title: Age-Dependent Control of Energy Homeostasis by Brown Adipose Tissue in Progeny Subjected to Maternal Diet-Induced Fetal Programming.
abstract: Epidemiological and animal studies show that deleterious maternal environments predispose aging offspring to metabolic disorders and type 2 diabetes. Young progenies in a rat model of maternal low-protein (LP) diet are 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 the 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 β-cell function and hyperglycemia and place it as a critical regulator of fetal programming of adult metabolic disease.
authors.affiliation: Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dumortier
authors.affiliation: Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Roger
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, iBV, Nice, France.
authors.forename: Didier F
authors.initials: DF
authors.lastname: Pisani
authors.affiliation: Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Casamento
authors.affiliation: Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gautier
authors.affiliation: Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
authors.forename: Hereroa
authors.initials: H
authors.lastname: Johnston
authors.affiliation: Université Côte d'Azur, INSERM, CNRS, IRCAN, Nice, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, iBV, Nice, France.
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
authors.affiliation: Université Clermont, INRA, Clermont-Ferrand, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Jousse
authors.affiliation: Université Clermont, INRA, Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fafournoux
authors.affiliation: CRCHUM and Montreal Diabetes Research Center and Departments of Nutrition and Biochemistry and Molecular Medicine, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
authors.affiliation: Université Côte d'Azur, CHU, INSERM, CNRS, IRCAN, Nice, France hinault@unice.fr vanobbeg@unice.fr.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hinault
authors.affiliation: Université Côte d'Azur, CHU, INSERM, CNRS, IRCAN, Nice, France hinault@unice.fr vanobbeg@unice.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Van Obberghen
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000601:surgery; D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001833:Body Temperature Regulation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D059305:Diet, High-Fat; D018753:Diet, Protein-Restricted; D004734:Energy Metabolism; D005260:Female; D047109:Fetal Development; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006943:Hyperglycemia / Q000378:metabolism*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008066:Lipolysis; D008297:Male; D009765:Obesity / Q000378:metabolism*; D019518:Postprandial Period; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides