European Journal of Biomedical and Pharmaceutical Sciences

FUNCTIONAL GENOMICS: MICRO RNA IN LIPID METABOLISM AND OBESITY

C. Justin David* and G. Kumaresan

ABSTRACT

Obesity has become a pandemic afflicting global population, irrespective of socio-economic status. Considered the master disorder, culminates in Type 2 Diabetes Mellitus (T2DM), Non-alcoholic Fatty liver disease (NAFLD), Non-alcoholic Steatohepatitis (NASH), hypertension and several cardiovascular diseases (CVDs). Dietary lipids contribute significantly to diet-induced obesity therefore, lipid metabolism requires regulation at the cellular level by intra-cellular regulatory networks from the influence of intrinsic and environmental factors on metabolic homeostasis, which is essential for physiological wellbeing. Increased levels of low density lipoproteins (LDLs), Cholesterol and Triglycerides (TGs) alters lipid levels thereby altering tissue-specific gene expression in human pathologies. Aberrant lipid metabolism, dysregulated Sterol Regulatory Element Binding Proteins (SREBPs) and Liver X receptors (LXRs) were so far cited as major reasons attributing to obesity. Recently, regulation of cholesterol and fatty acid metabolism by Small non coding RNAs (SncRNAs) such as Micro RNAs (miRNAs) were confirmed in worms, rodents and mammalian models. A long list of miRNAs with tissue specific expression (miR-33 family, miR-27, miR-122, miR-370, miR-335, miR-143, miR-378 and miR-125 family) had been suggested to play a crucial role in lipid metabolism. Our understanding of the molecular mechanism of post-transcriptional regulation of cellular homeostasis and functional genomics of miRNAs in regulation of genes involved in non-communicable metabolic disorders like obesity, NAFLD, non-alcoholic steato-hepatosis (NASH) and Hepato-Cellular Carcinoma (HCC) remains obscure. This review addresses post-transcriptional regulation of lipid metabolism by miRNAs, key targets and beneficial applications for developing targeted therapeutics in humans.

Keywords: obesity, dietary lipids, SncRNAs, miRNAs, lipid metabolism, SREBPs, post-transcriptional regulation, metabolic homeostasis, gene silencing.