University of Cambridge, Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Level 4, Box 289, Hills Road, Cambridge, CB2 0QQ, UK.
University of Cambridge, Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Level 4, Box 289, Hills Road, Cambridge, CB2 0QQ, UK; Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and NIHR Cambridge Comprehensive Biomedical Research Centre, Box 223, Cambridge, CB2 0SW, UK.
Mol Metab. 2018 Oct;16:35-44. doi: 10.1016/j.molmet.2018.06.009. Epub 2018 Jun 18.
Obesity during pregnancy is associated with an elevated risk of cardiovascular disease in the offspring. With increased numbers of women entering pregnancy overweight or obese, there is a requirement for targeted interventions to reduce disease risk in future generations. Using an established murine model of maternal obesity during pregnancy, we investigated if a treadmill exercise intervention in the mother could improve offspring cardiac health and explored potential underlying mechanisms.
A 20-minute treadmill exercise intervention protocol was performed 5 days a week in diet-induced obese female C57BL/6 mice 1 week prior to, and up to E17 of pregnancy. All male offspring were weaned onto a control diet and studied at 8 weeks of age when their cardiovascular physiology was assessed by in vivo echocardiography and non-invasive tail cuff plethysmography. Cardiomyocyte cell area, re-expression of fetal genes and the expression of calcium handling and sympathetic activation proteins were determined.
At 8 weeks, there was no difference in bodyweight or fat mass between groups. Offspring of obese dams developed pathologic cardiac hypertrophy, hypertension and cardiac dysfunction characterized by reduced ejection fraction (p < 0.001). Maternal exercise prevented cardiac hypertrophy and dysfunction but failed to prevent hypertension. These offspring of exercised dams also had enhanced (p < 0.001) levels of calcium handling proteins and a sympathetic-activated inotropic response.
Exercise in obese pregnancy was beneficial to offspring cardiac function and structure but did not influence hypertension suggesting they are programmed by separate mechanistic pathways. These data suggest combination interventions in obese pregnancies will be required to improve all aspects of the cardiovascular health of the next generation.
孕期肥胖与后代心血管疾病风险升高相关。随着越来越多的超重或肥胖女性进入孕期,需要采取有针对性的干预措施来降低后代的疾病风险。本研究通过建立孕期肥胖的小鼠模型,探讨母亲进行跑步机运动干预是否能改善后代的心脏健康,并探索潜在的机制。
在饮食诱导肥胖的 C57BL/6 雌性小鼠怀孕前 1 周开始,每周 5 天进行 20 分钟的跑步机运动干预。所有雄性后代均在断奶后(8 周龄)接受控制饮食,并通过体内超声心动图和非侵入性尾套血压测量评估其心血管生理学。测定心肌细胞面积、胎儿基因的再表达以及钙处理和交感神经激活蛋白的表达。
8 周龄时,各组间体重或脂肪量无差异。肥胖母鼠的后代发生病理性心肌肥厚、高血压和心功能障碍,表现为射血分数降低(p<0.001)。母鼠运动可预防心肌肥厚和心功能障碍,但不能预防高血压。运动母鼠的这些后代还具有增强的(p<0.001)钙处理蛋白水平和交感神经激活的变力反应。
肥胖孕期运动对后代心脏功能和结构有益,但对高血压没有影响,这表明它们是通过不同的机制途径编程的。这些数据表明,需要对肥胖孕妇进行联合干预,以改善下一代的心血管健康的所有方面。