Role of Innate Immune Signaling in Non-Alcoholic Fatty Liver Disease

NALFD is becoming a global epidemic with severe complications, but few if any pharmacological therapies are available. Owing to its unique anatomy, microarchitecture, and cellular composition, the liver functions as an immune organ in addition to its roles in metabolism and detoxification. Innate immune signaling controls both inflammatory and metabolic profiles in the liver, and has potential to provide novel therapeutic targets in non-alcoholic steatohepatitis (NASH). Innate immune components mediate both canonical inflammation cascades and noncanonical metabolism-related pathways by modulating post-translational modifications or transcriptional coregulation, thus controlling NASH progression. Multi-omic analyses, cell signaling, and tissue-specific gene-editing technologies, combined with advances in disease models, will facilitate in-depth understanding of NAFLD and the discovery of new drugs. Non-alcoholic fatty liver disease (NAFLD) has become the most epidemic liver disease worldwide owing to rapid changes in lifestyle over the past few decades. This chronic condition intertwines with low-grade inflammation and metabolic disequilibrium, and potentiates the onset and progression of devastating hepatic and extrahepatic complications. In addition to an integral role in promoting host defense, recent studies also implicate innate immune signaling in a multitude of processes that control the progression of NAFLD. The focus of this review is to highlight emerging evidence regarding the role of innate immunity in NAFLD and the integration of different pathways that affect both inflammation and metabolism across the spectrum of this liver morbidity. Non-alcoholic fatty liver disease (NAFLD) has become the most epidemic liver disease worldwide owing to rapid changes in lifestyle over the past few decades. This chronic condition intertwines with low-grade inflammation and metabolic disequilibrium, and potentiates the onset and progression of devastating hepatic and extrahepatic complications. In addition to an integral role in promoting host defense, recent studies also implicate innate immune signaling in a multitude of processes that control the progression of NAFLD. The focus of this review is to highlight emerging evidence regarding the role of innate immunity in NAFLD and the integration of different pathways that affect both inflammation and metabolism across the spectrum of this liver morbidity.