Abstract
MiR-33a and miR-122 are major regulators of lipid metabolism in the liver and their deregulation has been linked to the development of metabolic diseases such as obesity and metabolic syndrome. The aim of this study was to evaluate whether the level of miR-33a and miR-122 in rat liver correlate with obesity and potential anti-obesity effect of grape seed extract (GSE) and calorie restricted diet with special emphasis on dyslipidemia, oxidative stress and inflammation. Rats received high fat diet (HFD) for four months to induce obesity. Animals which had ≥30% increase in body weight were selected in this study. Obese rats were divided into 4 groups (n=12/each) and treated for 8 weeks with caloric restriction, GSE (30 mg/kg daily orally) alone or in combined form. Obese rats developed increased body weight and up-regulation of miR-33a and mir-122 in the liver. Also obesity provoked dyslipidemia, oxidative stress and inflammatory status. Importantly, GSE alleviated all deleterious effects of HFD especially when administered with calorie restricted diet. They counteracted the increase of these two miRNAs with improvement in dyslipidemia, oxidative and inflammatory processes. The results reported suggested that beneficial metabolic effects of GSE in combination with dietary treatment could be useful to treat obesity and metabolic disorders. Key words: Obesity, GSE, dyslipidemia, oxidative stress, hepatic miRNAs
Highlights
Obesity is a public health concern characterized by excessive fat deposition into adipocytes and non-adipose tissues, which is accompanied by a cluster of chronic metabolic disorders, including cardiovascular diseases, type 2 diabetes, steatohepatitis and dyslipidemia
The obese rats were trained to lick suspension of gum acacia in distilled water (1 ml) which was used as the vehicle and randomly divided into four groups: Obese control (OC; n=12, kept on normal chow diet), calorie restricted group (CR; n=12), 25% food restriction of commercial chow) (Luvizotto et al, 2010), gervital group (Ger; n=12 receiving grape seed extract (GSE) 30 mg/kg daily orally dissolved in distilled water using gum acacia as suspending agent kept in normal chow diet) and calorie restricted + gervital group (CR + Ger; n=12) for 8 weeks
Body weight increased significantly in obese group by 158.2% after four months high fat diet compared to NC group while significant decreases were observed after 8 weeks in the CR, Ger either individually or in combination by 32, 31 and 50.6%, respectively compared to OC animals and CR + Ger group showed a significant reduction by 27% than CR only (P
Summary
Obesity is a public health concern characterized by excessive fat deposition into adipocytes and non-adipose tissues, which is accompanied by a cluster of chronic metabolic disorders, including cardiovascular diseases, type 2 diabetes, steatohepatitis and dyslipidemia. Obesity and metabolic disorders are linked to an overt oxidative stress and chronic inflammatory status. Oxidative stress along with a decline in antioxidant.
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