Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone
Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone
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DOI：
10.1096/fj.14-254839
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发表时间：
2014-11-01
期刊：
影响因子：
4.8
通讯作者：
Themmen, Axel P. N.
中科院分区：
文献类型：
--
作者：
van den Beukel, Johanna C.;Grefhorst, Aldo;Themmen, Axel P. N.
棕色脂肪组织 (BAT) 和白色脂肪组织 (WAT) 中的棕色样细胞可以通过产热作用耗散能量，这是由解偶联蛋白 1 (UCP1) 介导的过程。我们研究了应激激素 ACTH 和皮质酮是否会导致 BAT 激活和 WAT 褐变。在暴露于 4 或 23 摄氏度 24 小时的雄性小鼠中研究了 ACTH 和皮质酮。在 T37i 小鼠棕色脂肪细胞和原代培养的小鼠 BAT 和腹股沟 WAT (iWAT) 细胞中研究了直接效应。使用F-18-脱氧葡萄糖正电子发射断层扫描研究体内效应。冷暴露使血清 ACTH 浓度（P=0.03）和粪便皮质酮排泄量（P=0.008）翻倍。在T37i细胞中，ACTH剂量依赖性地增加Ucp1 mRNA（EC50 = 1.8 nM），但也诱导Ucp1蛋白含量88％（P = 0.02），甘油释放32％（P = 0.03）和解偶联呼吸40％（P = 0.003）。在培养的 BAT 和 iWAT 中，ACTH 分别使 Ucp1 mRNA 升高 3 倍（P=0.03）和 3.7 倍（P=0.01）。在 T37i 细胞中，皮质酮以糖皮质激素受体 (GR) 依赖性方式阻止 ACTH 和去甲肾上腺素诱导 Ucp1 mRNA 和 Ucp1 蛋白。 ACTH 和 GR 拮抗剂 RU486 在体内独立地使 BAT F-18-脱氧葡萄糖摄取加倍（分别为 P=0.0003 和 P=0.004）。我们的结果表明，ACTH 激活 BAT 和 WAT 褐变，而皮质酮则抵消此作用。 Van den Beukel, J. C.、Grefhorst, A.、Quarta, C.、Steenbergen, J.、Mastroberardino, P. G.、Lombes, M.、Delhanty, P. J.、Mazza, R.、Pagotto, U.、van der Lely, A. J.、Themmen, A. P.N. 促肾上腺皮质激素（ACTH）对棕色脂肪组织的直接激活作用被皮质酮减弱。
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 degrees 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 F-18-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 F-18-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., Lombes, 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.