Metabolic Inflammation—A Role for Hepatic Inflammatory Pathways as Drivers of Comorbidities in Nonalcoholic Fatty Liver Disease?

Non-alcoholic fatty liver disease (NAFLD) is a global and growing health concern. Emerging evidence points towards metabolic inflammation as a key process in the fatty liver that contributes to multiorgan morbidity. Key extrahepatic comorbidities that are influenced by NAFLD are type 2 diabetes, cardiovascular disease and impaired neurocognitive function. Importantly, the presence of non-alcoholic steatohepatitis (NASH) and advanced hepatic fibrosis increase the risk for systemic comorbidity in NAFLD. Although the precise nature of the crosstalk between the liver and other organs has not yet been fully elucidated, there is emerging evidence that metabolic inflammation - in part emanating from the fatty liver - is the engine that drives cellular dysfunction, cell death and deleterious remodelling within various body tissues. This review describes several inflammatory pathways and mediators that have been implicated as links between NAFLD and type 2 diabetes, cardiovascular disease and neurocognitive decline.