Skeletal muscle interleukin‐6 regulates metabolic factors in iWAT during HFD and exercise training

OBJECTIVE: To investigate the role of skeletal muscle (SkM) interleukin (IL)‐6 in the regulation of adipose tissue metabolism. METHODS: Muscle‐specific IL‐6 knockout (IL‐6 MKO) and IL‐6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high‐fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks. RESULTS: Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL‐6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5′AMP activated protein kinase (AMPK)(Thr172) phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL‐6 MKO than Floxed mice on Chow. In addition, iWAT AMPK(Thr172) and hormone‐sensitive lipase (HSL)(Ser565) phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL‐6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH‐E1α) protein content was higher (P < 0.05) in HFD ExTr IL‐6 MKO than HFD ExTr Floxed mice. CONCLUSIONS: These findings indicate that SkM IL‐6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors.