Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone. Issue 11 (1st August 2014)

• Record Type: Journal Article
• Authors: van den Beukel, Johanna C.; Grefhorst, Aldo; Quarta, Carmelo; Steenbergen, Jacobie; Mastroberardino, Pier G.; Lombès, Marc; Delhanty, Patric J.; Mazza, Roberta; Pagotto, Uberto; van der Lely, Aart Jan; Themmen, Axel P. N.
• Is Part Of: FASEB journal. Volume 28:Issue 11(2014)
• Page Start: 4857
• Page End: 4867
• Publication Date: 2014-08-01
• Subjects: HPA axis -- hypothalamic‐pituitary‐adrenal axis -- metabolism -- cold exposure; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.14-254839
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract : Brown adipose tissue (BAT) and brownlike 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.—Van den Beukel, J. C., Grefhorst, A., Quarta, C., Steenbergen, J., Mastroberardino, P. G., Lombès, M., Delhanty, P. J., Mazza, R., Pagotto, U., van der Lely, A. J., Themmen, A. P. N., Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone. FASEB J. 28, 4857–4867 (2014). www.fasebj.org