From Mechanisms to Diseases: The Succinate-GPR91 Axis in Cardiometabolic Diseases.

Abstract

Cardiometabolic diseases (CMD) encompass a cluster of cardiovascular disorders primarily driven by metabolic dysregulation, such as obesity-associated cardiomyopathy, hypertensive heart disease, and diabetic cardiomyopathy. The pathogenesis of CMD is closely linked to chronic inflammation, myocardial hypertrophy, and mitochondrial energy metabolism dysfunction. Recently, the succinate-GPR91 pathway, a critical hub for metabolic regulation, has gained attention for its role in CMD. In addition to its function as an intermediate in the TCA cycle, succinate also exerts a range of pathophysiological effects by acting as a signaling molecule through the activation of its receptor, GPR91.Studies indicate that in metabolic disorders such as obesity, hypertension, diabetes,and atherosclerosis, abnormal activation of the succinate-GPR91 axis exacerbates inflammation, accelerates myocardial hypertrophy, and induces mitochondrial dysfunction, contributing to cardiovascular damage. Targeting the succinate-GPR91 pathway may offer novel CMD therapies. This article reviews succinate's role in inflammation, hypertrophy, mitochondrial dysfunction, and other diseases, offering insights for CMD research and treatment.