Adolescent high fructose consumption induces cardiac dysfunction in adulthood via elevated histone acetylation.

BACKGROUND: High fructose corn syrup (HFCS) has increasingly displaced sucrose throughout the world due to its lower cost. Importantly, there has been more fructose in HFCS, vis a vis glucose, than is considered safe, and generally-recognized-as-safe (GRAS). Fructose is linked to hypertension, lipid dysregulation and insulin resistance, all of which increase the risk for cardiovascular disease (CVD). This study aimed to evaluate the long-term effects of adolescent high fructose intake on adult cardiac function and elucidate the mechanisms. Most studies to date overemphasize the overconsumption of sugar, HFCS, and sugar-sweetened beverages (SSBs) in particular as the primary culprit, while placing insufficient emphasis on the inherently unsafe fructose-to-glucose ratio in HFCS. Moreover, a growing body of research has identified a close correlation between direct fructose exposure and the pathogenesis of various diseases. METHODS: Young mice were given high-fructose drinking (HFD) water from 3 to 8 weeks of age. Cardiac ultrasound and histochemical staining were performed to assess cardiac structure and pathology. Heart tissues and cells were collected for quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis to determine the mRNA levels of Anp, Bnp, β-MHC, Col1a1, Col3a1, Cpt1b, as well as histone acetylation status. RESULTS: Compared with controls, HFD mice exhibited ventricular dilation, impaired cardiac function, cardiomyocyte hypertrophy, and increased myocardial fibrosis. In the high-fructose group, Bnp and β-MHC mRNA expression was upregulated, whereas Cpt1b expression was reduced. Mechanistically, histone acetylation levels were elevated in the high-fructose group, accompanied by decreased SIRT1 protein expression in heart tissues-a key indicator of aging related heart changes and CVD. CONCLUSIONS: Adolescent high fructose intake impairs adult cardiac function by downregulating Cpt1b and increasing histone acetylation, suggesting novel mechanisms and therapeutic targets for fructose-induced cardiac dysfunction.