<b>Maternal Obesity Programs Glucose Intolerance in Pregnant Female Offspring</b>

<p dir="ltr">Maternal obesity is a known risk factor for metabolic dysfunction in offspring, yet its impact on the pregnancy metabolism of female offspring remains unclear. This study investigated how maternal obesity, induced by high-fat (HF) feeding in C57BL/6J mice, affects the metabolic adaptation to pregnancy in female offspring. Dams were fed an HF diet (60% fat) or chow for three months before and during pregnancy. Offspring from HF-fed dams (OF-HFD) exhibited reduced fetal growth, followed by rapid postnatal catch-up and increased adult adiposity compared to offspring from chow-fed dams (OF-CD), despite having similar baseline glucose and insulin levels. During their pregnancies, OF-HFD exhibited blunted increases in maternal body fat, blood triglycerides, and insulin concentrations, accompanied by glucose intolerance. In cultured islets, glucose-stimulated insulin secretion was markedly reduced in pregnant OF-HFD, despite unchanged β-cell mass or proliferation. Hepatic triglyceride secretion decreased, while liver insulin signaling was enhanced, suggesting alterations in lipid and glucose metabolism. Feeding OF-HFD an HF diet before and during pregnancy further impaired fetal growth. These findings indicate that maternal obesity impairs the metabolic adaptation to pregnancy in female offspring, characterized by insulin insufficiency and disrupted lipid homeostasis. This may initiate a transgenerational cycle of metabolic dysfunction, potentially increasing the risk of gestational diabetes in subsequent generations. Our findings underscore the need for more research to explore these mechanisms in humans and to develop strategies to reduce the long-term impacts of maternal obesity.</p>