Leigang Jin, Leiluo Geng, Lei Ying, Lingling Shu, Kevin Ye, Ranyao Yang, Yan Liu, Yao Wang, Yin Cai, Xue Jiang, Qin Wang, Xingqun Yan, Boya Liao, Jie Liu, Fuyu Duan, Gary Sweeney, Connie Wai Hong Woo, Yu Wang, Zhengyuan Xia, Qizhou Lian, Aimin Xu
BACKGROUND: Exercise is an effective nonpharmacological strategy to alleviate diabetic cardiomyopathy (DCM) through poorly defined mechanisms. FGF21 (fibroblast growth factor 21), a peptide hormone with pleiotropic benefits on cardiometabolic homeostasis, has been identified as an exercise responsive factor. This study aims to investigate whether FGF21 signaling mediates the benefits of exercise on DCM, and if so, to elucidate the underlying mechanisms. METHODS: The global or hepatocyte-specific FGF21 knockout mice, cardiomyocyte-selective β-klotho (the obligatory co-receptor for FGF21) knockout mice, and their wild-type littermates were subjected to high-fat diet feeding and injection of streptozotocin to induce DCM, followed by a 6-week exercise intervention and assessment of cardiac functions...
September 22, 2022: Circulation