Previous studies suggest that parental obesity may adversely impact long-term metabolic health of the offspring. We tested the hypothesis that parental (paternal + maternal) obesity impairs cardiac function in the offspring early in life. Within 1-3 days after weaning, offspring from obese rats fed a high-fat diet (HFD-Offs) and age-matched offspring from lean rats (ND-Offs) were submitted to echocardiography and cardiac catheterization for assessment of pressure-volume relationships. Then, hearts were digested and isolated cardiomyocytes were used to determine contractile function, calcium transients, proteins related to calcium signaling, and mitochondrial bioenergetics. Female and male HFD-Offs were heavier (72 ± 2 and 61 ± 4 g vs. 57 ± 2 and 49 ± 1 g), hyperglycemic (112 ± 8 and 115 ± 12 mg/dL vs. 92 ± 10 and 96 ± 8 mg/dL) with higher plasma insulin and leptin concentrations compared with female and male ND-Offs. When compared with male controls, male HFD-Offs exhibited similar systolic function but impaired diastolic function as indicated by increased IVRT (22 ± 1 vs. 17 ± 1 ms), E/E' ratio (29 ± 2 vs. 23 ± 1), and tau (5.7 ± 0.2 vs. 4.8 ± 0.2). The impaired diastolic function was associated with reduced resting free Ca2+ levels and phospholamban protein expression, increased activated matrix metalloproteinase 2, and reduced SIRT3 protein expression, mitochondrial ATP reserve, and ATP-linked respiration. These results indicate that male and female Offs from obese parents have multiple metabolic abnormalities early in life (1-3 days after weaning) and that male, but not female, Offs have impaired diastolic function as well as reductions in cardiac SIRT3, resting free Ca2+ levels, and mitochondrial biogenesis.NEW & NOTEWORTHY Parental obesity contributes to diastolic dysfunction in young offspring (1-3 days after weaning) in a sex-dependent manner, as well as reduced cardiac SIRT3 expression and altered mitochondrial bioenergetics, resting Ca2+ levels, and reduced phospholamban protein levels.
Keywords: diastolic function; heart; mitochondrial function; sirtuins; systolic function.