Mechanistic link between nonalcoholic fatty liver disease and cardiometabolic disorders

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low-grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue can lead to NAFLD related with insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is one of the phenotypes of insulin resistance or metabolic syndrome. Many researchers have discovered a close association between NAFLD and insulin resistance, and focused on the role of NAFLD in the development of type 2 diabetes. Further, substantial evidence has suggested the association between NAFLD and cardiovascular disease (CVD). In the current review, we provide a plausible mechanistic link between NAFLD and CVD and the potential of the former as a therapeutic target based on pathophysiology. We also discuss in detail about the role of insulin resistance, oxidative stress, low-grade inflammation, abnormal lipid metabolism, gut microbiota, changes of biomarkers, and genetic predisposition in the pathological linking between NAFLD and cardiometabolic disorders.

Keywords: Atherosclerosis; Cardiovascular disease; Gut microbiota; Inflammation; Insulin resistance; Non-alcoholic fatty liver disease; Oxidative stress.