Abstract
In pregnancies complicated by maternal obesity and gestational diabetes mellitus, there is strong evidence to suggest that the insulin signaling pathway in the placenta may be impaired. This may have potential effects on the programming of the metabolic health in the offspring; however, a direct link between the placental insulin signaling pathway and the offspring health remains unknown. Here, we aimed to understand whether specific placental loss of the insulin receptor (InsR) has a lasting effect on the offspring health in mice. Obesity and glucose homeostasis were assessed in the adult mouse offspring on a normal chow diet (NCD) followed by a high-fat diet (HFD) challenge. Compared to their littermate controls, InsR KOplacenta offspring were born with normal body weight and pancreatic β-cell mass. Adult InsR KOplacenta mice exhibited normal glucose homeostasis on an NCD. Interestingly, under a HFD challenge, adult male InsR KOplacenta offspring demonstrated lower body weight and a mildly improved glucose homeostasis associated with parity. Together, our data show that placenta-specific insulin receptor deletion does not adversely affect offspring glucose homeostasis during adulthood. Rather, there may potentially be a mild and transient protective effect in the mouse offspring of multiparous dams under the condition of a diet-induced obesogenic challenge.
Highlights
We show that a cre reporter transgene expressing the green fluorescence protein (GFP) is expressed in the placental trophoblast cells where the
IPITT was repeated at 18 weeks on a high-fat diet (HFD) to see if the improvement was sustained in the male insulin receptor (InsR) KOplacenta mice, but the results revealed no differences in insulin tolerance in the male or female mice at this time (Figure S5E,E’)
We explored the role of the placental insulin receptor in a normal mouse pregnancy using a preclinical model, and our results suggest that placental InsR
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The growing prevalence of obesity and diabetes in pregnant women and women of reproductive age have become major concerns in women’s health, with over 60% of women of reproductive age being obese or overweight and an increasing number of pregnancies complicated by gestational diabetes mellitus (GDM) [1–4]. Maternal obesity and diabetes during pregnancy are associated with short- and long-term adverse pregnancy complications for both the mother and the baby [5–10]. Exposure to maternal obesity or diabetes in utero is associated with an increased risk for child and adult obesity, type 2 diabetes (T2D), cardiovascular disease, and neurodevelopmental disorders in the offspring [7,11–15]
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