Maternal Obesity and Western-Style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates
Open Access
- 30 April 2020
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 69 (7), 1389-1400
- https://doi.org/10.2337/db19-1218
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 Japanese macaque model to investigate whether maternal obesity combined with a Western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed a control or WSD prior to and during pregnancy through lactation, and offspring subsequently weaned to a control or WSD. Muscle glucose uptake and signaling were measured ex vivo in fetal (n = 5–8/group) and juvenile (n = 8/group) offspring. In vivo signaling was evaluated after an insulin bolus just prior to weaning (n = 4–5/group). Maternal WSD reduced insulin-stimulated glucose uptake and impaired insulin signaling at the level of Akt phosphorylation in fetal muscle. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and postweaning WSD and corresponded to modest reductions in insulin-stimulated Akt phosphorylation relative to controls. We conclude that maternal WSD leads to a persistent decrease in offspring muscle insulin-stimulated glucose uptake even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not reverse the effects of maternal WSD on muscle insulin action, suggesting earlier interventions may be warranted.Keywords
Funding Information
- National Institute of Child Health and Human Development (K12 HD057022)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24 DK090964, R01 DK089201)
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