Irisin may be involved in exendin-4 mitochondrial action in human adipocytes

Introduction Disturbed mitochondrial activity in adipocytes is suggested as one of the mechanisms involved in metabolic dysfunction in obesity. Glucagon-like peptide receptor agonists (GLP-1RAs) are used to normalize glucose level and reduce body weight. GLP-1 activates similar intracellular pathway as irisin, peptide that modulate metabolism by stimulating the ‘browning’ of adipocytes. The aim of the study was to investigate the mechanisms of the GLP-1RA, exendin-4, action at the level of mRNA, proteins and mitochondrial activity in human adipocytes. Material and methods The human preadipocytes Chub-S7 were differentiated in vitro to mature adipocytes and then stimulated with exendin-4 at 100 nM for 24 h. Expression of mRNA and proteins (irisin, adiponectin, visfatin/NAMPT) were measured. Oxygen consumption rates and intracellular ATP content were determined. Results The exendin-4 enhanced the secretion of irisin and visfatin by adipocytes. The up-regulated expression of FNDC5, NAMPT and UCP2 genes was accompanied by modest changes in mitochondrial activity in exendin-4 treated adipocytes. Exendin-4 exerted similar effect on mitochondrial oxygen consumption rates as irisin, including increased maximum mitochondrial respiration and reserve capacity with unchanged intracellular ATP. Conclusions Increasing energy expenditure by exendin-4 may be associated with upregulation of irisin in human adipocytes. Clinical studies are necessary to confirm the hypothesis that nutrients, by stimulating the secretion of GLP-1, may influence the expression of irisin and thus modulate the mitochondrial metabolism of adipocytes.