Repercussions of hepatic actions of glucagon and FGF21 in nonalcoholic fatty liver disease in HepG2 cells

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an emerging concern because of its increased prevalence. This disease, caused by high food intake, corresponds to the accumulation of fat in the liver ranging from a simple steatosis to a steatohepatitis. NAFLD has been correlated with disorders such as obesity, insulin resistance and type 2 diabetes mellitus (DM2), which may be associated with a sedentary lifestyle. Individuals with NAFLD usually have fasting hyperglucagonemia, indicating glucagon resistance that is generated by steatosis. As well, NAFLD has been related to the disruption of microRNAs, such as miR149 and miR212 that act on FGF21 degradation, favoring lipogenesis. However, studies indicate that physical exercises, moreover to promote glucagon secretion, they also have the ability to increase hepatocyte's sensitivity to this hormone, increasing expression and secretion of hepatic FGF21, which may reverse steatosis by inducing lipolysis. In addition, physical exercise is able to reduce miR149 and miR212 and, consequently, increase FGF21, which is also related to liver fat reduction. Therefore, noting the relevance of NAFLD, studies are necessary to understand the intrinsic and extrinsic mechanisms that promote the prevention or promotion for this disease development. Among the many possibilities, the current project intends to explore the relation of the glucagon-FGF21-miR149 and glucagon-FGF21-miR212 axes through FGF21 overexpression to promote increase glucagon sensitivity in HepG2 cell treated with palmitate fatty acid. As well as comparing these results with the treatment of HepG2 using trained animal serum, simulating in vitro, a situation of physical exercise. This project will contribute to understand the action of each stimulus in preventing the progression of NAFLD.