Objective: Pomegranate, (Punica granatum L., Lythraceae) peel has concentrated amounts of lipid-lowering elements that demonstrated, in various hoary and recent studies, their effects against obesity and hyperlipidemia, which involves elevated rates of lipid and lipoprotein levels in blood and increases risks of cardiovascular diseases.We aim to study expression modulation of genes involved in lipid metabolism by the impact of standardized pomegranate peel extract (PPE) in a comprehensive research on human liver cells and experimental mice.Methods: Using reverse-transcription real-time PCR, an in vitro study harnessing HepG2 cell line was conducted to determine the hyperlipidemia-related gene expression profiles and cytotoxic effects upon treatment with PPE. In another complementary in vivo study, male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with PPE for 14 d to define the expression of lipid metabolism related genes that control obesity. Fatty liver proportions were also estimated after treatment.Results: Higher mRNA expression of LDL receptor (LDL-R) and down-regulation of sterol regulatory element-binding protein (SREBF-2), (SRBEP-1c), Fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) upon PPE treatment in HepG2 cell line were significantly recorded. In vivo study indicated significant weight reduction of body and liver, besides amelioration of fatty liver state detected by histological analysis. Moreover, the reverse-transcription real-time PCR assay demonstrated suppression (FAS) expression and up regulation of hormone sensitive lipase (HSL) in mice isolated liver and white adipose tissues.Conclusion: Our study manages to affirm the hypolipidemic and anti-fatty liver influence of Punica granatum L. peel extract, reflected by molecular evaluation above and beyond other physiological assays.Keywords: Pomegranate, Peel extract, Hyperlipidemia, LDLR, SREBP, FAS, HMGCR, HS
