Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone.
FASEB j.. 2014-08-01; 28(11): 4857-4867
DOI: 10.1096/fj.14-254839
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van den Beukel JC(1), Grefhorst A(2), Quarta C(3), Steenbergen J(2),
Mastroberardino PG(4), Lombès M(5), Delhanty PJ(2), Mazza R(3), Pagotto U(3), van
der Lely AJ(2), Themmen AP(2).
Author information:
(1)Department of Internal Medicine, Section of Endocrinology, and
.
(2)Department of Internal Medicine, Section of Endocrinology, and.
(3)Endocrinology Unit and Centro di Ricerca Biomedica Applicata, Department of
Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna,
Bologna, Italy; and.
(4)Department of Genetics, Erasmus University Medical Center, Rotterdam, The
Netherlands;
(5)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.
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.
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