These results demonstrate that in diabetic db/db mice, FGFR4 activation promotes pathological cardiac remodeling, including concentric hypertrophy and interstitial fibrosis, providing further evidence for a critical role for FGF21-FGFR4 signaling in the cardiomyopathy associated with T2D. This evidence concerns the gene FGFR4 and type 2 diabetes mellitus.