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 vs 57±2 and 49 ±1 g), hyperglycemic (112±8 and 115±12 vs 92±10 and 96±8 mg/dL), with higher plasma insulin and leptin concentrations compared to female and male ND-Offs. Compared to male controls, male HFD-Offs exhibited similar systolic function but impaired diastolic function as indicated by increased IVRT (22±1 vs. 17±1), 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 dysfunction as well as reductions in cardiac SIRT3, resting free Ca⁺² levels and mitochondrial biogenesis.

中文翻译：

---

父母肥胖对后代心脏 SIRT3 表达、线粒体效率和生命早期舒张功能影响的性别差异

先前的研究表明，父母肥胖可能会对后代的长期代谢健康产生不利影响。我们检验了父母（父亲+母亲）肥胖会在生命早期损害后代心脏功能的假设。在断奶后的 1-3 天内，喂食高脂肪饮食 (HFD-Offs) 的肥胖大鼠的后代和来自瘦大鼠的年龄匹配的后代 (ND-Offs) 接受超声心动图和心导管检查，以评估压力-容积关系。然后，消化心脏并使用分离的心肌细胞来确定收缩功能、钙瞬变、与钙信号传导相关的蛋白质和线粒体生物能量学。女性和男性 HFD-Offs 较重（72±2 和 61±4 对 57±2 和 49±1 g），高血糖（112±8 和 115±12 对 92±10 和 96±8 mg/dL），与女性和男性 ND-Offs 相比，血浆胰岛素和瘦素浓度更高。与男性对照相比，男性 HFD-Offs 表现出相似的收缩功能，但舒张功能受损，如 IVRT（22±1 对 17±1）、E/E' 比（29±2 对 23±1）和 Tau 增加所示（5.7±0.2 对 4.8±0.2）。舒张功能受损与静息游离钙减少有关²⁺水平和受磷蛋白表达、活化基质金属蛋白酶 2 增加和 SIRT3 蛋白表达、线粒体 ATP 储备和 ATP 相关呼吸作用降低。这些结果表明，来自肥胖父母的男性和女性 Offs 在生命早期（断奶后 1-3 天）有多种代谢异常，男性，但不是女性，Offs 有舒张功能障碍受损以及心脏 SIRT3 减少，静息游离 Ca ⁺²水平和线粒体生物发生。