Exercise rescues obese mothers’ insulin sensitivity, placental hypoxia and male offspring insulin sensitivity

Abstract

The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.

High‐fat diet intake modulates maternal intestinal adaptations to pregnancy and results in placental hypoxia, as well as altered fetal gut barrier proteins and immune markers

“…Increases in circulating inflammatory factors as a result of maternal HFD intake result in placental hypoxia (Fernandez-Twinn et al 2017), which impacts placental vascularization (Hayes et al 2012;Li et al 2013), potentially by altering macrophage activation (Zhao et al 2018). Consistent with these observations, we found increased immunostaining of carbonic anhydrase IX, a placental hypoxia marker, in male (P < 0.0001) and female (P < 0.0001) placentas derived from HFD fed dams (Fig.…”

“…Increases in circulating inflammatory factors as a result of maternal HFD intake result in placental hypoxia (Fernandez‐Twinn et al . ), which impacts placental vascularization (Hayes et al . ; Li et al .…”

Effects of maternal lifestyle interventions on child neurobehavioral development: Follow‐up of randomized controlled trials

“…Conversely, other studies of prenatal lifestyle interventions showed no intervention effects on child anthropometrics or other early life metabolic risk factors (Ronnberg, Hanson & Nilsson, ; Tanvig, Vinter, Jorgensen et al ., ). Animal experiments do show that exercise interventions (Fernandez‐Twinn et al ., ; Moser, McDaniel, Woolard, Phillips, Franklin & Gordon, ; Vega, Reyes‐Castro, Bautista, Larrea, Nathanielsz & Zambrano, ) and dietary interventions (Zambrano, Martinez‐Samayoa, Rodriguez‐Gonzalez & Nathanielsz, ) during pregnancy in obese animals can prevent adverse physical health outcomes (Fernandez‐Twinn et al ., ; Vega et al ., ; Zambrano et al ., ) and learning abilities (Moser et al ., ) in the offspring, without affecting offspring memory performance (Moser et al ., ) and social behavior (Moser et al ., ). To the best of our knowledge other measures of neurobehavioral development has not been assessed in animal experiments yet.…”

“…Improving these biological mechanisms in turn are expected to improve child development (Van Lieshout & Krzeczkowski, ). Therefore, improving the lifestyle of obese women before and during pregnancy may be of great importance to reduce the potential negative impact of maternal obesity on child development (Alvarez‐Bueno, Cavero‐Redondo, Sanchez‐Lopez, et al ., ; Fernandez‐Twinn, Gascoin, Musial et al ., ; Van Lieshout & Krzeczkowski, ). Indeed, a recent study showed that a lifestyle intervention during pregnancy in obese women was effective in reducing infant adiposity (Patel, Godfrey, Pasupathy et al ., ), but until now no studies have investigated whether maternal lifestyle interventions have beneficial effects on children's neurobehavioral development.…”

Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta‐analysis of animal studies

“…53 Whether interventions aimed at reducing obesity in women of childbearing age could improve maternal and child's health needs to be investigated further. Some animal experiments provide evidence that exercise or dietary interventions during pregnancy could reverse the detrimental effects of maternal obesity on the offspring, [83][84][85][86][87] with potential sex differences. 85,87 In humans however, only a limited amount of studies examined the consequences of reducing maternal obesity on offspring health.…”