Succinate-GPR91 signaling promotes cardiomyocyte metabolic reprogramming and NAD⁺ production to alleviate HFpEF.

ABSTRACT:

Background

Disrupted cardiomyocyte energy metabolism is a hallmark of heart failure with preserved ejection fraction (HFpEF). Succinate, a key intermediate of the tricarboxylic acid cycle, is markedly decreased in HFpEF myocardium. In addition to its metabolic role, succinate functions as a signaling molecule that activates GPR91 to regulate metabolic and immune pathways. However, the precise contributions and mechanisms of cardiomyocyte succinate-GPR91 signaling in HFpEF pathogenesis remain incompletely understood.

Methods

HFpEF models were established in wild-type (WT), global GPR91 knockout (Gpr91^-/-), and cardiomyocyte-specific GPR91 knockout (Gpr91^ΔCM) mice, with or without succinate supplementation. Cardiac structure, function, and metabolic pheno

SUBMITTER: Jia Y 

PROVIDER: S-EPMC12781658 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature