title: Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone.
abstract: Brown adipose tissue (BAT) and brown-like cells in white adipose tissue (WAT) can dissipate energy through thermogenesis, a process mediated by uncoupling protein 1 (UCP1). We investigated whether stress hormones ACTH and corticosterone contribute to BAT activation and browning of WAT. ACTH and corticosterone were studied in male mice exposed to 4 or 23°C for 24 h. Direct effects were studied in T37i mouse brown adipocytes and primary cultured murine BAT and inguinal WAT (iWAT) cells. In vivo effects were studied using (18)F-deoxyglucose positron emission tomography. Cold exposure doubled serum ACTH concentrations (P=0.03) and fecal corticosterone excretion (P=0.008). In T37i cells, ACTH dose-dependently increased Ucp1 mRNA (EC50=1.8 nM) but also induced Ucp1 protein content 88% (P=0.02), glycerol release 32% (P=0.03) and uncoupled respiration 40% (P=0.003). In cultured BAT and iWAT, ACTH elevated Ucp1 mRNA by 3-fold (P=0.03) and 3.7-fold (P=0.01), respectively. In T37i cells, corticosterone prevented induction of Ucp1 mRNA and Ucp1 protein by both ACTH and norepinephrine in a glucocorticoid receptor (GR)-dependent fashion. ACTH and GR antagonist RU486 independently doubled BAT (18)F-deoxyglucose uptake (P=0.0003 and P=0.004, respectively) in vivo. Our results show that ACTH activates BAT and browning of WAT while corticosterone counteracts this.
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, and j.vandenbeukel@erasmusmc.nl.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: van den Beukel
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, and.
authors.forename: Aldo
authors.initials: A
authors.lastname: Grefhorst
authors.affiliation: Endocrinology Unit and Centro di Ricerca Biomedica Applicata, Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; and.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Quarta
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, and.
authors.forename: Jacobie
authors.initials: J
authors.lastname: Steenbergen
authors.affiliation: Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands;
authors.forename: Pier G
authors.initials: PG
authors.lastname: Mastroberardino
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud, Faculté de Médecine Paris-Sud, Unité Mixte de Recherche (UMR) S693, Le Kremlin Bicêtre, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, and.
authors.forename: Patric J
authors.initials: PJ
authors.lastname: Delhanty
authors.affiliation: Endocrinology Unit and Centro di Ricerca Biomedica Applicata, Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; and.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazza
authors.affiliation: Endocrinology Unit and Centro di Ricerca Biomedica Applicata, Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; and.
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, and.
authors.forename: Aart Jan
authors.initials: AJ
authors.lastname: van der Lely
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, and.
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011965:Receptors, Glucocorticoid; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: HPA axis; cold exposure; hypothalamic-pituitary-adrenal axis; metabolism