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Age-Dependent Control Of Energy Homeostasis by Brown Adipose Tissue in Progeny Subjected to Maternal Diet-Induced Fetal Programming

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Dumortier, Olivier | Roger, Estelle | Pisani, Didier F | Casamento, Virginie | Gautier, Nadine | Lebrun, Patricia | Johnston, Hereroa | Lopez, Pascal | Amri, Ez-Zoubir | Jousse, Céline | Fafournoux, Pierre | Prentki, Marc | Hinault, Charlotte | van Obberghen, Emmanuel

Edité par CCSD ; American Diabetes Association -

E.-Z.A. was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373). M.P. holds the Canada Research Chair in Diabetes and Metabolism. E.V.O. was supported by INSERM, Universite Cote d'Azur, Conseil Regional PACA, Conseil General des Alpes-Maritimes, Aviesan/AstraZeneca (Diabetes and the vessel wall injury program), the Agence Nationale de la Recherche (ANR) through ANR-RPV12004AAA (DIAMIR) "Investments for the Future" LABEX SIGNALIFE ANR-11-LABX-0028-01, and the European Foundation for the Study of Diabetes (EFSD/Lilly, European Diabetes Research Program). E.V.O. team members are affiliated with the FHU OncoAge (http://www.oncoage.org/). Epidemiological and animal studies show that deleterious maternal environments predispose aging offspring to metabolic disorders and type 2 diabetes. Young progeny in a rat model of maternal low protein diet (LP) is normoglycemic despite collapsed insulin secretion. However, without further worsening of the insulin secretion defect glucose homeostasis deteriorates in aging LP descendants. Here we report that normoglycemic and insulinopenic 3-month-old LP progeny shows increased body temperature and energy dissipation in association with enhanced brown adipose tissue (BAT) activity. In addition, it is protected against a cold challenge and high fat diet (HFD)-induced obesity with associated insulin resistance and hyperglycemia. Surgical BAT ablation in 3-month-old LP offspring normalizes body temperature and causes postprandial hyperglycemia. At 10 months BAT activity declines in LP progeny with appearance of reduced protection to HFD-induced obesity; at 18 months LP progeny displays a BAT activity comparable to control offspring and insulin resistance and hyperglycemia occur. Together our findings identify BAT as a decisive physiological determinant of the onset of metabolic dysregulation in offspring predisposed to altered beta cell function and hyperglycemia, and place it as a critical regulator of fetal programming of adult metabolic disease

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