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

Abstract

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.

Serum fatty acid profiles associated with metabolic risk in women with polycystic ovary syndrome

“…Leptin and adiponectin, which are adipokines secreted by adipocytes, have a profound influence on insulin sensitivity (39). Women with PCOS present with adipokine alterations, such as increased leptin levels and decreased adiponectin levels.…”

The Role of Adipokines in Inflammatory Mechanisms of Obesity

“…Vildagliptin, a DDP-4 inhibitor used in therapy for type 2 diabetes, has been shown to increase adiponectin levels, as well as to improve inflammatory biomarkers and LDL oxidation in obese diabetic patients [ 147 ]. Preparations of the thiazolidinedione family’s activators of PPARγ improved adiponectin levels while possessing a neutral effect on leptin levels in several studies including participants with NAFLD, nonalcoholic steatohepatitis, and type 2 diabetes; however, their clinical use was limited by long-term side effects such as increased risk of myocardial infarction [ 148 ]. Pioglitazone, a drug from the thiazolidinediones family, has been also shown to upregulate circulating omentin-1 levels [ 149 ].…”

Neuregulin 4 as a novel adipokine in energy metabolism

“…Modulating adipokines, which act as crosstalk messengers between adipose tissue and other organs, has recently provided new insights into the pathogenesis of metabolic diseases and may have treatment prospects ( Cheng and Yu, 2022 ; Francisco et al, 2022 ; Kim et al, 2022 ). In recent years, the role of Nrg4 as a novel signaling protein in metabolic derangements have been revealed and may serve as a novel therapeutic candidate.…”