Emerging Molecular Targets for Treatment of Nonalcoholic Fatty Liver Disease

NALFD is becoming a global epidemic with serious hepatic and extrahepatic complications, but no approved therapeutic drugs are available. Lipid metabolic perturbation and metabolic-stress-induced inflammation form the core of the pathogenesis of NAFLD. Innate immune signaling is a key regulator in metabolic inflammation, acting as a driving force in NAFLD progression. Several therapeutic targets regulating the lipid metabolism and innate immunity of NAFLD have been identified and have shown promising results in clinical trials. Systems-based multiomic analyses and big data technology, combined with advances in disease models, will be useful for discovering potential therapeutic targets, accelerating the translation from basic to clinic, and providing individualized therapy. In parallel with the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide. Disequilibrium of lipid metabolism and the subsequent metabolic-stress-induced inflammation are believed to be central in the pathogenesis of NAFLD. Of note, metabolic inflammation is primarily mediated by innate immune signaling, which is increasingly recognized as a driving force in NAFLD progression. Currently, a series of agents targeting one or more of these pathomechanisms have shown encouraging results in preclinical models and clinical trials. This review summarizes the emerging molecular targets involved in signaling in the lipid metabolism and innate immunity aspects of NAFLD, focusing on their mechanistic roles and translational potentials. In parallel with the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide. Disequilibrium of lipid metabolism and the subsequent metabolic-stress-induced inflammation are believed to be central in the pathogenesis of NAFLD. Of note, metabolic inflammation is primarily mediated by innate immune signaling, which is increasingly recognized as a driving force in NAFLD progression. Currently, a series of agents targeting one or more of these pathomechanisms have shown encouraging results in preclinical models and clinical trials. This review summarizes the emerging molecular targets involved in signaling in the lipid metabolism and innate immunity aspects of NAFLD, focusing on their mechanistic roles and translational potentials.