title: Reducing Adiposity in a Critical Developmental Window Has Lasting Benefits in Mice.
abstract: Although most adults can lose weight by dieting, a well-characterized compensatory decrease in energy expenditure promotes weight regain more than 90% of the time. Using mice with impaired hypothalamic leptin signaling as a model of early-onset hyperphagia and obesity, we explored whether this unfavorable response to weight loss could be circumvented by early intervention. Early-onset obesity was associated with impairments in the structure and function of brown adipose tissue mitochondria, which were ameliorated by weight loss at any age. Although decreased sympathetic tone in weight-reduced adults resulted in net reductions in brown adipose tissue thermogenesis and energy expenditure that promoted rapid weight regain, this was not the case when dietary interventions were initiated at weaning. Enhanced energy expenditure persisted even after mice were allowed to resume overeating, leading to lasting reductions in adiposity. These findings reveal a time window when dietary interventions can produce metabolic improvements that are stably maintained.
authors.affiliation: Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
authors.forename: Jaclyn S
authors.initials: JS
authors.lastname: Lerea
authors.affiliation: Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Ring
authors.affiliation: Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
authors.forename: Rim
authors.initials: R
authors.lastname: Hassouna
authors.affiliation: Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
authors.forename: Angie C N
authors.initials: AC
authors.lastname: Chong
authors.affiliation: Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
authors.forename: Klara
authors.initials: K
authors.lastname: Szigeti-Buck
authors.affiliation: Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
authors.affiliation: Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
authors.forename: Lori M
authors.initials: LM
authors.lastname: Zeltser
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000367:Age Factors; D000818:Animals; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D048788:Growth and Development / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D054411:Receptors, Leptin / Q000235:genetics; D022722:Thermogenesis / Q000235:genetics; D013997:Time Factors
chemical_list: D054411:Receptors, Leptin; C515447:leptin receptor, mouse