%0 Journal Article
%T Grape Seed Proanthocyanidin Rescues Rats from Steatosis: A Comparative and Combination Study with Metformin
%A Baskaran Yogalakshmi
%A S Sreeja
%A Rajagopalan Geetha
%A Mutlur Krishnamoorthy Radika
%A Carani Venkatraman Anuradha
%J Journal of Lipids
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/153897
%X 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-¦Á (PPAR-¦Á). 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-¦Á 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. 1. Introduction Nonalcoholic fatty liver disease (NAFLD) has become a global health problem in both adults and children, the prevalence of which has doubled during last 20 years in tune with the increasing incidence of obesity and insulin resistance [1]. Improper regulation of lipogenesis and lipid oxidation is a prime factor in the genesis of fatty liver. Lipogenesis encompasses the processes of fatty acid synthesis and subsequent formation of triglyceride (TG). Sterol regulatory elemental binding protein-1c (SREBP-1c) belongs to a family of transcription factors that are sensitive to cellular availability of cholesterol [2] and promotes fatty acid synthesis and lipid deposition. SREBP-1c regulates lipogenesis by increasing the expression of genes involved in fatty acid biosynthesis such as acetyl CoA carboxylase, fatty acid synthase, and stearoyl CoA desaturase. SREBP-1c has been implicated in the development of human metabolic disorders like obesity, type 2 diabetes, dyslipidemia, atherosclerosis, lipodystrophy, and metabolic syndrome. Lipid reserves are stored in the form of lipid droplets (LDs) intracellularly. LDs, long considered as inert substances, are now recognized for their dynamic role in lipid metabolism. They are structurally similar to circulating lipoproteins,
%U http://www.hindawi.com/journals/jl/2013/153897/