Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

Abstract

Simple SummaryNon-alcoholic fatty liver disease (NAFLD) is an unmet medical need due to its increasingly high incidence, severe clinical consequences, and the absence of feasible diagnostic tools and effective drugs. This review summarizes the preclinical and clinical data on adipokines, cytokine-like hormones secreted by adipose tissue, and NAFLD. The aim is to establish the potential of adipokines as diagnostic and prognostic biomarkers, as well as their potential as therapeutic targets for NAFLD. The limitations of current research are also discussed, and future perspectives are outlined.Non-alcoholic fatty liver disease (NAFLD) has become the major cause of chronic hepatic illness and the leading indication for liver transplantation in the future decades. NAFLD is also commonly associated with other high-incident non-communicable diseases, such as cardiovascular complications, type 2 diabetes, and chronic kidney disease. Aggravating the socio-economic impact of this complex pathology, routinely feasible diagnostic methodologies and effective drugs for NAFLD management are unavailable. The pathophysiology of NAFLD, recently defined as metabolic associated fatty liver disease (MAFLD), is correlated with abnormal adipose tissue–liver axis communication because obesity-associated white adipose tissue (WAT) inflammation and metabolic dysfunction prompt hepatic insulin resistance (IR), lipid accumulation (steatosis), non-alcoholic steatohepatitis (NASH), and fibrosis. Accumulating evidence links adipokines, cytokine-like hormones secreted by adipose tissue that have immunometabolic activity, with NAFLD pathogenesis and progression; however, much uncertainty still exists. Here, the current knowledge on the roles of leptin, adiponectin, ghrelin, resistin, retinol-binding protein 4 (RBP4), visfatin, chemerin, and adipocyte fatty-acid-binding protein (AFABP) in NAFLD, taken from preclinical to clinical studies, is overviewed. The effect of therapeutic interventions on adipokines’ circulating levels are also covered. Finally, future directions to address the potential of adipokines as therapeutic targets and disease biomarkers for NAFLD are discussed.