Dysregulated succinate–GPR91 signaling has been implicated in obesity[18–22], hypertension[23, 24], diabetes, atherosclerosis, myocardial ischemia, arterial fibrillation, cardiac hypertrophy, metabolic dysfunction-associated steatohepatitis, non-alcoholic fatty liver disease, chronic neuroinflammation, rheumatoid arthritis et al. by regulating mitochondrial metabolism, inflammation, and fibrosis etal.[25–28] However, the precise role and molecular mechanisms of the succinate–GPR91 axis in HFpEF remain elusive. Here, SUCNR1 is linked to obesity due to melanocortin 4 receptor deficiency.