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Maternal obesity-induced endoplasmic reticulum stress causes metabolic alterations and abnormal hypothalamic development in the offspring

Abstract : The steady increase in the prevalence of obesity and associated type II diabetes mellitus is a major health concern, particularly among children. Maternal obesity represents a risk factor that contributes to metabolic perturbations in the offspring. Endoplasmic reticulum (ER) stress has emerged as a critical mechanism involved in leptin resistance and type 2 diabetes in adult individuals. Here, we used a mouse model of maternal obesity to investigate the importance of early life ER stress in the nutritional programming of this metabolic disease. Offspring of obese dams developed glucose intolerance and displayed increased body weight, adiposity, and food intake. Moreover, maternal obesity disrupted the development of melanocortin circuits associated with neonatal hyperleptinemia and leptin resistance. ER stress-related genes were up-regulated in the hypothalamus of neonates born to obese mothers. Neonatal treatment with the ER stress-relieving drug tauroursodeoxycholic acid improved metabolic and neurodevelopmental deficits and reversed leptin resistance in the offspring of obese dams.
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Soyoung Park, Alice Jang, Sébastien Bouret. Maternal obesity-induced endoplasmic reticulum stress causes metabolic alterations and abnormal hypothalamic development in the offspring. PLoS Biology, Public Library of Science, 2020, 18 (3), pp.e3000296. ⟨10.1371/journal.pbio.3000296⟩. ⟨inserm-02513161⟩

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