Alterations in mouse visceral adipose tissue mRNA expression of islet G-protein-coupled receptor ligands in obesity.

Abstract

Adipose tissue mass expansion in obesity leads to alterations in expression and secretion of adipokines, some of which may alter islet function by binding to G-protein-coupled receptors (GPCRs) expressed by islets. We have therefore quantified expression of mRNAs encoding islet GPCR ligands in visceral adipose tissue retrieved from lean and diet-induced obese mice to determine alterations in islet GPCR ligand mRNAs in obesity. Epididymal adipose tissue was retrieved from C57BL/6 mice that had been maintained on a control-fat diet (10% fat) or high-fat diet (60% fat) for 16 weeks and RT-qPCR was used to quantify mRNAs encoding ligands for islet GPCRs. Of the 155 genes that encode ligands for islet GPCRs, 45 and 40 were expressed in visceral adipose tissue retrieved from lean and obese mice respectively. The remaining mRNAs were either expressed at trace level (0.0001% to 0.001% relative to Actb expression) or absent (<0.0001%). Obesity was associated with significant alterations in GPCR ligand mRNA expression in visceral adipose tissue, some of which encode for peptides with established effects on islet function (e.g. neuropeptide Y), or for GPCR ligands that have not previously been investigated for their effects on islets (e.g. (C-C motif) ligand 4; Ccl4). Mouse visceral adipose tissue showed significant alterations in expression of mRNAs encoding islet GPCR ligands in obesity. Our data point to ligands of interest for future research on adipose-islet crosstalk via secreted ligands acting at islet GPCRs. Such research may identify islet GPCRs with therapeutic potential for T2D.