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Review
. 2025 Jul 24.
doi: 10.1007/s12265-025-10670-7. Online ahead of print.

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

Yumeng Jia  1 , Lei Wang  2
Affiliations
Review

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

Yumeng Jia et al. J Cardiovasc Transl Res. .

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.

Keywords: Cardiometabolic diseases; GPR91; Inflammation; Metabolic dysregulation; Myocardial hypertrophy; Succinate.

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Conflict of interest statement

Declarations. Ethical Approval: No human or animal studies were carried out by the authors for this article. Consent to Participate: This study does not involve human participants; therefore, consent to participate is not applicable. Consent for Publication: All authors have given consent for publication. Human Subjects/Informed Consent Sstatement: No human studies were carried out by the authors for this article. Animal Studies: No animal studies were carried out by the authors for this article. Conflict of interest: The authors have no conflicts of interest to declare.

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