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Grape seed proanthocyanidin rescues rats from steatosis: a comparative and combination study with metformin.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD), a premorbid condition, lacks proper management owing to multitude of abnormalities. In this study, we compared the effects of a potent antioxidant, grape seed proanthocyanidins (GSP), and an insulin sensitizer, metformin (MET), in high-fat-fructose-diet- (HFFD-) induced albino Wistar rat model of NAFLD. Either GSP (100?mg/Kg b.w) or MET (50?mg/Kg b.w) or both were administered as therapeutic options. HFFD-fed rats showed abnormal plasma lipid profile, inflammation, and steatosis of the liver when examined by biochemical and histology techniques. Increased lipid storage, lipogenesis, and reduced lipolysis were evident from mRNA expression studies of hepatic lipid droplets (LD) proteins, sterol regulatory element binding 1c (SREBP 1c), and peroxisome proliferator activated receptor- ? (PPAR- ? ). GSP administration to HFFD-fed rats caused 69% reduction in hepatic TG levels, whereas MET caused only 23%. The combination treatment reduced TG levels by 63%. GSP reduced the mRNA expression of SREBP1c and LD proteins and increased that of PPAR- ? more effectively compared to MET in HFFD-induced hyperlipidemic rats. Combination of MET and GSP improved the metabolism of lipids effectively, but the effect was not additive in restoring lipid levels.

SUBMITTER: Yogalakshmi B

PROVIDER: S-EPMC3836386 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Grape seed proanthocyanidin rescues rats from steatosis: a comparative and combination study with metformin.

Yogalakshmi Baskaran B Sreeja S S Geetha Rajagopalan R Radika Mutlur Krishnamoorthy MK Anuradha Carani Venkatraman CV

Journal of lipids 20131106

Nonalcoholic fatty liver disease (NAFLD), a premorbid condition, lacks proper management owing to multitude of abnormalities. In this study, we compared the effects of a potent antioxidant, grape seed proanthocyanidins (GSP), and an insulin sensitizer, metformin (MET), in high-fat-fructose-diet- (HFFD-) induced albino Wistar rat model of NAFLD. Either GSP (100 mg/Kg b.w) or MET (50 mg/Kg b.w) or both were administered as therapeutic options. HFFD-fed rats showed abnormal plasma lipid profile, in ...[more]

PMID: 24307947

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Project description:White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity. The aim of this study was to determine whether grape seed proanthocyanidin extract (GSPE) can modulate WAT expandability. Because GSPE also contains gallic acid, we also studied the capacity of gallic acid to remodel WAT.Male Wistar rats were fed a standard chow diet (n=6) or a cafeteria diet (CAF) for 11 weeks. After 8 weeks, the CAF-fed animals were supplemented with 25?mg GSPE/kg body weight (n=6), 7?mg gallic acid/kg body weight (n=6) or the vehicle (n=6) for 3 weeks. Histological analyses were performed in the retroperitoneal (rWAT) and inguinal (iWAT) WAT to determine adipocyte size and number. Specific markers for adipogenesis and WAT functionality were analysed in rWAT using quantitative RT-PCR.GSPE or gallic acid supplementation did not reduce weight gain or reverse and adiposity. However, GSPE reduced adipocyte size significantly in rWAT and moderately in iWAT and tripled the adipocyte number in rWAT. Gallic acid slightly reduced adipocyte size in rWAT and iWAT and doubled the adipocyte number in both WATs. In accordance with this adipogenic activity, Pref-1 and PPAR? tended to be overexpressed in rWAT of rats supplemented with GSPE. Moreover, GSPE supplementation increased Plin1 and Fabp4 expression and restored adiponectin expression completely, indicating a better functionality of visceral WAT.GSPE supplementation has anti-hypertrophic and hyperplasic activities in rats with established obesity, mainly in visceral WAT inducing a healthier expansion of WAT to match the surplus energy provided by the cafeteria diet.

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Grape seed proanthocyanidin rescues rats from steatosis: a comparative and combination study with metformin.

Publications

Grape seed proanthocyanidin rescues rats from steatosis: a comparative and combination study with metformin.

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