Trigonelline Improves Metabolism and Cardiac Function of HFpEF Mice Via Gut Microbiome Alterations-Mediated AMPK Activation.

ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) is a prevalent end-manifestation of cardiovascular diseases currently lacking effective treatment. Using a high-fat diet and L-NAME-induced mouse model, untargeted metabolomic profiling is performed and trigonelline is identified as a markedly reduced metabolite in HFpEF hearts. Oral trigonelline supplementation alleviates metabolic syndromes, including obesity, insulin resistance, and hepatic injury, leading to improved cardiac function in HFpEF mice. AMPK inhibition blunts the protective effects of trigonelline despite trigonelline per se not activating AMPK directly. Gut microbiota is required in AMPK activation and consequent beneficial effects on HFpEF mice by trigonelline. Further investigations demonstrate that trigonelline sign

SUBMITTER: Cheng Z 

PROVIDER: S-EPMC12849935 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature