The role of adipocytokines in the development of non-alcoholic fatty liver disease in children and adolescents

Abstract

Over the past 20 years, the proportion of overweight and obese children and adolescents has increased significantly in most countries. Obesity represents a major cardiometabolic risk and is closely associated with comorbidities such as hypertension, hyperlipidemia, hyperinsulinemia, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). There is a lot of uncertainty regarding the diagnosis of metabolic syndrome in children, mainly due to the various and conflicting definitions that have been proposed. The prevalence of metabolic syndrome varied significantly in children (from 6 to 39%) depending on the applied definition criteria. According to these definitions, only 2% of children met all the criteria for metabolic syndrome. Over the past decade, studies have shown that, in parallel with the increase in the prevalence of obesity in the pediatric population, NAFLD has become the most common form of liver disease in childhood. In NAFLD, inflammatory cytokines/adipokines and other factors lead to steatohepatitis and/or fibrosis. Recently, several adipocytokines and inflammatory cytokines have been identified with significant positive (leptin, chemerin, vaspin, TNF-α, IL-6 and IL-8) or negative (adiponectin) associations with metabolic risk factors. Some of them can be considered as pathophysiological factors linking obesity and its complications such as insulin resistance and NAFLD. However, data on other adipocytokines and their role in metabolism remain controversial and partially unknown, especially with regard to their role in childhood (resistin, NAMPT, FGF-21, A-FABP, RBP4, lipocalin-2, omentin-1, hsCRP). Adipocytokines are a novel and powerful tool not only for the diagnosis and stratification of NAFLD and the metabolic syndrome, but also as a potential therapeutic target. Adipocytokine therapy requires further study in all patients with metabolic syndrome and NAFLD, especially in children and adolescents.