Maternal exercise intervention in obese pregnancy improves the cardiovascular health of the adult male offspring

Abstract

ObjectiveObesity 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.MethodsA 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.ResultsAt 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.ConclusionsExercise 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.

Exercise during pregnancy mitigates the adverse effects of maternal obesity on adult male offspring vascular function and alters one‐carbon metabolism

“…To our knowledge, no studies have reported on whether exercise during pregnancy can mitigate the adverse effects of maternal obesity on offspring vascular endothelial function. A recent study reported that maternal treadmill training can mitigate the adverse effects of maternal obesity on cardiac function in adult male C57BL/6J mouse offspring; vascular function was not assessed (Beeson et al, 2018). Taken together with our findings, exercise during pregnancy may be an effective nonpharmacological intervention to prevent adverse cardiovascular outcomes in offspring from mothers with gestational obesity.…”

Exercise alters the molecular pathways of insulin signaling and lipid handling in maternal tissues of obese pregnant mice

“…In line with the observed increased overall adiposity in both obese sedentary and exercised mice (Fernandez‐Twinn et al ; Beeson et al ), WAT mass expansion and fat deposition in liver, skeletal muscle and WAT was not significantly different in these two obese groups. This observation was also consistent with the maternal hyperleptinemia of both obese groups during pregnancy shown previously (Fernandez‐Twinn et al ).…”

“…The molecular changes induced by obesity alone and in response to exercising the obese dams were tissue specific and, in some instances, were related to alterations in maternal biochemical composition and concentrations of specific hormones and metabolites in late pregnancy. There were no beneficial effects of maternal exercise on the fetal growth restriction induced by maternal obesity despite the long term beneficial effects of the current exercise intervention in obese dams on cardiac (Beeson et al ) and metabolic health (Fernandez‐Twinn et al ) in adult offspring. Importantly this suggests that it is not fetal growth restriction per se that may mediate the long‐term detrimental health consequences of maternal obesity on the offspring (Fernandez‐Twinn et al ; Beeson et al ).…”

“…There were no beneficial effects of maternal exercise on the fetal growth restriction induced by maternal obesity despite the long term beneficial effects of the current exercise intervention in obese dams on cardiac (Beeson et al ) and metabolic health (Fernandez‐Twinn et al ) in adult offspring. Importantly this suggests that it is not fetal growth restriction per se that may mediate the long‐term detrimental health consequences of maternal obesity on the offspring (Fernandez‐Twinn et al ; Beeson et al ). Taken together, our data highlight the specific physiological and molecular mechanisms operating during pregnancy that mediate the beneficial effects of exercise on maternal and offspring outcomes in obese pregnancies.…”

“…In mice, exercise also ameliorates the increased levels of maternal oxidative stress (Vega et al ) and placental hypoxia and lipid accumulation associated with maternal obesity (Fernandez‐Twinn et al ). Furthermore, there is accumulating evidence that maternal exercise has beneficial effects on cardiometabolic outcomes of the offspring in overweight or obese women (Barakat et al ; Patel et al ) and in experimental animals (Carter et al ; Carter et al ; Rajia et al ; Laker et al ; Blaize et al ; Raipuria et al ; Vega et al ; Stanford et al ; Fernandez‐Twinn et al ; Quiclet et al ; Ribeiro et al ; Stanford et al ; Beeson et al ; Cunningham et al ). However, the physiological and molecular impact of exercise on the metabolically active tissues of the mother, which may lead to improved pregnancy outcomes, remain unknown.…”