Maternal Obesity and Western-style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates

Abstract

Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a nonhuman primate model to investigate whether maternal obesity combined with a western-style diet (WSD) impairs offspring muscle insulin action. Briefly, adult females were fed a control (CON) or WSD prior to and during pregnancy and lactation. Offspring were weaned to a CON or WSD. Muscle glucose uptake and insulin signaling were measured ex vivo in fetal and juvenile offspring. In vivo signaling was evaluated before and after an intravenous insulin bolus just prior to weaning. We find that fetal muscle exposed to maternal WSD had reduced insulin-stimulated glucose uptake and impaired insulin signaling. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and post-weaning WSD. Analysis of insulin signaling activation revealed distinct changes between fetal and post-weaning WSD exposure. We conclude that maternal WSD leads to a persistent decrease in insulin-stimulated glucose uptake in juvenile offspring even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not ameliorate the effects of maternal WSD suggesting earlier interventions may be necessary.