Visceral fat: A key mediator of NAFLD development and progression

Non-alcoholic fatty liver disease (NAFLD) has become a major public health concern affecting a quarter of the world's population. It encompasses a wide spectrum of liver pathologies from simple steatosis to steatohepatitis and fibrosis triggered by multiple risk factors. Besides overnutrition and obesity, recently a lot of attention has been focused on the role of visceral fat in development and progression of NAFLD and non-alcoholic steatohepatitis (NASH). Clinical and epidemiological studies suggest a direct correlation between liver fat content and abdominal fat which is mostly accounted for by the visceral fat. Free flow of fatty acids, bioactive and inflammatory molecules such as cytokines, and adipokines from visceral fat expose the liver to fat accumulation and inflammation. The constant release of pro-inflammatory factors and high-fat content in the circulation results in systemic inflammation and insulin resistance (IR). The metabolic consequences of IR result in hyperglycemia, dyslipidemia, elevated inflammatory markers and visceral adiposity, and this vicious cycle of visceral fat and IR induction further aggravates the fatty infiltration of hepatocytes. Also, high-fat content in hepatocytes modulates the mTOR signaling pathway further enhancing insulin secretion secondary to insulin resistance, lipid biosynthesis, and adipose expansion. This review expounds the pivotal role played by the visceral fat in inflammation, IR, and altered mTOR pathway leading to initiation and progression of NAFLD.