Causal Relationship of Non-alcoholic Fatty Liver Disease with Obesity and Insulin Resistance

Obesity has reached epidemic proportions in the world. Nonalcoholic fatty liver disease (NAFLD) affects around one-third of Western countries, with an incidence that continues to also increase in other parts of the world, especially in Asia. NAFLD is frequently associated with obesity, type 2 diabetes mellitus, and dyslipidemia. Epidemiologic studies show that obesity and insulin resistance are the most prevalent risk factors for NAFLD, and insulin resistance is an essential requirement for the development of NAFLD. Hyperinsulinemia directly promotes fat accumulation in hepatocytes. In addition, the pathogenesis of hepatic steatosis is complex, with visceral fat, adipokines, and inflammatory cytokines such as IL-6 and TNF-α all appearing to be involved to some extent. An alternative hypothesis is that excess triglycerides in the liver may cause insulin resistance. NAFLD can promote lipotoxicity and adipose tissue inflammation and can influence development of insulin resistance.Thus, insulin resistance should be taken into consideration to elucidate the pathogenesis of NAFLD.ope