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 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.

Maternal Exercise Improves High-Fat Diet-Induced Metabolic Abnormalities and Gut Microbiota Profiles in Mouse Dams and Offspring

“…The adverse nutritional environment in early life might be one of the important factors in deciphering the rapid development of obesity and metabolic disorders. During the last decade, growing numbers of animal experimental models have demonstrated that maternal obesity or HFD resulted in increased offspring susceptibility to metabolic disorders (Campodonico-Burnett et al, 2020;Costa et al, 2020). Concordantly, our study also demonstrated that maternal HFD not only led to glucose and lipid metabolic disturbances in dams but also programmed glucose intolerance and disorders of serum lipid profiles in male offspring from young into adulthood.…”

Developmental programming of peripheral diseases in offspring exposed to maternal obesity during pregnancy

“…In animal studies, the effects of a control or low-fat post-weaning diet have been investigated. For example, in rats, consumption of a control diet postweaning did not reverse the metabolic phenotype caused by exposure to an obesogenic diet in utero (12), nor did a control postweaning diet restore cardiovascular function in males (70). This suggests that any adverse outcomes of the in utero environment cannot be negated by the postweaning diet.…”

Fetal programming of human energy homeostasis brain networks: Issues and considerations

“…Indeed, a rapidly growing and convergent body of epidemiological, clinical, and experimental evidence in humans and animals suggests that the origins of obesity can be traced, in part, back to developmental processes occurring during the intrauterine period of life, at which time the developing embryo/fetus responds to “suboptimal” conditions by producing structural and functional changes in cells, tissues, and organ systems that persist across the life span and modulate susceptibility for many complex common disorders (i.e., the concept of fetal, or developmental, programming of health and disease risk). To date, research on fetal programming of obesity has focused largely on processes and mechanisms within peripheral cells, tissues, and organ systems, such as adipocyte, 17 pancreas, 18 liver, 19–21 and muscle 22,23 biology. Although this focus is entirely justified, we suggest there is yet another system of critical importance that also warrants attention in the context of fetal programming: the brain circuitry that underlies energy balance homeostasis.…”