Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA.
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH, USA; Department of Surgery, Division of General and Gastrointestinal Surgery, The Ohio State University College of Medicine, Columbus, OH, USA.
Mol Metab. 2024 Apr;82:101914. doi: 10.1016/j.molmet.2024.101914. Epub 2024 Mar 11.
The intrauterine environment during pregnancy is a critical factor in the development of obesity, diabetes, and cardiovascular disease in offspring. Maternal exercise prevents the detrimental effects of a maternal high fat diet on the metabolic health in adult offspring, but the effects of maternal exercise on offspring cardiovascular health have not been thoroughly investigated.
To determine the effects of maternal exercise on offspring cardiovascular health, female mice were fed a chow (C; 21% kcal from fat) or high-fat (H; 60% kcal from fat) diet and further subdivided into sedentary (CS, HS) or wheel exercised (CW, HW) prior to pregnancy and throughout gestation. Offspring were maintained in a sedentary state and chow-fed throughout 52 weeks of age and subjected to serial echocardiography and cardiomyocyte isolation for functional and mechanistic studies.
High-fat fed sedentary dams (HS) produced female offspring with reduced ejection fraction (EF) compared to offspring from chow-fed dams (CS), but EF was preserved in offspring from high-fat fed exercised dams (HW) throughout 52 weeks of age. Cardiomyocytes from HW female offspring had increased kinetics, calcium cycling, and respiration compared to CS and HS offspring. HS offspring had increased oxidation of the RyR2 in cardiomyocytes coupled with increased baseline sarcomere length, resulting in RyR2 overactivity, which was negated in female HW offspring.
These data suggest a role for maternal exercise to protect against the detrimental effects of a maternal high-fat diet on female offspring cardiac health. Maternal exercise improved female offspring cardiomyocyte contraction, calcium cycling, respiration, RyR2 oxidation, and RyR2 activity. These data present an important, translatable role for maternal exercise to preserve cardiac health of female offspring and provide insight on mechanisms to prevent the transmission of cardiovascular diseases to subsequent generations.
妊娠期间的宫内环境是肥胖、糖尿病和心血管疾病在后代中发生的关键因素。母体运动可预防母体高脂肪饮食对成年后代代谢健康的有害影响，但母体运动对后代心血管健康的影响尚未得到彻底研究。
为了确定母体运动对后代心血管健康的影响，雌性小鼠在怀孕前和整个孕期分别喂食标准饮食（C；脂肪提供 21%的热量）或高脂肪饮食（H；脂肪提供 60%的热量），并进一步分为久坐不动（CS、HS）或轮式运动（CW、HW）。后代在 52 周龄前保持久坐不动和标准饮食，并进行连续超声心动图和心肌细胞分离，以进行功能和机制研究。
高脂肪饮食的久坐不动的母鼠（HS）所产的雌性后代与喂食标准饮食的母鼠（CS）所产的后代相比，射血分数（EF）降低，但在高脂肪饮食的运动母鼠（HW）所产的后代中，EF 在 52 周龄时一直保持。HW 雌性后代的心肌细胞具有更高的动力学、钙循环和呼吸作用，与 CS 和 HS 后代相比。HS 后代的 RyR2 在心肌细胞中的氧化增加，同时伴有基线肌节长度增加，导致 RyR2 过度活跃，HW 雌性后代的这种情况则被消除。
这些数据表明，母体运动可以保护雌性后代免受母体高脂肪饮食的有害影响，改善后代的心脏健康。母体运动提高了雌性后代心肌细胞的收缩、钙循环、呼吸、RyR2 氧化和 RyR2 活性。这些数据为母体运动保护雌性后代心脏健康提供了重要的、可转化的作用，并为预防心血管疾病向后代传播提供了机制上的见解。
