RT Journal Article
SR Electronic
T1 Maternal Obesity and Western-Style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 1389
OP 1400
DO 10.2337/db19-1218
VO 69
IS 7
A1 Campodonico-Burnett, William
A1 Hetrick, Byron
A1 Wesolowski, Stephanie R.
A1 Schenk, Simon
A1 Takahashi, Diana L.
A1 Dean, Tyler A.
A1 Sullivan, Elinor L.
A1 Kievit, Paul
A1 Gannon, Maureen
A1 Aagaard, Kjersti
A1 Friedman, Jacob E.
A1 McCurdy, Carrie E.
YR 2020
UL http://diabetes.diabetesjournals.org/content/69/7/1389.abstract
AB 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.