Hemp seed fiber supplementation alleviates myocardial hypertrophy in aging mice through activation of mitophagy

Aging-induced cardiac hypertrophy is a key risk factor for cardiovascular disease (CVD). The gut-heart axis, gut microbiota, and their metabolite short-chain fatty acids (SCFAs)—which regulate cardiac function—have attracted significant attention. Hemp seeds are rich in dietary fiber, which can be fermented by gut microbiota to produce SCFAs. However, whether hemp seed fiber alleviates cardiac hypertrophy in aging mice by improving gut microbiota composition and increasing SCFA levels remains unclear. Male C57BL/6 mice were divided into 5 groups: adult control group (5-month-old, standard diet), old control group (18-month-old, standard diet), and three old mice groups supplemented with low, medium, and high-dose hemp seed fiber group, with a 12-week intervention. Cardiac hypertrophy (thicker ventricular walls, larger cardiomyocyte cross-sectional area) was observed in old mice. Hemp seed fiber significantly improved this phenotype, reduced hypertrophy markers (myh7, bnp), increased SCFA-related microbiota abundance, and elevated serum SCFAs. The mechanism may involve upregulating GPR41, inhibiting excessive Akt phosphorylation, and promoting mitophagy. • Hemp seed fiber significantly alleviates myocardial hypertrophy in old mice, reducing indices such as left ventricular wall thickness and the mRNA expression of hypertrophy markers. • Hemp seed fiber increases the abundance of SCFA-producing gut microbiota and elevates the serum levels of acetate, propionate, and butyrate in old mice. • Hemp seed fiber initiates PINK1/Parkin/P62-mediated mitophagy and reduces myocardial apoptosis by activating cardiac GPR41 receptors and inhibiting excessive Akt phosphorylation. • This study reveals that hemp seed fiber ameliorates age-related myocardial hypertrophy through a novel gut-heart axis-related pathway, providing a scientific basis for dietary intervention.