Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation
Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation
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DOI：
10.1210/en.2007-0621
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发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Bartness, Timothy J.
中科院分区：
文献类型：
--
作者：
Brito, Marcia N.;Brito, Nilton A.;Bartness, Timothy J.
黑皮质素与能量摄入/消耗的控制有关。中枢给药的美拉诺坦II（MTII），一种合成的黑皮质素3/4受体激动剂，减少肥胖超过食物摄入量减少的解释。黑素皮质素-4受体（MC 4-R）mRNA在西伯利亚仓鼠的交感神经系统（SNS）流出神经元到白色脂肪组织（WAT）上表达，表明其在脂质动员中的作用。因此，我们使用去甲肾上腺素周转率（NETO）作为交感神经驱动的量度，测试了第三脑室注射MTII是否增加了对WAT和肩胛间棕色脂肪组织（IBAT）的交感神经驱动。我们还检测了MTII诱导的脂解相关WAT基因表达（β 3-肾上腺素受体，激素敏感脂肪酶）和IBAT产热（β 3-肾上腺素受体，解偶联蛋白-1）的变化。最后，我们测试了第三次心室注射MTII，一种高度选择性的MC 4-R激动剂（环[β-Ala-His-D-Phe-Arg-Trp-Glu] NH 2）是否增加或降低植入皮下IBAT温度应答器的仓鼠的IBAT温度。中央给药MTII引起对WAT和IBAT的不同交感神经驱动（腹股沟WAT、背皮下WAT和IBAT NETO增加，但附睾WAT和腹膜后WAT NETO不增加）。MTII还增加了循环中的脂解产物游离脂肪酸和甘油的浓度，但不增加血浆儿茶酚胺，这表明脂质通过WAT SNS神经支配而不是通过肾上腺髓质儿茶酚胺动员。WAT或IBAT基因表达在很大程度上不受急性MTII治疗的影响，但IBAT温度增加MTII和MC 4-R激动剂和Agouti相关蛋白降低。总的来说，这是第一次证明中枢黑皮质素激动剂通过SNS刺激WAT脂解，并证实了黑皮质素诱导的BAT产热变化。
Melanocortins are implicated in the control of energy intake/expenditure. Centrally administered melanotan II (MTII), a synthetic melanocortin 3/4-receptor agonist, decreases adiposity beyond that accountable by food intake decreases. Melanocortin-4 receptor (MC4-R) mRNA is expressed on sympathetic nervous system (SNS) outflow neurons to white adipose tissue (WAT) in Siberian hamsters, suggesting a role in lipid mobilization. Therefore, we tested whether third ventricular injections of MTII increased sympathetic drive to WAT and interscapular brown adipose tissue (IBAT) using norepinephrine turnover (NETO) as a measure of sympathetic drive. We also tested for MTII-induced changes in lipolysis-related WAT gene expression (beta 3-adrenoceptors, hormone sensitive lipase) and IBAT thermogenesis (beta 3-adrenoceptor, uncoupling protein-1). Finally, we tested whether third ventricularly injected MTII, a highly selective MC4-R agonist (cyclo[beta-Ala-His-D-Phe-Arg-Trp-Glu]NH2) increased or agouti-related protein decreased IBAT temperature in hamsters implanted with sc IBAT temperature transponders. Centrally administered MTII provoked differential sympathetic drives to WAT and IBAT ( increased inguinal WAT, dorsosubcutaneous WAT and IBAT NETO, but not epididymal WAT and retroperitoneal WAT NETO). MTII also increased circulating concentrations of the lipolytic products free fatty acids and glycerol but not plasma catecholamines, suggesting lipid mobilization via WAT SNS innervation and not via adrenal medullary catecholamines. WAT or IBAT gene expression was largely unaffected by acute MTII treatment, but IBAT temperature was increased by MTII and the MC4-R agonist and decreased by agouti-related protein. Collectively, this is the first demonstration of central melanocortin agonist stimulation of WAT lipolysis through the SNS and confirms melanocortin-induced changes in BAT thermogenesis.