Browning the Fat May Reset the Metabolome: Role of PPAR [gamma] Network of Genes in Obesity and Cardiovascular Diseases

Abstract

Obesity is a major global health problem; its associated metabolic-induced disorders have been the spotlight of modern life and contemporary research. The quality of fat and its distribution in the fabric of adipose through age and development can influence the overall metabolism in the body. The imbalance in brown fat ratio compared to white fat in the body could be the consequence or the driving force of metabolism associated with inflammation, diabetes mellitus, cardiovascular diseases (CVDs) and other chronic non- communicable diseases (NCDs), including cancers. In either case, the brown fat is a healthier and likely factor in diverting many metabolic disturbances. This review explores current research emphasizing and elucidating the positive role of brown fat as a possible candidate for enrichment and amelioration in obesity-associated metabolic diseases, including inflammation, diabetes and CVDs. Furthermore, the review tries to gather some specific information on constellation of candidate genes and molecules that play clear roles in browning the fat. With supportive research and educated deductions, this study highlights the peroxisome proliferator-activated receptor gamma (PPARy) network of gene interactions with transforming growth factor beta (TGF-ß) and tumor necrosis factor alpha (TNF-a) as major performers in metabolic harmony. The cross-talk mediators between such major players are done through many smaller molecules and proteins such as forkhead box protein C2 (FOXC2) and PRDM16 transcriptional regulators and thermogenic genes; uncoupling protein 1 (UCP1) and peroxisome proliferatoractivated receptor gamma coactivator 1-alpha (PGC-1a) regulates thermogenesis and (brown adipose tissue) BAT development. The review concludes that the central metabolome genes of PPARy, TNF-a and TGF-ß are interconnected and that rebooting the PPARy central network of genes will rebalance the storage of fats and its consumption. Several clinical and preclinical studies have demonstrated the beneficial effects of PPAR ligands on various cardiovascular risk factors as well.