PT - JOURNAL ARTICLE AU - Long Li AU - Caoxin Huang AU - Hongyan Yin AU - Xiaofang Zhang AU - Dongmei Wang AU - Chen Ma AU - Jia Li AU - Yan Zhao AU - Xuejun Li TI - Interleukin-6 mediated exercise-induced alleviation of adiposity and hepatic steatosis in mice AID - 10.1136/bmjdrc-2020-001431 DP - 2021 Apr 01 TA - BMJ Open Diabetes Research & Care PG - e001431 VI - 9 IP - 1 4099 - http://drc.bmj.com/content/9/1/e001431.short 4100 - http://drc.bmj.com/content/9/1/e001431.full SO - BMJ Open Diab Res Care2021 Apr 01; 9 AB - Introduction Exercise training has been shown to be the most effective strategy to combat obesity and non-alcoholic fatty liver disease. However, exercise promotes loss of adipose tissue mass and improves obesity-related hepatic steatosis through mechanisms that remain obscure.Research design and methods To study the role of interleukin-6 (IL-6) in high-fat diet (HFD)-induced adiposity and hepatic steatosis during treadmill running, IL-6 knockout (IL-6 KO) mice and wild-type (WT) mice were randomly divided into lean, obese (fed a HFD) and trained obese groups (fed a HFD and exercise trained).Results After 20 weeks of HFD feeding and 8 weeks of treadmill running, we found that exercise obviously reduced HFD-induced body weight gain, inhibited visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) expansion and almost completely reversed obesity-related intrahepatic fat accumulation in WT mice. However, IL-6 knockout (IL-6 KO) mice are refractory to the benefits of treadmill training on body weight, VAT and SAT mass elevation, and hepatic steatosis. Moreover, a panel of lipolytic-related and thermogenic-related genes, including ATGL, HSL and PGC-1α, was upregulated in the VAT and SAT of WT mice that received exercise training compared with untrained mice, which was not observed in IL-6 KO mice. In addition, exercise training resulted in a significant inhibition of hepatic peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in WT mice, and these effects were not noted in IL-6 KO mice.Conclusion These results revealed that IL-6 is involved in the prevention of obesity and hepatic fat accumulation during exercise training. The mechanisms underlying these antiobesity effects may be associated with enhanced lipolysis and thermogenesis in white adipose tissue. The improvement in hepatic steatosis by exercise training may benefit from the marked inhibition of PPAR-γ expression by IL-6.All data relevant to the study are included in the article or uploaded as supplemental information.