnayake, Wm Nimal; Swist, Eleonora; Zoka, Rana; Gagnon, Claude; Lillycrop, William; Pantazapoulos, Peter

    2014-10-01

    Recent efforts in Canada to reduce industrial trans fatty acids (TFAs) in foods include mandated inclusion of TFA content on food labels and recommendations by Health Canada that encourage the food industry to voluntarily limit TFA content in all vegetable oils and soft margarines and in all other prepackaged foods to labeling regulations introduced in 2003 and recommendations by Health Canada in 2007 instructing the food manufacturers and restaurants to limit TFAs in foods have resulted in significant reductions in TFAs in the diets of Canadian breastfeeding mothers and their breast milk. © 2014 American Society for Nutrition.

  3. Adipocyte differentiation-related protein promotes lipid accumulation in goat mammary epithelial cells.

    Science.gov (United States)

    Shi, H B; Yu, K; Luo, J; Li, J; Tian, H B; Zhu, J J; Sun, Y T; Yao, D W; Xu, H F; Shi, H P; Loor, J J

    2015-10-01

    Milk fat originates from the secretion of cytosolic lipid droplets (CLD) synthesized within mammary epithelial cells. Adipocyte differentiation-related protein (ADRP; gene symbol PLIN2) is a CLD-binding protein that is crucial for synthesis of mature CLD. Our hypothesis was that ADRP regulates CLD production and metabolism in goat mammary epithelial cells (GMEC) and thus plays a role in determining milk fat content. To understand the role of ADRP in ruminant milk fat metabolism, ADRP (PLIN2) was overexpressed or knocked down in GMEC using an adenovirus system. Immunocytochemical staining revealed that ADRP localized to the surface of CLD. Supplementation with oleic acid (OA) enhanced its colocalization with CLD surface and enhanced lipid accumulation. Overexpression of ADRP increased lipid accumulation and the concentration of triacylglycerol in GMEC. In contrast, morphological examination revealed that knockdown of ADRP decreased lipid accumulation even when OA was supplemented. This response was confirmed by the reduction in mass of cellular TG when ADRP was knocked down. The fact that knockdown of ADRP did not completely eliminate lipid accumulation at a morphological level in GMEC without OA suggests that some other compensatory factors may also aid in the process of CLD formation. The ADRP reversed the decrease of CLD accumulation induced by adipose triglyceride lipase. This is highly suggestive of ADRP promoting triacylglycerol stability within CLD by preventing access to adipose triglyceride lipase. Collectively, these data provide direct in vitro evidence that ADRP plays a key role in CLD formation and stability in GMEC. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Healthy fats for healthy nutrition. An educational approach in the workplace to regulate food choices and improve prevention of non-communicable diseases.

    Science.gov (United States)

    Volpe, Roberto; Stefano, Predieri; Massimiliano, Magli; Francesca, Martelli; Gianluca, Sotis; Federica, Rossi

    2015-12-01

    An educational activity, aimed at highlighting the benefits of Mediterranean Diet, compared to less healthy eating patterns, can encourage the adoption and maintenance of a mindful approach to food choice. This is especially important when a progressive shift towards a non-Mediterranean dietary pattern can be observed, even in Mediterranean countries. To test a protocol aimed at increasing knowledge and motivation to embrace healthy eating habits and, engendering conscientious food choices, improve the prevention of non-communicable diseases. Employees were involved in educational activities focusing on a healthy Mediterranean diet and on the role played by extra-virgin olive oil, one of its key components. Food questionnaires were completed both before and after the educational and information activities, in order to assess changes in personal knowledge of and attitudes towards fat consumption. Answers on dietary guidelines and fat properties were more accurate after the seminars. The results showed increased understanding of the properties of extra-virgin olive oil versus seed oil and a stronger tendency towards healthy food choices. Implementing preventive information and training strategies and tools in the workplace, can motivate a more mindful approach to food choice with the long-term goal of contribute to reducing non-communicable diseases.

  5. Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy.

    Science.gov (United States)

    Gumucio, Jonathan P; Davis, Max E; Bradley, Joshua R; Stafford, Patrick L; Schiffman, Corey J; Lynch, Evan B; Claflin, Dennis R; Bedi, Asheesh; Mendias, Christopher L

    2012-12-01

    Full-thickness tears to the rotator cuff can cause severe pain and disability. Untreated tears progress in size and are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of rotator cuff tears, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential. Using a rat model of rotator cuff injury, we measured the force generating capacity of individual muscle fibers and determined changes in muscle fiber type distribution that develop after a full thickness rotator cuff tear. We also measured the expression of mRNA and miRNA transcripts involved in muscle atrophy, lipid accumulation, and matrix synthesis. We hypothesized that a decrease in specific force of rotator cuff muscle fibers, an accumulation of type IIb fibers, and an upregulation in fibrogenic, adipogenic, and inflammatory gene expression occur in torn rotator cuff muscles. Thirty days following rotator cuff tear, we observed a reduction in muscle fiber force production, an induction of fibrogenic, adipogenic, and autophagocytic mRNA and miRNA molecules, and a dramatic accumulation of macrophages in areas of fat accumulation. Copyright © 2012 Orthopaedic Research Society.

  6. An oilseed rape WRKY-type transcription factor regulates ROS accumulation and leaf senescence in Nicotiana benthamiana and Arabidopsis through modulating transcription of RbohD and RbohF.

    Science.gov (United States)

    Yang, Liu; Ye, Chaofei; Zhao, Yuting; Cheng, Xiaolin; Wang, Yiqiao; Jiang, Yuan-Qing; Yang, Bo

    2018-06-01

    Overexpression of BnaWGR1 causes ROS accumulation and promotes leaf senescence. BnaWGR1 binds to promoters of RbohD and RbohF and regulates their expression. Manipulation of leaf senescence process affects agricultural traits of crop plants, including biomass, seed yield and stress resistance. Since delayed leaf senescence usually enhances tolerance to multiple stresses, we analyzed the function of specific MAPK-WRKY cascades in abiotic and biotic stress tolerance as well as leaf senescence in oilseed rape (Brassica napus L.), one of the important oil crops. In the present study, we showed that expression of one WRKY gene from oilseed rape, BnaWGR1, induced an accumulation of reactive oxygen species (ROS), cell death and precocious leaf senescence both in Nicotiana benthamiana and transgenic Arabidopsis (Arabidopsis thaliana). BnaWGR1 regulates the transcription of two genes encoding key enzymes implicated in production of ROS, that is, respiratory burst oxidase homolog (Rboh) D and RbohF. A dual-luciferase reporter assay confirmed the transcriptional regulation of RbohD and RbohF by BnaWGR1. In vitro electrophoresis mobility shift assay (EMSA) showed that BnaWGR1 could bind to W-box cis-elements within promoters of RbohD and RbohF. Moreover, RbohD and RbohF were significantly upregulated in transgenic Arabidopsis overexpressing BnaWGR1. In summary, these results suggest that BnaWGR1 could positively regulate leaf senescence through regulating the expression of RbohD and RbohF genes.

  7. Reducing Abdominal Fat Deposition in Broiler Through Feeding Management

    OpenAIRE

    Cecep Hidayat

    2015-01-01

    Abdominal fat in broiler carcass is considered as a waste and its existence reduces the carcass quality. Abdominal fat deposition is affected by several factors such as genetic, nutrition, feed, sex, age and environment. Reducing abdominal fat deposition can be carried out by regulating the nutrient intake to ensure that no excessive nutrient was consumed. Nutrition effects to reduce abdominal fat deposition are associated with nutrient concentration of ration and quantity of daily feed intak...

  8. Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice.

    NARCIS (Netherlands)

    Escande, C.; Chini, C.C.; Nin, V.; Dykhouse, K.M.; Novak, C.M.; Levine, J.; Deursen, J.M.A. van; Gores, G.J.; Chen, J.; Lou, Z.; Chini, E.N.

    2010-01-01

    The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As SIRT1 activity in vitro was recently found to be negatively regulated by interaction with the deleted in

  9. The dynamics of fat, protein and sugar metabolism during walnut ...

    African Journals Online (AJOL)

    The result shows that the developmental process of walnut fruit could be divided into four stages: Slow growth {within 30 days after florescence, (DAF)}, fast growth (30 to 60 DAF), fat accumulation (60 to 100 DAF) and fruit maturity (100 to 140 DAF). Fat content in walnut fruit increased continuously and the maximum ...

  10. Loss of PTB or negative regulation of Notch mRNA reveals distinct zones of Notch and actin protein accumulation in Drosophila embryo.

    Directory of Open Access Journals (Sweden)

    Cedric S Wesley

    Full Text Available Polypyrimidine Tract Binding (PTB protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1 the Notch mRNA is a potential target of PTB, (2 PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3 the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions.

  11. Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

    Science.gov (United States)

    Wesley, Cedric S.; Guo, Heng; Chaudhry, Kanita A.; Thali, Markus J.; Yin, Jerry C.; Clason, Todd; Wesley, Umadevi V.

    2011-01-01

    Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions. PMID:21750738

  12. The subcutaneous abdominal fat and not the intraabdominal fat compartment is associated with anovulation in women with obesity and infertility.

    Science.gov (United States)

    Kuchenbecker, Walter K H; Groen, Henk; Zijlstra, Tineke M; Bolster, Johanna H T; Slart, Riemer H J; van der Jagt, Erik J; Kobold, Anneke C Muller; Wolffenbuttel, Bruce H R; Land, Jolande A; Hoek, Annemieke

    2010-05-01

    Abdominal fat contributes to anovulation. We compared body fat distribution measurements and their contribution to anovulation in obese ovulatory and anovulatory infertile women. Seventeen ovulatory and 40 anovulatory women (age, 30 +/- 4 yr; body mass index, 37.7 +/- 6.1 kg/m(2)) participated. Body fat distribution was measured by anthropometrics, dual-energy x-ray absorptiometry, and single-sliced abdominal computed tomography scan. Multiple logistic regression analysis was applied to determine which fat compartments significantly contributed to anovulation. Anovulatory women had a higher waist circumference (113 +/- 11 vs. 104 +/- 9 cm; P fat (23.0 +/- 5.3 vs. 19.1 +/- 4.2 kg; P abdominal fat (4.4 +/- 1.3 kg vs. 3.5 +/- 0.9 kg; P fat on single-sliced abdominal computed tomography scan was not significantly different between the two groups (203 +/- 56 vs. 195 +/- 71 cm(3); P = 0.65), but anovulatory women had significantly more sc abdominal fat (SAF) (992 +/- 198 vs. 864 +/- 146 cm(3); P fat, abdominal fat, and SAF were associated with anovulation. Abdominal fat is increased in anovulatory women due to a significant increase in SAF and not in intraabdominal fat. SAF and especially abdominal and trunk fat accumulation are associated with anovulation.

  13. Chronic Exposure to Rhodobacter Sphaeroides Extract Lycogen™ Prevents UVA-Induced Malondialdehyde Accumulation and Procollagen I Down-Regulation in Human Dermal Fibroblasts

    Science.gov (United States)

    Yang, Tsai-Hsiu; Lai, Ying-Hsiu; Lin, Tsuey-Pin; Liu, Wen-Sheng; Kuan, Li-Chun; Liu, Chia-Chyuan

    2014-01-01

    UVA contributes to the pathogenesis of skin aging by downregulation of procollagen I content and induction of matrix metalloproteinase (MMP)-associated responses. Application of antioxidants such as lycopene has been demonstrated as a convenient way to achieve protection against skin aging. Lycogen™, derived from the extracts of Rhodobacter sphaeroides, exerts several biological effects similar to that of lycopene whereas most of its anti-aging efficacy remains uncertain. In this study, we attempted to examine whether Lycogen™ could suppress malondialdehyde (MDA) accumulation and restore downregulated procollagen I expression induced by UVA exposure. In human dermal fibroblasts Hs68 cells, UVA repressed cell viability and decreased procollagen I protein content accompanied with the induction of MMP-1 and MDA accumulation. Remarkably, incubation with 50 μM Lycogen™ for 24 h ameliorated UVA-induced cell death and restored UVA-induced downregulation of procollagen in a dose-related manner. Lycogen™ treatment also prevented the UVA-induced MMP-1 upregulation and intracellular MDA generation in Hs68 cells. Activation of NFκB levels, one of the downstream events induced by UVA irradiation and MMP-1 induction, were also prevented by Lycogen™ administration. Taken together, our findings demonstrate that Lycogen™ may be an alternative agent that prevents UVA-induced skin aging and could be used in cosmetic and pharmaceutical applications. PMID:24463291

  14. High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

    Science.gov (United States)

    Gao, Mingming; Ma, Yongjie; Liu, Dexi

    2015-01-01

    High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

  15. High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

    Directory of Open Access Journals (Sweden)

    Mingming Gao

    Full Text Available High-fat diet (HFD has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

  16. Relationship between waist circumference, visceral fat and ...

    African Journals Online (AJOL)

    Results: The prevalence was higher in women for enlarged waist circumference according to the pathological IDF or NCEP / ATP III threshold (p < 0.0001) contrasting with lower rates for pathological accumulation of visceral fat in men (p = 0.0001). The highest values for sensitivity and specificity were obtained for a ...

  17. Dietary fat composition influences tissue lipid profile and gene expression in Fischer-344 rats.

    Science.gov (United States)

    Zhou, Albert L; Hintze, Korry J; Jimenez-Flores, Rafael; Ward, Robert E

    2012-12-01

    The AIN-76A diet causes fatty liver in rodents when fed for long periods of time. The aim of this study was to utilize fatty acid analysis and transcriptomics to investigate the effects of different fat sources in the AIN-76A diet on tissue lipid profiles and gene expression in male, weanling Fischer-344 rats. Animals were fed isocaloric diets that differed only in the fat source: (1) corn oil (CO) (2) anhydrous milk fat (AMF), and (3) AMF supplemented with 10% phospholipids from the milk fat globule membrane (AMF-MFGM). There were no differences in food intake, body weight, growth rate, or body fat composition among the groups, and the fatty acid compositions of red blood cells (RBC), plasma, muscle, and visceral adipose tissues reflected the dietary fat sources. Modifying the fat source resulted in 293 genes differentially regulated in skeletal muscle, 1,124 in adipose, and 831 in liver as determined by analysis of variance (ANOVA). Although tissue fatty acid profiles mostly reflected the diet, there were several quantitative differences in lipid classes in the liver and plasma. The AMF diet resulted in the highest level of hepatic triacylglycerols, but the lowest level in plasma. The CO diet resulted in significant accumulation of hepatic unesterified fatty acids and decreased DGAT expression and activity, a potential trigger for steatohepatitis. These results indicate that the fatty acid composition and presence of polar lipids in the AIN-76A diets have significant effects on lipid partitioning, gene expression, and potentially the development of liver pathology.

  18. Esculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway.

    Science.gov (United States)

    Pandey, Anuradha; Raj, Priyank; Goru, Santosh Kumar; Kadakol, Almesh; Malek, Vajir; Sharma, Nisha; Gaikwad, Anil Bhanudas

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder is associated with oxidative stress, inflammation and fibrotic cascades. In this study, we aimed to examine the effects of Esculetin, a well-known anti-oxidant on TGF-β1 mediated liver fibrosis and FoxO1 activity. A non-genetic murine model for NAFLD was developed by chronic high fat diet (HFD) (58% calories from fats) feeding in Wistar rats. The plasma biochemical parameters, liver function tests, oxidative stress, and histopathological alterations were assessed. The alterations in extracellular matrix (ECM) deposition and FoxO1 activity were assessed by immunohistochemistry. The aberrations in plasma parameters, liver functioning, morphometric and microscopic changes in liver structure of HFD fed rats were significantly improved by treatment with Esculetin. Liver fibrosis, identified in the form of collagen deposition and expression of fibrotic proteins like TGF-β1 and fibronectin was also markedly controlled by Esculetin. The expression of phospho-FoxO1 was found to be reduced in HFD fed rats' liver, showing an increase in activation of FoxO1 under insulin resistant and hyperglycemic states. Esculetin treatment could improve phospho-FoxO1 expression, thus showing its ability to act on Akt/PI3K/FoxO1 pathway. As per the previous studies, a potential therapy for NAFLD may be the one with multi-faceted actions on insulin resistance, oxidative stress, inflammation and fibrosis. This study demonstrates the efficiency of Esculetin in improving liver fibrosis in HFD induced NAFLD. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Seminal Fluid Regulates Accumulation of FOXP3(+) Regulatory T Cells in the Preimplantation Mouse Uterus Through Expanding the FOXP3(+) Cell Pool and CCL19-Mediated Recruitment

    NARCIS (Netherlands)

    Guerin, Leigh R.; Moldenhauer, Lachlan M.; Prins, Jelmer R.; Bromfield, John J.; Hayball, John D.; Robertson, Sarah A.

    Regulatory T (Treg) cells facilitate maternal immune tolerance of the semiallogeneic conceptus in early pregnancy, but the origin and regulation of these cells at embryo implantation is unclear. During the preimplantation period, factors in the seminal fluid delivered at coitus cause expansion of a

  20. The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet

    Directory of Open Access Journals (Sweden)

    Min Hee Kim

    2017-04-01

    Conclusion: These results suggest the possibility that GBx can ameliorate blood flow by decreasing intima-media thickness via the regulation of blood coagulation factors related to lipid metabolites in rats fed a HFD.

  1. Improvement of the safety regulations in the management of radioactive waste accumulated in the liquid radioactive waste water basins of the PO 'Majak' (Ozersk), the Siberian Chemical Plant (Seversk) and the Mining-Chemical Plant (Zheleznogorsk)

    International Nuclear Information System (INIS)

    Vishnevski, Y.G.; Kislov, A.I.; Irushkin, V.M.

    2002-01-01

    One of the most important problems of radiation safety in Russia is the decommissioning of the liquid radioactive waste water basins of the PO 'Majak' (Ozersk), Siberian Chemical Plant (Seversk) and Mining-Chemical Plant (Zheleznogorsk). The liquid radioactive waste water basins were constructed in 1950-1960 for the collection and storage of liquid waste from the radiochemical plants. The potential hazards of the liquid in the radioactive waste water basins are: migration of radionuclides into the soil of the liquid radioactive waste water basin floors; wind-induced carry-over of radionuclides from the liquid radioactive waste water basins; hazards (radiation included) to the environment and population arising in case physical barriers and hydraulic structures are damaged; and criticality hazards. The classification of the liquid radioactive waste water basins were developed based on the collection and analyzes of the information on liquid radioactive waste water basin characteristics and the method of multicriterion expert assessment of potential hazards. Three main directions for the improvement of safety regulation in the management of radioactive waste accumulated in the liquid radioactive waste water basins were defined: 1. Common directions for the improvement of safety regulation in the area of rehabilitation of the territories contaminated with radioactive substances. 2. Common directions for the improvement of safety regulation in the area of rehabilitation of the territories, such as the liquid radioactive waste water basins. 3. Special directions for the regulatory activities in the area of operation and decommissioning of the liquid radioactive waste water basins of the PO 'Majak' (Ozersk), Siberian Chemical Plant (Seversk) and Mining-Chemical Plant (Zheleznogorsk). As a result, concrete recommendations on safety regulation for the management of radioactive waste accumulated in the water basins were developed. (author)

  2. Anti-Obesity Effect of 6,8-Diprenylgenistein, an Isoflavonoid of Cudrania tricuspidata Fruits in High-Fat Diet-Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Yang Hee Jo

    2015-12-01

    Full Text Available Obesity, which is characterized by excessive fat accumulation, is associated with several pathological disorders, including metabolic diseases. In this study, the anti-obesity effect of 6,8-diprenylgenistein (DPG, a major isoflavonoid of Cudrania tricuspidata fruits was investigated using high fat-diet (HFD-induced obese mice at the doses of 10 and 30 mg/kg for six week. The body weight of the DPG-treated groups was significantly lower compared to the HFD-treated group. In addition, fat accumulation in epididymal adipose tissue and liver was dramatically decreased in the HFD + DPG groups. The food efficiency ratios of the HFD + DPG groups were also lower compared to the HFD group with the same food intake. Metabolic parameters that had increased in the HFD group were decreased in the HFD + DPG groups. Further studies demonstrate that DPG efficiently reduces lipogenic genes by regulation of transcription factors, such as peroxisome proliferator-activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα, and hormones, such as leptin and adiponection. DPG also regulates acetyl-CoA carboxylase (ACC and hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR by AMP-activated protein kinase (AMPK activation. Taken together, DPG is beneficial for the regulation of obesity, especially resulting from high fat intake.

  3. Intraventricular administration of Tenebrio molitor larvae extract regulates food intake and body weight in mice with high-fat diet-induced obesity.

    Science.gov (United States)

    Seo, Minchul; Kim, Jongwan; Moon, Seong-Su; Hwang, Jae-Sam; Kim, Mi-Ae

    2017-08-01

    We recently reported the in vitro and in vivo antiobesity effects of Tenebrio molitor larvae, a traditional food in many countries, but it remains unknown how the larvae affect appetite regulation in mice with diet-induced obesity. We hypothesized that the extract of T molitor larvae mediates appetite by regulating neuropeptide expression. We investigated T molitor larvae extract's (TME's) effects on anorexigenesis and endoplasmic reticulum (ER) stress-induced orexigenic neuropeptide expression in the hypothalami of obese mice. Intracerebroventricular TME administration suppressed feeding by down-regulating the expression of the orexigenic neuropeptides neuropeptide Y and agouti-related protein. T molitor larvae extract significantly reduced the expression of ER stress response genes. These results suggest that TME and its bioactive components are potential therapeutics for obesity and ER stress-driven disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. CPB1 of Aedes aegypti Interacts with DENV2 E Protein and Regulates Intracellular Viral Accumulation and Release from Midgut Cells

    Directory of Open Access Journals (Sweden)

    Hong-Wai Tham

    2014-12-01

    Full Text Available Aedes aegypti is a principal vector responsible for the transmission of dengue viruses (DENV. To date, vector control remains the key option for dengue disease management. To develop new vector control strategies, a more comprehensive understanding of the biological interactions between DENV and Ae. aegypti is required. In this study, a cDNA library derived from the midgut of female adult Ae. aegypti was used in yeast two-hybrid (Y2H screenings against DENV2 envelope (E protein. Among the many interacting proteins identified, carboxypeptidase B1 (CPB1 was selected, and its biological interaction with E protein in Ae. aegypti primary midgut cells was further validated. Our double immunofluorescent assay showed that CPB1-E interaction occurred in the endoplasmic reticulum (ER of the Ae. aegypti primary midgut cells. Overexpression of CPB1 in mosquito cells resulted in intracellular DENV2 genomic RNA or virus particle accumulation, with a lower amount of virus release. Therefore, we postulated that in Ae. aegypti midgut cells, CPB1 binds to the E protein deposited on the ER intraluminal membranes and inhibits DENV2 RNA encapsulation, thus inhibiting budding from the ER, and may interfere with immature virus transportation to the trans-Golgi network.

  5. A new mechanism for the regulation of stomatal aperture size in intact leaves: accumulation of mesophyll-derived sucrose in the guard-cell wall of Vicia faba

    International Nuclear Information System (INIS)

    Lu, P.; Outlaw, W.H. Jr.; Smith, B.G.; Freed, G.A.

    1997-01-01

    At various times after pulse-labeling broad bean (Vicia faba L.) leaflets with 14CO2, whole-leaf pieces and rinsed epidermal peels were harvested and subsequently processed for histochemical analysis. Cells dissected from whole leaf retained apoplastic contents, whereas those from rinsed peels contained only symplastic contents. Sucrose (Suc)-specific radioactivity peaked (111 GBq mol-1) in palisade cells at 20 min. In contrast, the 14C content and Suc-specific radioactivity were very low in guard cells for 20 min, implying little CO2 incorporation; both then peaked at 40 min. The guard-cell apoplast had a high maximum Suc-specific radioactivity (204 GBq mol-1) and a high Suc influx rate (0.05 pmol stoma-1 min-1). These and other comparisons implied the presence of (a) multiple Suc pools in mesophyll cells, (b) a localized mesophyll-apoplast region that exchanges with phloem and stomata, and (c) mesophyll-derived Suc in guard-cell walls sufficient to diminish stomatal opening by approximately 3 micrometers. Factors expected to enhance Suc accumulation in guard-cell walls are (a) high transpiration rate, which closes stomata, and (b) high apoplastic Suc concentration, which is elevated when mesophyll Suc efflux exceeds translocation. Therefore, multiple physiological factors are integrated in the attenuation of stomatal aperture size by this previously unrecognized mechanism

  6. Fecal Fat: The Test

    Science.gov (United States)

    ... and, in severe cases, symptoms of malnutrition and vitamin deficiency. If the condition prevents the digestion and/or absorption of fats from the diet, then excess fat is present in the stool and the ...

  7. Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux

    Directory of Open Access Journals (Sweden)

    Xiao Xie

    2017-05-01

    Full Text Available Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR or dietary polyphenols such as green tea polyphenols (GTPs can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD, DR, high-fat diet (HFD, and three diets plus 200 mg/kg(bw/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-β-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA-treated human proximal tubular epithelial cells (HK-2, which was ameliorated by epigallocatechin-3-gallate (EGCG. Furthermore, GTPs (or EGCG elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression.

  8. A biological timer in the fat body comprising Blimp-1, βFtz-f1 and Shade regulates pupation timing in Drosophila melanogaster.

    Science.gov (United States)

    Akagi, Kazutaka; Sarhan, Moustafa; Sultan, Abdel-Rahman S; Nishida, Haruka; Koie, Azusa; Nakayama, Takumi; Ueda, Hitoshi

    2016-07-01

    During the development of multicellular organisms, many events occur with precise timing. In Drosophila melanogaster, pupation occurs about 12 h after puparium formation and its timing is believed to be determined by the release of a steroid hormone, ecdysone (E), from the prothoracic gland. Here, we demonstrate that the ecdysone-20-monooxygenase Shade determines pupation timing by converting E to 20-hydroxyecdysone (20E) in the fat body, which is the organ that senses nutritional status. The timing of shade expression is determined by its transcriptional activator βFtz-f1. The βftz-f1 gene is activated after a decline in the expression of its transcriptional repressor Blimp-1, which is temporally expressed around puparium formation in response to a high titer of 20E. The expression level and stability of Blimp-1 is critical for the precise timing of pupation. Thus, we propose that Blimp-1 molecules function like sand in an hourglass in this precise developmental timer system. Furthermore, our data suggest that a biological advantage results from both the use of a transcriptional repressor for time determination and the association of developmental timing with nutritional status of the organism. © 2016. Published by The Company of Biologists Ltd.

  9. Detrimental and protective fat: body fat distribution and its relation to metabolic disease.

    Science.gov (United States)

    Booth, Andrea; Magnuson, Aaron; Foster, Michelle

    2014-01-01

    Obesity is linked to numerous comorbidities that include, but are not limited to, glucose intolerance, insulin resistance, dyslipidemia, and cardiovascular disease. Current evidence suggests, however, obesity itself is not an exclusive predictor of metabolic dysregulation but rather adipose tissue distribution. Obesity-related adverse health consequences occur predominately in individuals with upper body fat accumulation, the detrimental distribution, commonly associated with visceral obesity. Increased lower body subcutaneous adipose tissue, however, is associated with a reduced risk of obesity-induced metabolic dysregulation and even enhanced insulin sensitivity, thus, storage in this region is considered protective. The proposed mechanisms that causally relate the differential outcomes of adipose tissue distribution are often attributed to location and/or adipocyte regulation. Visceral adipose tissue effluent to the portal vein drains into the liver where hepatocytes are directly exposed to its metabolites and secretory products, whereas the subcutaneous adipose tissue drains systemically. Adipose depots are also inherently different in numerous ways such as adipokine release, immunity response and regulation, lipid turnover, rate of cell growth and death, and response to stress and sex hormones. Proximal extrinsic factors also play a role in the differential drive between adipose tissue depots. This review focuses on the deleterious mechanisms postulated to drive the differential metabolic response between central and lower body adipose tissue distribution.

  10. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance

    DEFF Research Database (Denmark)

    Madsen, Lise; Guerre-Millo, Michéle; Flindt, Esben N

    2002-01-01

    Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration...... completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA...... that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity....

  11. Comprehensive analyses of DNA methylation profile, regulation on flowering, and seed mineral accumulation in Arabidopsis thaliana in response to zinc deficiency

    OpenAIRE

    Chen Xiaochao

    2016-01-01

    Zinc (Zn) is an essential micronutrient for plant growth and development, which plays important roles in DNA binding, metabolic, catalytic and transcriptional regulator activities. However, Zn deficiency is a worldwide problem due to its limited bioavailability in soils in many agricultural areas, often as a result of high CaCO3 content and high pH. In addition, phytic acid is able to strongly chelate cations, such as Zn2+, Fe2+, Ca2+ and Mg2+ to form the phytate salts. Phytate cannot be dige...

  12. Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer

    International Nuclear Information System (INIS)

    Chang, J.-L.; Chen, T.-H.; Wang, C.-F.; Chiang, Y.-H.; Huang, Y.-L.; Wong, F.-H.; Chou, C.-K.; Chen, C.-M.

    2006-01-01

    Chromosomal passenger proteins including Aurora B, Survivin, and Borealin/Dasra B, also called CDCA8/FLJ10468, are known to play crucial roles during mitosis and cell division. Inappropriate chromosomal segregation and cell division may cause auneuploidy leading to cancer. However, it is still unclear how the expression of chromosomal passenger proteins may be linked to cancer. In this study, we demonstrated that Borealin is a cell cycle-regulated gene and is upregulated at G2-M phases of the cell cycle. We showed that Borealin interacts with Survivin but not with Aurora B. The interaction domain of Survivin in Borealin was mapped to the N-terminal 92 amino-acid residues of Borealin. To examine the linkage between expression of Borealin and cancer, we performed immunohistochemistry analysis using anti-Borealin specific antibody on the paraffin-embedded gastric cancer tissues. Our results showed that Borealin expression is significantly correlated with Survivin (P = 0.003) and Ki67 (P = 0.007) in gastric cancer. Interestingly, an increased nuclear Borealin level reveals borderline association with a poor survival rate (P = 0.047). Taken together, our results demonstrated that Borealin is a cell cycle-regulated chromosomal passenger protein and its aberrant expression is linked to a poor prognosis for gastric cancer

  13. The role of glucose, insulin and NEFA in regulating tissue triglyceride accumulation: Substrate cooperation in adipose tissue versus substrate competition in skeletal muscle.

    Science.gov (United States)

    Guzzardi, M A; Hodson, L; Guiducci, L; La Rosa, F; Salvadori, P A; Burchielli, S; Iozzo, P

    2017-11-01

    Metabolic factors initiating adipose tissue expansion and ectopic triglyceride accumulation are not completely understood. We aimed to investigate the independent role of circulating glucose, NEFA and insulin on glucose and NEFA uptake, and lipogenesis in skeletal muscle and subcutaneous adipose tissue (SCAT). Twenty-two pigs were stratified according to four protocols: 1) and 2) low NEFA + high insulin ± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia-euglycaemia), 3) high NEFA + low insulin (fasting), 4) low NEFA + low insulin (nicotinic acid). Positron emission tomography with [ 18 F]fluoro-2-deoxyglucose and [ 11 C]acetate, was combined with [ 14 C]acetate and [U- 13 C]palmitate enrichment techniques to assess glucose and lipid metabolism. Hyperinsulinaemia increased glucose extraction, whilst hyperglycaemia enhanced glucose uptake in skeletal muscle and SCAT. In SCAT, during hyperglycaemia, elevated glucose uptake was accompanied by greater [U- 13 C]palmitate-TG enrichment compared to the other groups, and by a 39% increase in de novo lipogenesis (DNL) compared to baseline, consistent with a 70% increment in plasma lipogenic index. Conversely, in skeletal muscle, [U- 13 C]palmitate-TG enrichment was higher after prolonged fasting. Our data show the necessary role of hyperglycaemia-hyperinsulinaemia vs euglycaemia-hyperinsulinaemia in promoting expansion of TG stores in SCAT, by the consensual elevation in plasma NEFA and glucose uptake and DNL. In contrast, skeletal muscle NEFA uptake for TG synthesis is primarily driven by circulating NEFA levels. These results suggest that a) prolonged fasting or dietary regimens enhancing lipolysis might promote muscle steatosis, and b) the control of glucose levels, in association with adequate energy balance, might contribute to weight loss. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and

  14. Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism in apo E(-/-) mice.

    Science.gov (United States)

    Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Park, Yong-Bok; Lee, Ki-Teak; Park, Taesun; Choi, Myung-Sook

    2009-07-01

    The objective of this study was to explicate the effects of feeding low trans structured fat from flaxseed oil (LF) on plasma and hepatic lipid metabolism involved in apo E(-/-) mice. The animals were fed a commercial shortening (CS), commercial low trans fat (CL) and LF diet based on AIN-76 diet (10% fat) for 12 weeks. LF supplementation exerted a significant suppression in hepatic lipid accumulation with the concomitant decrease in liver weight. The LF significantly lowered plasma total cholesterol and free fatty acid whereas it significantly increased HDL-C concentration and the HDL-C/total-C ratio compared to the CS group. Reduction of hepatic lipid levels in the LF group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis, and cholesterol regulating enzyme activity compared to the CS and CL groups. Accordingly, low trans structured fat from flaxseed oil is highly effective for improving hyperlipidemia and hepatic lipid accumulation in apo E(-/-) mice.

  15. Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.

    Science.gov (United States)

    Yuan, Fahu; Wang, Hualin; Tian, Yu; Li, Qi; He, Lei; Li, Na; Liu, Zhiguo

    2016-02-01

    Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.

  16. Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25

    DEFF Research Database (Denmark)

    Mullaney, Brendan C; Blind, Raymond D; Lemieux, George A

    2010-01-01

    Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules, and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3...... mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3-derived long-chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine...... program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans....

  17. Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

    Science.gov (United States)

    Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Abdullah, Maizaton Atmadini; Basri, Hamidon

    2017-11-01

    Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue. Copyright © 2017 Elsevier

  18. Reducing Abdominal Fat Deposition in Broiler Through Feeding Management

    Directory of Open Access Journals (Sweden)

    Cecep Hidayat

    2015-09-01

    Full Text Available Abdominal fat in broiler carcass is considered as a waste and its existence reduces the carcass quality. Abdominal fat deposition is affected by several factors such as genetic, nutrition, feed, sex, age and environment. Reducing abdominal fat deposition can be carried out by regulating the nutrient intake to ensure that no excessive nutrient was consumed. Nutrition effects to reduce abdominal fat deposition are associated with nutrient concentration of ration and quantity of daily feed intake. Daily nutrient intake can be limited, especially through restricted feeding. It is concluded that an appropriate feeding management can reduce abdominal fat deposition in broiler.

  19. Fat utilization during exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Watt, Peter W.; Richter, Erik

    2001-01-01

    1. This study was carried out to test the hypothesis that the greater fat oxidation observed during exercise after adaptation to a high-fat diet is due to an increased uptake of fat originating from the bloodstream. 2. Of 13 male untrained subjects, seven consumed a fat-rich diet (62 % fat, 21...... % carbohydrate) and six consumed a carbohydrate-rich diet (20 % fat, 65 % carbohydrate). After 7 weeks of training and diet, 60 min of bicycle exercise was performed at 68 +/- 1 % of maximum oxygen uptake. During exercise [1-(13)C]palmitate was infused, arterial and venous femoral blood samples were collected......, and blood flow was determined by the thermodilution technique. Muscle biopsy samples were taken from the vastus lateralis muscle before and after exercise. 3. During exercise, the respiratory exchange ratio was significantly lower in subjects consuming the fat-rich diet (0.86 +/- 0.01, mean +/- S.E.M.) than...

  20. Drought and exogenous abscisic acid alter hydrogen peroxide accumulation and differentially regulate the expression of two maize RD22-like genes.

    Science.gov (United States)

    Phillips, Kyle; Ludidi, Ndiko

    2017-08-18

    Increased biosynthesis of abscisic acid (ABA) occurs in plants in response to water deficit, which is mediated by changes in the levels of reactive oxygen species such as H 2 O 2 . Water deficit and ABA induce expression of some RD22-like proteins. This study aimed to evaluate the effect of water deficit and exogenous ABA (50 µM ABA applied every 24 hours for a total of 72 hours) on H 2 O 2 content in Zea mays (maize) and to characterise genes encoding two putative maize RD22-like proteins (designated ZmRD22A and ZmRD22B). The expression profiles of the two putative maize RD22-like genes in response to water deficit and treatment with ABA were examined in leaves. In silico analyses showed that the maize RD22-like proteins share domain organisation with previously characterized RD22-like proteins. Both water deficit and exogenous ABA resulted in increased H 2 O 2 content in leaves but the increase was more pronounced in response to water deficit than to exogenous ABA. Lignin content was not affected by exogenous ABA, whereas it was decreased by water deficit. Expression of both RD22-like genes was up-regulated by drought but the ZmRD22A gene was not influenced by exogenous ABA, whereas ZmRD22B was highly responsive to exogenous ABA.

  1. Effect of body fat distribution on the transcription response to dietary fat interventions

    NARCIS (Netherlands)

    Radonjic, M.; Erk, M.J. van; Pasman, W.J.; Wortelboer, H.M.; Hendriks, H.F.J.; Ommen, B. van

    2009-01-01

    Combination of decreased energy expenditure and increased food intake results in fat accumulation either in the abdominal site (upper body obesity, UBO) or on the hips (lower body obesity, LBO). In this study, we used microarray gene expression profiling of adipose tissue biopsies to investigate the

  2. Quantification of liver fat: A comprehensive review.

    Science.gov (United States)

    Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

    2016-04-01

    Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The Resin from Protium heptaphyllum Prevents High-Fat Diet-Induced Obesity in Mice: Scientific Evidence and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Karine Maria Martins Bezerra Carvalho

    2015-01-01

    Full Text Available Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism and to have beneficial effects on metabolic disorders. The present study investigated the antiobesity properties of resin from Protium heptaphyllum (RPH and the possible mechanisms in mice fed a high-fat diet (HFD for 15 weeks. Mice treated with RPH showed decreases in body weight, net energy intake, abdominal fat accumulation, plasma glucose, amylase, lipase, triglycerides, and total cholesterol relative to their respective controls, which were RPH unfed. Additionally, RPH treatment, while significantly elevating the plasma level of ghrelin hormone, decreased the levels of insulin, leptin, and resistin. Besides, HFD-induced increases in plasma levels of proinflammatory mediators TNF-α, IL-6, and MCP-1 were significantly lowered by RPH. Furthermore, in vitro studies revealed that RPH could significantly inhibit the lipid accumulation in 3T3-L1 adipocytes (measured by Oil-Red O staining at concentrations up to 50 μg/mL. These findings suggest that the antiobese potential of RPH is largely due to its modulatory effects on various hormonal and enzymatic secretions related to fat and carbohydrate metabolism and to the regulation of obesity-associated inflammation.

  4. SCAPIS Pilot Study: Sitness, Fitness and Fatness - Is Sedentary Time Substitution by Physical Activity Equally Important for Everyone's Markers of Glucose Regulation?

    Science.gov (United States)

    Ekblom-Bak, Elin; Ekblom, Örjan; Bolam, Kate A; Ekblom, Björn; Bergström, Göran; Börjesson, Mats

    2016-07-01

    Although moderate-to-vigorous physical activity (MVPA) is mainly recommended for glucose control, light physical activity (LIPA) may also have the potential to induce favorable changes. We investigated sedentary time (SED) substitution with equal time in LIPA and MVPA, and the association with markers of glucose regulation and insulin sensitivity after stratification by waist circumference, fitness and fasting glucose levels. A total of 654 men and women, 50 to 64 years, from the SCAPIS pilot study were included. Daily SED, LIPA and MVPA were assessed using hip-worn accelerometers. Fasting plasma glucose, insulin and HOMA-IR were determined. Substituting 30 min of SED with LIPA was significantly associated with 3.0% lower fasting insulin values and 3.1% lower HOMA-IR values, with even lower levels when substituting SED with MVPA. Participants with lower fitness and participants with high fasting glucose levels benefited significantly more from substituting 30 min of SED with LIPA compared with participants with normal to high fitness levels and participants with normal glucose levels, respectively. LIPA, and not only MVPA, may have beneficial associations with glucose regulation. This is of great clinical and public health importance, not least because it may confer a higher compliance rate to regular PA.

  5. Arrhythmia causes lipid accumulation and reduced glucose uptake.

    Science.gov (United States)

    Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

    2015-01-01

    Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

  6. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nut rition and Allergies ) , 2013. Scientific Opinion on the substantiation of a health claim related to the c onsum ption of 2 g/day of plant stanols (as plant stanol ester s ) as part of a diet low in saturated fat and a two - fold greater, reduction in blood LDL - chol esterol concentrations compared to the consumption of a diet low in saturated fat alone pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from McNeil Nutritionals and Raisio Nutrition Ltd, submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked...... to deliver an opinion on the scientific substantiation of a health claim related to the consumption of 2 g/day of plant stanols (as plant stanol esters) as part of a diet low in saturated fat and a two-fold greater reduction in blood LDL-cholesterol concentrations compared to the consumption of a diet low...... an evaluation of the quantitative effects of diets low in saturated fat per se on blood LDL-cholesterol concentrations. Therefore, the effect of consuming 2 g/day plant stanols as part of a diet low in saturated fat relative to the effect of consuming a diet low in saturated fat alone cannot be determined...

  7. Neurobeachin, a Regulator of Synaptic Protein Targeting, Is Associated with Body Fat Mass and Feeding Behavior in Mice and Body-Mass Index in Humans

    Science.gov (United States)

    Olszewski, Pawel K.; Rozman, Jan; Jacobsson, Josefin A.; Rathkolb, Birgit; Strömberg, Siv; Hans, Wolfgang; Klockars, Anica; Alsiö, Johan; Risérus, Ulf; Becker, Lore; Hölter, Sabine M.; Elvert, Ralf; Ehrhardt, Nicole; Gailus-Durner, Valérie; Fuchs, Helmut; Fredriksson, Robert; Wolf, Eckhard; Klopstock, Thomas; Wurst, Wolfgang; Levine, Allen S.; Marcus, Claude; Hrabě de Angelis, Martin; Klingenspor, Martin; Schiöth, Helgi B.; Kilimann, Manfred W.

    2012-01-01

    Neurobeachin (Nbea) regulates neuronal membrane protein trafficking and is required for the development and functioning of central and neuromuscular synapses. In homozygous knockout (KO) mice, Nbea deficiency causes perinatal death. Here, we report that heterozygous KO mice haploinsufficient for Nbea have higher body weight due to increased adipose tissue mass. In several feeding paradigms, heterozygous KO mice consumed more food than wild-type (WT) controls, and this consumption was primarily driven by calories rather than palatability. Expression analysis of feeding-related genes in the hypothalamus and brainstem with real-time PCR showed differential expression of a subset of neuropeptide or neuropeptide receptor mRNAs between WT and Nbea+/− mice in the sated state and in response to food deprivation, but not to feeding reward. In humans, we identified two intronic NBEA single-nucleotide polymorphisms (SNPs) that are significantly associated with body-mass index (BMI) in adult and juvenile cohorts. Overall, data obtained in mice and humans suggest that variation of Nbea abundance or activity critically affects body weight, presumably by influencing the activity of feeding-related neural circuits. Our study emphasizes the importance of neural mechanisms in body weight control and points out NBEA as a potential risk gene in human obesity. PMID:22438821

  8. A Fat strange Repeller

    Institute of Scientific and Technical Information of China (English)

    申影; 何阅; 姜玉梅; 何大韧

    2004-01-01

    This article reports an observation on a fat strange repeller, which appears after a characteristic crisis observed in a kicked rotor subjected to a piecewise continuous force field. The discontinuity border in the definition range of the two-dimensional mapping, which describes the system, oscillates as the discrete time develops. At a threshold of a control parameter a fat chaotic attractor suddenly transfers to a fat transient set. The strange repeller, which appears after the crisis, is also a fat fractal. This is the reason why super-transience happens

  9. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  10. MicroRNA Regulation of Brown Adipogenesis and Thermogenic Energy Expenditure

    DEFF Research Database (Denmark)

    Shamsi, Farnaz; Zhang, Hongbin; Tseng, Yu-Hua

    2017-01-01

    Obesity, diabetes, and associated metabolic diseases have become global epidemics. Obesity results from excess accumulation of white fat, while brown and its related beige fat function to dissipate energy as heat, thus counteracting obesity and its related metabolic disorders. Understanding...... attracted a great deal of research interests in exploring their roles in physiological and pathophysiological conditions. This review focuses on the recent advances of regulating brown adipogenesis and energy metabolism by miRNAs, aiming to delineate the regulatory principles of miRNAs on this unique aspect...... of energy homeostasis....

  11. Efecto de la ración alimenticia sobre la maduración gonadal y acumulación de grasa de anchoveta peruana (Engraulis ringens Jenyns, 1842 en cautiverio Effect of feeding ration on gonad maturation and fat accumulation in Peruvian anchovy (Engraulis ringens Jenyns, 1842 in captivity

    Directory of Open Access Journals (Sweden)

    Carlos Espinoza

    2009-01-01

    in the environmental factors such as El Niño and La Niña events, which heavily affect the ecosystem and fisheries in the East Pacific. The specimens required 45 days under optimal feeding conditions (46.1 cal g-1 fish day-1 and at a temperature of 16,5°C to go from an unyoked to a vitellogenic stage. Those females fed 138.3 cal g-1 fish day-1 reached maximum vitellogenesis in 30 days. Despite the excessive amount of food, the specimens' muscle mass did not increase. However, greater body fat accumulation and larger vitellogenic ovocytes were observed, indicating augmented energy storage for the female and her offspring. The yoked oocytes from fish fed 46.1 cal g-1 fish day-1 became atretic earlier than oocytes from fish fed 138.3 cal g-1 fish day-1. Although the food supply was adequate, the females did not spawn during the experiment. In males, food availability also accelerated gonad maturation, but the release of sperm was apparently conditioned by the presence of females with ovocytes in the advanced vitellogenic stage.

  12. Dietary fat and carcinogenesis

    NARCIS (Netherlands)

    Woutersen, R.A.; Appel, M.J.; Garderen-Hoetmer, A. van; Wijnands, M.V.W.

    1999-01-01

    Epidemiologic investigations have suggested a relationship between dietary fat intake and various types of cancer incidences. Furthermore, epidemiologic studies as well as studies with animal models have demonstrated that not only the amount but also the type of fat consumed is important. At

  13. Advanced accumulator for PWR

    International Nuclear Information System (INIS)

    Ichimura, Taiki; Chikahata, Hideyuki

    1997-01-01

    Advanced accumulators have been incorporated into the APWR design in order to simplify the safety system configuration and to improve reliability. The advanced accumulators refill the reactor vessel with a large discharge flow rate in a large LOCA, then switch to a small flow rate to continue safety injection for core reflooding. The functions of the conventional accumulator and the low head safety injection pump are integrated into this advanced accumulator. Injection performance tests simulating LOCA conditions and visualization tests for new designs have been carried out. This paper describes the APWR ECCS configuration, the advanced accumulator design and some of the injection performance and visualization test results. It was verified that the flow resistance of the advanced accumulator is independent of the model scale. The similarity law and performance data of the advanced accumulator for applying APWR was established. (author)

  14. Differential fat harvesting

    Directory of Open Access Journals (Sweden)

    Sebastian Torres Farr

    2014-12-01

    Full Text Available Aim: Volume replacement with fillers is regularly performed with the use of diverse volumetric materials to correct different structures around the face, depending on the volume enhancement required and the thickness of the soft tissue envelope. Differential fat harvesting and posterior grafting is performed to place the correct fat parcel size for each target area, expanding the potential applications of fat. Methods: Sixty patients consecutively recruited on a first come basis undergone a facial fat grafting procedure, in private practice setting between March 2012 and October 2013. Fat grafting quantity and quality was predicted for each case. Differential harvesting was performed, with 2 fat parcels size. Processing was performed through washing. Fat infiltration was carried out through small cannulas or needles depending on the treated area. Outcomes were analysed both by the physicians and the patients at 7 days, 1 month, 3 months and 6 months through a perceived satisfaction questionnaire. Parameters considered were downtime or discomfort, skin benefits, volume restoration, reabsorption rate estimated and overall improvement. Results: Full facial differential fat grafting procedure lasted an average of 1.5-2.5 h. Average downtime was 3-4 days. Follow-up was performed to a minimum of 6 months. Both patient and physician overall satisfaction rates were mostly excellent. Adverse events like lumps or irregularities were not encountered. Conclusion: Differential fat harvesting and posterior grafting is a valid alternative, to expand the repertoire of fat use, allow a more homogeneous effect, reduce the potential complications, speed up the process, improve graft survival, and to enhance overall aesthetic outcome.

  15. Abdominal wall fat pad biopsy

    Science.gov (United States)

    Amyloidosis - abdominal wall fat pad biopsy; Abdominal wall biopsy; Biopsy - abdominal wall fat pad ... is the most common method of taking an abdominal wall fat pad biopsy . The health care provider cleans the ...

  16. Hunger and Satiety Mechanisms and Their Potential Exploitation in the Regulation of Food Intake

    OpenAIRE

    Amin, Tehmina; Mercer, Julian G.

    2016-01-01

    Effective strategies to combat recent rises in obesity levels are limited. The accumulation of excess body fat results when energy intake exceeds that expended. Energy balance is controlled by hypothalamic responses, but these can be overridden by hedonic/reward brain systems. This override, combined with unprecedented availability of cheap, energy-dense, palatable foods, may partly explain the increase in overweight and obesity. The complexity of the processes that regulate feeding behaviour...

  17. The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise.

    Science.gov (United States)

    Cai, Ming; Wang, Hong; Li, Jing-Jing; Zhang, Yun-Li; Xin, Lei; Li, Feng; Lou, Shu-Jie

    2016-10-01

    High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models. Additionally, HFD that is associated with hyperglycemia could induce hippocampal ERS, thus impairing insulin signaling and cognitive health in HFD mice. One goal of this study was to determine whether hyperglycemia and hyperlipidemia could cause hippocampal ERS in HFD-induced obese SD rats, and explore the potential mechanisms of ERS regulating hippocampal BDNF and SYN proteins production. Additionally, although regular aerobic exercise could reduce central inflammation and elevate hippocampal BDNF and SYN levels in obese rats, the regulated mechanisms are poorly understood. Nrf2-HO-1 pathways play roles in anti-ERS, anti-inflammation and anti-apoptosis in peripheral tissues. Therefore, the other goal of this study was to determine whether aerobic exercise could activate Nrf2-HO-1 in hippocampus to alleviate obesity-induced hippocampal ERS, which would lead to increased BDNF and SYN levels. Male SD rats were fed on HFD for 8weeks to establish the obese model. Then, 8weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that HFD-induced obesity caused hyperglycemia and hyperlipidemia, and significantly promoted hippocampal glucose transporter 3 (GLUT3) and fatty acid transport protein 1 (FATP1) protein expression. These results were associated with the activation of hippocampal ERS and ERS-mediated apoptosis. At the same time, we found that excessive hippocampal ERS not only

  18. Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

    Science.gov (United States)

    Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

    2018-01-01

    Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Obese super athletes: fat-fueled migration in birds and bats.

    Science.gov (United States)

    Guglielmo, Christopher G

    2018-03-07

    Migratory birds are physiologically specialized to accumulate massive fat stores (up to 50-60% of body mass), and to transport and oxidize fatty acids at very high rates to sustain flight for many hours or days. Target gene, protein and enzyme analyses and recent -omic studies of bird flight muscles confirm that high capacities for fatty acid uptake, cytosolic transport, and oxidation are consistent features that make fat-fueled migration possible. Augmented circulatory transport by lipoproteins is suggested by field data but has not been experimentally verified. Migratory bats have high aerobic capacity and fatty acid oxidation potential; however, endurance flight fueled by adipose-stored fat has not been demonstrated. Patterns of fattening and expression of muscle fatty acid transporters are inconsistent, and bats may partially fuel migratory flight with ingested nutrients. Changes in energy intake, digestive capacity, liver lipid metabolism and body temperature regulation may contribute to migratory fattening. Although control of appetite is similar in birds and mammals, neuroendocrine mechanisms regulating seasonal changes in fuel store set-points in migrants remain poorly understood. Triacylglycerol of birds and bats contains mostly 16 and 18 carbon fatty acids with variable amounts of 18:2n-6 and 18:3n-3 depending on diet. Unsaturation of fat converges near 70% during migration, and unsaturated fatty acids are preferentially mobilized and oxidized, making them good fuel. Twenty and 22 carbon n-3 and n-6 polyunsaturated fatty acids (PUFA) may affect membrane function and peroxisome proliferator-activated receptor signaling. However, evidence for dietary PUFA as doping agents in migratory birds is equivocal and requires further study. © 2018. Published by The Company of Biologists Ltd.

  20. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

    Full Text Available Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulates health and lifespan.

  1. Know Your Fats

    Science.gov (United States)

    ... They're mainly found in fish such as salmon, trout and herring, avocados, olives, walnuts and liquid ... fats are found in many fried foods and baked goods such as pastries, pizza dough, pie crust, ...

  2. Facts about polyunsaturated fats

    Science.gov (United States)

    ... albacore tuna, and trout Corn oil Soybean oil Safflower oil To get the health benefits, you need to ... sunflower seeds to salads. Cook with corn or safflower oil instead of butter and solid fats.

  3. Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet.

    Science.gov (United States)

    Wan, Wenting; Li, Hongxiang; Xiang, Jiamei; Yi, Fan; Xu, Lijia; Jiang, Baoping; Xiao, Peigen

    2018-01-01

    Maca ( Lepidium meyenii Walpers) has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM) on high-fat, high-fructose diet (HFD)-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects. For 20 weeks, 6-week-old male golden hamsters were fed the following respective diets: (1) a standard diet, (2) HFD, (3) HFD supplemented with metformin, or (4) HFD supplemented with three doses of AEM (300, 600, or 1,200 mg/kg). After 20 weeks, the golden hamsters that received daily AEM supplementation presented with the beneficial effects of improved hyperlipidemia, hyperinsulinemia, insulin resistance, and hepatic steatosis in vivo . Based on the hepatic metabolomic analysis results, alterations in metabolites associated with pathological changes were examined. A total of 194 identified metabolites were mapped to 46 relative metabolic pathways, including those of energy metabolism. In addition, via in silico profiling for secondary maca metabolites by a joint pharmacophore- and structure-based approach, a compound-target-disease network was established. The results revealed that 32 bioactive compounds in maca targeted 16 proteins involved in metabolism disorder. Considering the combined metabolomics and virtual screening results, we employed quantitative real-time PCR assays to verify the gene expression of key enzymes in the relevant pathways. AEM promoted glycolysis and inhibited gluconeogenesis via regulating the expression of key genes such as Gck and Pfkm . Moreover, AEM upregulated tricarboxylic acid (TCA) cycle flux by changing the concentrations of intermediates and increasing the mRNA levels of Aco2 , Fh , and Mdh2 . In addition, the lipid

  4. Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet

    Directory of Open Access Journals (Sweden)

    Wenting Wan

    2018-04-01

    Full Text Available Maca (Lepidium meyenii Walpers has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM on high-fat, high-fructose diet (HFD-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects. For 20 weeks, 6-week-old male golden hamsters were fed the following respective diets: (1 a standard diet, (2 HFD, (3 HFD supplemented with metformin, or (4 HFD supplemented with three doses of AEM (300, 600, or 1,200 mg/kg. After 20 weeks, the golden hamsters that received daily AEM supplementation presented with the beneficial effects of improved hyperlipidemia, hyperinsulinemia, insulin resistance, and hepatic steatosis in vivo. Based on the hepatic metabolomic analysis results, alterations in metabolites associated with pathological changes were examined. A total of 194 identified metabolites were mapped to 46 relative metabolic pathways, including those of energy metabolism. In addition, via in silico profiling for secondary maca metabolites by a joint pharmacophore- and structure-based approach, a compound-target-disease network was established. The results revealed that 32 bioactive compounds in maca targeted 16 proteins involved in metabolism disorder. Considering the combined metabolomics and virtual screening results, we employed quantitative real-time PCR assays to verify the gene expression of key enzymes in the relevant pathways. AEM promoted glycolysis and inhibited gluconeogenesis via regulating the expression of key genes such as Gck and Pfkm. Moreover, AEM upregulated tricarboxylic acid (TCA cycle flux by changing the concentrations of intermediates and increasing the mRNA levels of Aco2, Fh, and Mdh2. In addition, the lipid

  5. Effect of dietary fat on hepatic liver X receptor expression in P-glycoprotein deficient mice: implications for cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Lee Stephen D

    2008-06-01

    Full Text Available Abstract Pgp (P-glycoprotein, MDR1, ABCB1 is an energy-dependent drug efflux pump that is a member of the ATP-binding cassette (ABC family of proteins. Preliminary studies have reported that nonspecific inhibitors of Pgp affect synthesis and esterification of cholesterol, putatively by blocking trafficking of cholesterol from the plasma membrane to the endoplasmic reticulum, and that relative increases in Pgp within a given cell type are associated with increased accumulation of cholesterol. Several key efflux proteins involved in the cholesterol metabolic pathway are transcriptionally regulated by the nuclear hormone liver X receptor (LXR. Therefore, to examine the interplay between P-glycoprotein and the cholesterol metabolic pathway, we utilized a high fat, normal cholesterol diet to upregulate LXRα without affecting dietary cholesterol. Our research has demonstrated that mice lacking in P-glycoprotein do not exhibit alterations in hepatic total cholesterol storage, circulating plasma total cholesterol levels, or total cholesterol concentration in the bile when compared to control animals on either a normal (25% calories from dietary fat or high fat (45% calories from dietary fat diet. However, p-glycoprotein deficient mice (Mdr1a-/-/1b-/- exhibit increased hepatic LXRα protein expression and an elevation in fecal cholesterol concentration when compared to controls.

  6. Alternative fat sources to animal fat for pigs

    DEFF Research Database (Denmark)

    Lauridsen, Charlotte; Christensen, Thomas Bruun; Halekoh, Ulrich

    2007-01-01

    % of either animal fat, palm oil mix, palm oil, vegetable oil mix, coconut oil, or rapeseed oil were tested in weaned and growing pigs. It was concluded that several vegetable fat sources (palm oil mix, palm oil, coconut oil, rapeseed oil) could be used as alternatives to animal fat in pig feed, whereas fat......The use of fats and oils in diets for pigs is of great importance due to their high energy value. As a consequence of the BSE-crisis in the European Union, the amount of animal fat available for animal feeds has been reduced, and alternative fat sources are of increasing importance. In this paper...

  7. Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages.

    Science.gov (United States)

    Tarabra, Elena; An Lee, Ting-Wen; Zammit, Victor A; Vatish, Manu; Yamada, Eijiro; Pessin, Jeffrey E; Bastie, Claire C

    2017-10-17

    Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency ( fynKO ) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in fynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of adipose tissue stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats.

  8. Microbial accumulation of uranium

    International Nuclear Information System (INIS)

    Zhang Wei; Dong Faqin; Dai Qunwei

    2005-01-01

    The mechanism of microbial accumulation of uranium and the effects of some factors (including pH, initial uranium concentration, pretreatment of bacteria, and so on) on microbial accumulation of uranium are discussed briefly. The research direction and application prospect are presented. (authors)

  9. Accumulative capabilities of essential nutrient elements in organs of ...

    African Journals Online (AJOL)

    use

    2011-11-23

    Nov 23, 2011 ... Cu > Mn > Zn > B. In conclusion, the ACs for essential nutrient elements differed, with the ... and Fe were quantified using Perkin Elmer Atomic Absorption .... vitamin C, protein and fat ranging from 249.6 to 266 .... Boron determination in plant tissues by ... Accumulation of cadmium and selected elements.

  10. Phospholipase C-related catalytically inactive protein can regulate obesity, a state of peripheral inflammation

    Directory of Open Access Journals (Sweden)

    Yosuke Yamawaki

    2017-02-01

    Full Text Available Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL-cholesterol, and high-density lipoprotein (HDL-cholesterol. Prevention and control of obesity is complex, and requires a multifaceted approach. The elucidation of molecular mechanisms driving fat metabolism (adipogenesis and lipolysis aims at developing clinical treatments to control obesity. We recently reported a new regulatory mechanism in fat metabolism: a protein phosphatase binding protein, phospholipase C-related catalytically inactive protein (PRIP, regulates lipolysis in white adipocytes and heat production in brown adipocytes via phosphoregulation. Deficiency of PRIP in mice led to reduced fat accumulation and increased energy expenditure, resulting in a lean phenotype. Here, we evaluate PRIP as a new therapeutic target for the control of obesity.

  11. Fat digestion and absorption in spice-pretreated rats.

    Science.gov (United States)

    Prakash, Usha N S; Srinivasan, Krishnapura

    2012-02-01

    A few common spices are known to stimulate secretion of bile with higher amount of bile acids which play a major role in digestion and absorption of dietary lipids. It would be appropriate to verify if these spices enable efficient digestion and absorption during high-fat intake. In this context, dietary ginger (0.05%), piperine (0.02%), capsaicin (0.015%), and curcumin (0.5%) were examined for their influence on bile secretion, digestive enzymes of pancreas and absorption of dietary fat in high-fat (30%) fed Wistar rats for 8 weeks. These spices enhanced the activity of pancreatic lipase, amylase, trypsin and chymotrypsin by 22-57%, 32-51%, 63-81% and 12-38%, respectively. Dietary intake of spices along with high-fat enhanced fat absorption. These dietary spices increased bile secretion with higher bile acid content. Stimulation of lipid mobilisation from adipose tissue was suggested by the decrease in perirenal adipose tissue weight by dietary capsaicin and piperine. This was also accompanied by prevention of the accumulation of triglyceride in liver and serum in high-fat fed rats. Activities of key lipogenic enzymes in liver were reduced which was accompanied by an increased activity of hormone-sensitive lipase. Thus, dietary ginger and other spice compounds enhance fat digestion and absorption in high-fat fed situation through enhanced secretion of bile salts and a stimulation of the activity pancreatic lipase. At the same time, the energy expenditure is facilitated by these spices to prevent the accumulation of absorbed fat. Copyright © 2011 Society of Chemical Industry.

  12. Ghrelin receptor null mice have reduced visceral fat and improved insulin sensitivity during aging

    Science.gov (United States)

    Aging is associated with a higher incidence of Type 2 diabetes; one in five Americans over age 65 has diabetes. Loss of lean mass and accumulation of fat, particularly visceral fat, during aging result in increased insulin resistance. Insulin resistance is a major pathogenic factor for Type 2 diabet...

  13. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat - functional implications

    NARCIS (Netherlands)

    Kreier, Felix; Fliers, Eric; Voshol, Peter J.; van Eden, Corbert G.; Havekes, Louis M.; Kalsbeek, Andries; van Heijningen, Caroline L.; Sluiter, Arja A.; Mettenleiter, Thomas C.; Romijn, Johannes A.; Sauerwein, Hans P.; Buijs, Ruud M.

    2002-01-01

    The wealth of clinical epidemiological data on the association between intra-abdominal fat accumulation and morbidity sharply contrasts with the paucity of knowledge about the determinants of fat distribution, which cannot be explained merely in terms of humoral factors. If it comes to neuronal

  14. Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people.

    Science.gov (United States)

    Kang, Seon Mee; Yoon, Ji Won; Ahn, Hwa Young; Kim, So Yeon; Lee, Kyoung Ho; Shin, Hayley; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

    2011-01-01

    Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm(2) and 126.9±55.2 cm(2) in men (P = 0.045) and 120.0±46.7 cm(2) and 211.8±65.9 cm(2) in women (Pandroid and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both Pandroid fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution.

  15. Brain fat embolism

    International Nuclear Information System (INIS)

    Sugiura, Yoshihiro; Kawamura, Yasutaka; Suzuki, Hisato; Yanagimoto, Masahiro; Goto, Yukio

    1994-01-01

    Recently CT and MR imaging have demonstrated that cerebral edema is present in cases of fat embolism syndrome. To simulate this we have made a model of brain-fat embolism in rats under MR imaging. In 20 rats, we did intravenous injection of heparinized blood, 1.5 ml·kg -1 taken from femoral bone marrow cavity. Twenty four hours after the injection, we examined the MR images (1.5 tesla, spin-echo method) of brains and histologic findings of brains and lungs were obtained. In 5 of 20 rats, high signal intensity on T2-weighted images and low signal intensity on T1-weighted images were observed in the area of the unilateral cerebral cortex or hippocampus. These findings showed edema of the brains. They disappeared, however, one week later. Histologic examinations showed massive micro-fat emboli in capillaries of the deep cerebral cortex and substantia nigra, but no edematous findings of the brain were revealed in HE staining. In pulmonary arteries, we also found large fat emboli. We conclude that our model is a useful one for the study of brain fat embolism. (author)

  16. Joint water-fat separation and deblurring for spiral imaging.

    Science.gov (United States)

    Wang, Dinghui; Zwart, Nicholas R; Pipe, James G

    2018-06-01

    Most previous approaches to spiral Dixon water-fat imaging perform the water-fat separation and deblurring sequentially based on the assumption that the phase accumulation and blurring as a result of off-resonance are separable. This condition can easily be violated in regions where the B 0 inhomogeneity varies rapidly. The goal of this work is to present a novel joint water-fat separation and deblurring method for spiral imaging. The proposed approach is based on a more accurate signal model that takes into account the phase accumulation and blurring simultaneously. A conjugate gradient method is used in the image domain to reconstruct the deblurred water and fat iteratively. Spatially varying convolutions with a local convergence criterion are used to reduce the computational demand. Both simulation and high-resolution brain imaging have demonstrated that the proposed joint method consistently improves the quality of reconstructed water and fat images compared with the sequential approach, especially in regions where the field inhomogeneity changes rapidly in space. The loss of signal-to-noise-ratio as a result of deblurring is minor at optimal echo times. High-quality water-fat spiral imaging can be achieved with the proposed joint approach, provided that an accurate field map of B 0 inhomogeneity is available. Magn Reson Med 79:3218-3228, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  17. Analysis of Trans Fat in Edible Oils with Cooking Process

    Science.gov (United States)

    Song, Juhee; Park, Joohyeok; Jung, Jinyeong; Lee, Chankyu; Gim, Seo Yeoung; Ka, HyeJung; Yi, BoRa; Kim, Mi-Ja; Kim, Cho-il

    2015-01-01

    Trans fat is a unsaturated fatty acid with trans configuration and separated double bonds. Analytical methods have been introduced to analyze trans fat content in foods including infrared (IR) spectroscopy, gas chromatography (GC), Fourier transform-infrared (FT-IR) spectroscopy, reverses-phase silver ion high performance liquid chromatography, and silver nitrate thin layer chromatography. Currently, FT-IR spectroscopy and GC are mostly used methods. Trans fat content in 6 vegetable oils were analyzed and processing effects including baking, stir-frying, pan-frying, and frying on the formation of trans fat in corn oil was evaluated by GC. Among tested vegetable oils, corn oil has 0.25 g trans fat/100 g, whereas other oils including rapeseed, soybean, olive, perilla, and sesame oils did not have detectable amount of trans fat content. Among cooking methods, stir-frying increased trans fat in corn oil whereas baking, pan-frying, and frying procedures did not make changes in trans fat content compared to untreated corn oils. However, the trans fat content was so low and food label can be declared as ‘0’ trans based on the regulation of Ministry of Food ad Drug Safety (MFDS) (edible oil). PMID:26483890

  18. The Body Fat-Cognition Relationship in Healthy Older Individuals: Does Gynoid vs Android Distribution Matter?

    Science.gov (United States)

    Forte, R; Pesce, C; De Vito, G; Boreham, C A G

    2017-01-01

    To examine the relationship between regional and whole body fat accumulation and core cognitive executive functions. Cross-sectional study. 78 healthy men and women aged between 65 and 75 years recruited through consumer's database. DXA measured percentage total body fat, android, gynoid distribution and android/gynoid ratio; inhibition and working memory updating through Random Number Generation test and cognitive flexibility by Trail Making test. First-order partial correlations between regional body fat and cognitive executive function were computed partialling out the effects of whole body fat. Moderation analysis was performed to verify the effect of gender on the body fat-cognition relationship. Results showed a differentiated pattern of fat-cognition relationship depending on fat localization and type of cognitive function. Statistically significant relationships were observed between working memory updating and: android fat (r = -0.232; p = 0.042), gynoid fat (r = 0.333; p = 0.003) and android/gynoid ratio (r = -0.272; p = 0.017). Separating genders, the only significant relationship was observed in females between working memory updating and gynoid fat (r = 0.280; p = 0.045). In spite of gender differences in both working memory updating and gynoid body fat levels, moderation analysis did not show an effect of gender on the relationship between gynoid fat and working memory updating. Results suggest a protective effect of gynoid body fat and a deleterious effect of android body fat. Although excessive body fat increases the risk of developing CDV, metabolic and cognitive problems, maintaining a certain proportion of gynoid fat may help prevent cognitive decline, particularly in older women. Guidelines for optimal body composition maintenance for the elderly should not target indiscriminate weight loss, but weight maintenance through body fat/lean mass control based on non-pharmacological tools such as physical exercise, known to have protective effects

  19. Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation.

    Science.gov (United States)

    Chen, Fan; Chen, Dandan; Zhao, Xinmei; Yang, Shuai; Li, Zhe; Sanchis, Daniel; Jin, Liang; Qiang, Xizhe; Wang, Kaiye; Xu, Yitao; Zhang, Yubin; Ye, Junmei

    2017-12-01

    Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity.

    Directory of Open Access Journals (Sweden)

    Kirsi H Pietiläinen

    2008-03-01

    Full Text Available The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background.We used a special study design of "clonal controls," rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white, with a mean +/- standard deviation (SD age 25.8 +/- 1.4 y and a body mass index (BMI difference 5.2 +/- 1.8 kg/m(2. Sequence analyses of mitochondrial DNA (mtDNA in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA catabolism (p < 0.0001. In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025. Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults.Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance.

  1. Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

    Science.gov (United States)

    Lee, Yong‐Soo; Kim, Ja‐Yeon; Oh, Kyung‐Soo

    2017-01-01

    Abstract Background Fatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid‐binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model. Methods In the RCT model, we evaluated the expression of FABP4 by qRT‐PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia‐inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively. Results FABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear‐induced FABP4 expression was up‐regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter

  2. Histological changes associated with mesotherapy for fat dissolution.

    Science.gov (United States)

    Rose, Paul T; Morgan, Michael

    2005-03-01

    Mesotherapy is a form of medical therapy popular in Europe and South America. It is used for treating a variety of medical conditions, including the treatment of localized fat deposits and cellulite. Phosphatidylcholine/deoxycholate injections are a popular technique to treat localized fat accumulations and have recently become synonymous with mesotherapy, although their history and technique are distinct. To treat localized fat deposits, phosphatidylcholine (PC) and deoxycholate (DC) are utilized. To date, there have been no published histological studies that explain the mechanism of action of PC and DC.Method. In this study the authors have obtained skin biopsies from a patient who had undergone mesotherapy with PC and DC. Punch biopsies were taken at one and two weeks after the procedure.Results. Each of the biopsies taken at one and two weeks after treatment with PC and DC showed a normal epithelium and dermis, with a mixed septal and lobular panniculitis. The fat lobules were infiltrated by increased numbers of lymphocytes and, in particular, macrophages. The macrophages consisted of conventional forms, foam cells, and multinucleated fat-containing giant cells. The inflammation was associated with serous atrophy and microcyst formation.Conclusion. This study demonstrates that mesotherapy with PC and DC affects the subcutaneous fat. We theorize that the reduction of subcutaneous fat likely follows inflammatory-mediated necrosis and resorption.

  3. Subcutaneous encapsulated fat necrosis

    DEFF Research Database (Denmark)

    Aydin, Dogu; Berg, Jais O

    2016-01-01

    We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help...

  4. Fats for diabetics. (Letter).

    NARCIS (Netherlands)

    Katan, M.B.

    1994-01-01

    Opinion. Comments on the treatment of type 2 diabetes from the interaction between nature and nurture. Effective form of treatment for type 2 diabetes; Composition of the diet for diabetics; Identification of unsaturated fats in the diabetic diet; Risks faced by diabetic patients.

  5. That Fat Cat

    Science.gov (United States)

    Lambert, Phyllis Gilchrist

    2012-01-01

    This activity began with a picture book, Nurit Karlin's "Fat Cat On a Mat" (HarperCollins; 1998). The author and her students started their project with a 5-inch circular template for the head of their cats. They reviewed shapes as they drew the head and then added the ears and nose, which were triangles. Details to the face were added when…

  6. Intra-abdominal fat: Comparison of computed tomography fat ...

    African Journals Online (AJOL)

    Background: Intra-abdominal fat is an important factor in determining the metabolic syndrome/insulin resistance, and thus the risk of diabetes and ischaemic heart disease. Computed Tomography (CT) fat segmentation represents a defined method of quantifying intra-abdominal fat, with attendant radiation risks.

  7. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects.

    Science.gov (United States)

    Haufe, Sven; Engeli, Stefan; Kast, Petra; Böhnke, Jana; Utz, Wolfgang; Haas, Verena; Hermsdorf, Mario; Mähler, Anja; Wiesner, Susanne; Birkenfeld, Andreas L; Sell, Henrike; Otto, Christoph; Mehling, Heidrun; Luft, Friedrich C; Eckel, Juergen; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens

    2011-05-01

    Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet. Copyright © 2011 American Association for the Study of Liver Diseases.

  8. Figuring Out Fat and Calories

    Science.gov (United States)

    ... our growth and activities — everything from solving a math problem to racing up and down the soccer ... saturated fat and trans fat raise blood cholesterol levels, increasing a person's chances of developing heart disease, ...

  9. High-fat diet decreases energy expenditure and expression of genes controlling lipid metabolism, mitochondrial function and skeletal system development in the adipose tissue, along with increased expression of extracellular matrix remodelling- and inflammation-related genes.

    Science.gov (United States)

    Choi, Myung-Sook; Kim, Young-Je; Kwon, Eun-Young; Ryoo, Jae Young; Kim, Sang Ryong; Jung, Un Ju

    2015-03-28

    The aim of the present study was to identify the genes differentially expressed in the visceral adipose tissue in a well-characterised mouse model of high-fat diet (HFD)-induced obesity. Male C57BL/6J mice (n 20) were fed either HFD (189 % of energy from fat) or low-fat diet (LFD, 42 % of energy from fat) for 16 weeks. HFD-fed mice exhibited obesity, insulin resistance, dyslipidaemia and adipose collagen accumulation, along with higher levels of plasma leptin, resistin and plasminogen activator inhibitor type 1, although there were no significant differences in plasma cytokine levels. Energy intake was similar in the two diet groups owing to lower food intake in the HFD group; however, energy expenditure was also lower in the HFD group than in the LFD group. Microarray analysis revealed that genes related to lipolysis, fatty acid metabolism, mitochondrial energy transduction, oxidation-reduction, insulin sensitivity and skeletal system development were down-regulated in HFD-fed mice, and genes associated with extracellular matrix (ECM) components, ECM remodelling and inflammation were up-regulated. The top ten up- or down-regulated genes include Acsm3, mt-Nd6, Fam13a, Cyp2e1, Rgs1 and Gpnmb, whose roles in the deterioration of obesity-associated adipose tissue are poorly understood. In conclusion, the genes identified here provide new therapeutic opportunities for prevention and treatment of diet-induced obesity.

  10. Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease.

    Directory of Open Access Journals (Sweden)

    Koro Gotoh

    Full Text Available Obesity is associated with systemic low-grade inflammation and is a risk factor for non-alcoholic fatty pancreas disease (NAFPD, but the molecular mechanisms of these associations are not clear. Interleukin (IL-10, a potent anti-inflammatory cytokine, is released during acute pancreatitis and is known to limit inflammatory responses by downregulating the release of proinflammatory mediators. The origin of IL-10 that suppresses pancreatitis has not been investigated. Since obesity is known to reduce expression of proinflammatory cytokines in the spleen, we examined whether spleen-derived IL-10 regulates NAFPD caused by high-fat (HF diet-induced obesity. The following investigations were performed: 1 IL-10 induction from spleen was examined in male mice fed a HF diet; 2 triglyceride content, expression of pro- and anti-inflammatory cytokines and infiltration of M1 and M2 macrophages were determined to evaluate ectopic fat accumulation and inflammatory responses in the pancreas of splenectomy (SPX-treated mice fed HF diet; 3 exogenous IL-10 was systemically administered to SPX-treated obese mice and the resulting pathogenesis caused by SPX was assessed; and 4 IL-10 knockout (IL-10KO mice were treated with SPX and ectopic fat deposition and inflammatory conditions in the pancreas were investigated. Obesity impaired the ability of the spleen to synthesize cytokines, including IL-10. SPX aggravated fat accumulation and inflammatory responses in the pancreas of HF diet-induced obese mice and these effects were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on fat deposition and inflammatory responses in the pancreas of IL-10KO mice. Our findings indicate that obesity reduces IL-10 production by the spleen and that spleen-derived IL-10 may protect against the development of NAFPD.

  11. Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet

    Directory of Open Access Journals (Sweden)

    Romeo B. Batacan, Jr

    2018-01-01

    Conclusion: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation, mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.

  12. Optimize fat Replacers in food

    Directory of Open Access Journals (Sweden)

    M HassaniMoosaAbadi

    2018-03-01

    CONCLUSION: In order to solve some problems related to the elimination or reduction of fat , cardiovascular diseases prevention and health improvement, it is possible to use fat alternatives in communities’ food, furthermore, the obtained results indicated that the production of low-calorie foods is similar to the texture of high fat products.

  13. Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5.

    Science.gov (United States)

    Gao, Xing; Nan, Yang; Zhao, Yuanlin; Yuan, Yuan; Ren, Bincheng; Sun, Chao; Cao, Kaiyu; Yu, Ming; Feng, Xuyang; Ye, Jing

    2017-12-01

    Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. In this study, we observed that atorvastatin moderately reduced the expression of Plin5 in livers without changing the protein level of Plin5 in the hepatic LD fraction of mice fed with high-fat diet (HFD). Intriguingly, atorvastatin stimulated the PKA-mediated phosphorylation of Plin5 and reduced the triglyceride (TG) accumulation in hepatocytes with overexpression of wide type (Plin5-WT) compared to serine-155 mutant Plin5 (Plin5-S155A). Moreover, PKA-stimulated FA release of purified LDs carrying Plin5-WT but not Plin5-S155A. Glucagon, a PKA activator, stimulated the phosphorylation of Plin5-WT and inhibited its interaction with CGI-58. The results indicated that atorvastatin promoted lipolysis and reduced TG accumulation in the liver by increasing PKA-mediated phosphorylation of Plin5. This new mechanism of lipid-lowering effects of atorvastatin might provide a new strategy for NAFLD treatment. Copyright © 2017. Published by Elsevier B.V.

  14. Ectopic Fat and Insulin Resistance: Pathophysiology and Effect of Diet and Lifestyle Interventions

    Directory of Open Access Journals (Sweden)

    M. Snel

    2012-01-01

    Full Text Available The storage of triglyceride (TG droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM. Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.

  15. Accumulation by Conservation

    NARCIS (Netherlands)

    Büscher, Bram; Fletcher, Robert

    2015-01-01

    Following the financial crisis and its aftermath, it is clear that the inherent contradictions of capitalist accumulation have become even more intense and plunged the