IL‐6 Indirectly Modulates The Induction Of Glyceroneogenic Enzymes In Adipose Tissue During Exercise

Abstract

Glyceroneogenesis is an important step in the control of fatty acid re‐esterification with PEPCK and PDK4 being key enzymes in this process. It has been suggested that IL‐6 regulates adipose tissue metabolism and gene expression during exercise. The purpose of this investigation was to determine the role of IL‐6 in modulating the effects of exercise on the expression of glyceroneogenic enzymes in mouse adipose tissue. To achieve these goals, we utilized IL‐6 ex vivo treatment in cultured adipose tissue in combination with IL‐6−/−mice model. Treatment of cultured epididymal adipose tissue (eWAT), increased the phosphorylation of AMPK, ACC and STAT3 and induced SOCS3 mRNA levels while decreasing PEPCK mRNA. The activation of AMPK was independent of increases in lipolysis. An acute bout of treadmill running did not result in the induction of SOCS3 or increases in the phosphorylation of STAT3 in eWAT from WT mice. Exercise‐induced increases in PEPCK and PDK4 mRNA expression were attenuated in eWAT from IL‐6−/− mice in parallel with a greater relative increase in AMPK phosphorylation compared to exercised WT mice. These changes occurred independent of alterations in beta‐adrenergic signalling in adipose tissue from IL‐6−/− mice. Our findings question the role of IL‐6 signalling in adipose tissue during exercise and demonstrate an indirect effect of this cytokine in the regulation of adipose tissue gene expression.This work was supported by a Bridge Funding Operating Grant from the Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes to David C. Wright.