Sex-Specific early cardiac dysfunction in Offsprings of C57BL/6J mice continuously exposed to High-Fat, High-Sucrose Diets

The objective of this study was to investigate the sex-specific cardiac effects of maternal and lifelong exposure to a high-fat, high-sucrose (HFHS) diet in offspring. We hypothesized that continuous HFHS diet exposure would induce sex-specific metabolic and cardiac dysfunctions. Dams were fed either a standard laboratory chow diet (CON) or an HFHS diet for 8 weeks before pregnancy and throughout gestation and lactation. Offspring remained on the same maternal diet (CON or HFHS) until tissue collection at 29–32 weeks of age. Body composition and glucose tolerance tests (GTT) were performed at 6 and 28 weeks of age. Pressure-volume loops were obtained at 29–32 weeks using the Transonic ADV 500 system to evaluate cardiac parameters. Continuous HFHS exposure significantly increased body weight and fat mass in male offspring compared to CON-fed males, with no effects observed in females. Relative heart weight normalized to tibia length was higher in males than females, regardless of diet. Female HFHS offspring developed glucose intolerance at 6 weeks, while males did not. P-V loop analysis revealed evidence of left ventricular (LV) systolic contractile dysfunction in male offspring exposed to an HFHS diet. End-systolic volume (ESV) was significantly higher in HFHS males compared to controls. Load-independent contractility, assessed after vena cava occlusion, showed that the slope of end-systolic elastance (Ees) was significantly reduced in HFHS males, while the ventricular-arterial coupling ratio (Ea/Ees) was significantly elevated, indicating impaired contractile efficiency. In contrast, females on HSHF diet showed signs of early diastolic dysfunction by significant decrease of end diastolic elastance (Eed). Signs of diastolic dysfunction were not present in males on HSHF diet. In summary, long-term exposure to an HFHS diet results in sex-specific metabolic and cardiac dysfunctions. Males exhibited increased body weight, fat mass, and significant systolic impairments, including reduced LV contractility and coupling efficiency. In contrast, females showed glucose intolerance at 6 weeks and evidence of an early diastolic dysfunction. This work was supported by the National Institute of Health [NIH, NIGMS, grant GM125603] to EC. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.