Simultaneous POMC gene transfer to hypothalamus and brainstem increases physical activity, lipolysis and reduces adult-onset obesity.
Simultaneous POMC gene transfer to hypothalamus and brainstem increases physical activity, lipolysis and reduces adult-onset obesity.
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DOI：
10.1111/j.1460-9568.2011.07633.x
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Scarpace PJ
中科院分区：
文献类型：
--
作者：
Zhang Y;Rodrigues E;Li G;Gao Y;King M;Carter CS;Tumer N;Cheng KY;Scarpace PJ
阿片黑素皮质素原(POMC)神经元存在于下丘脑的弓状核(ARC)和脑干的孤束核(NTS)两个部位。早期的药理学和POMC基因转移研究表明，仅在这两个部位激活黑素皮质素就可以改善胰岛素敏感性并减少肥胖。本研究首次探讨了同时将POMC基因转移到两个部位对成年肥胖老年F344xBN大鼠能量代谢的调节作用。配对喂养被包括在内，以揭示独立于食物的POMC对能量消耗的影响。我们将编码POMC或绿色荧光蛋白的腺相关病毒引入22月龄大鼠的两个脑区，然后记录摄食量和体重，评估氧耗，血清瘦素、胰岛素和血糖，测试自愿车轮跑，分析POMC表达，并检测棕色和白色脂肪组织中的脂肪代谢。终止时下丘脑和NTS区的POMC基因表达均显著增加。与配对喂养相比，POMC导致持续的体重减轻和额外的脂肪损失，降低空腹胰岛素和血糖，提高白色脂肪激素敏感脂肪酶活性和棕色脂肪解偶联蛋白1水平。通过车轮跑步评估，POMC动物的跑步距离是对照组或成对喂养的大鼠的两倍。因此，双部位POMC治疗有效地改善了成人发病的肥胖症，包括持续约60天的中度吞噬减少，增强脂肪分解和产热，并以自愿车轮跑步的形式增加体力活动。后一项发现为对抗与年龄相关的体力活动减少提供了线索。
Pro-opiomelanocortin (POMC) neurons are identified in two brain sites, the arcuate nucleus (ARC) of the hypothalamus and nucleus of the solitary tract (NTS) in brainstem. Earlier pharmacological and POMC gene transfer studies demonstrate melanocortin activation in either site alone improves insulin sensitivity and reduces obesity. The present study, for the first time, investigated the long-term efficacy of POMC gene transfer concurrently into both sites in the regulation of energy metabolism in aged F344xBN rats bearing adult-onset obesity. Pair feeding was included to reveal food-independent POMC impact on energy expenditure. We introduced adeno-associated virus encoding either POMC or green fluorescence protein to the two brain areas in 22-month-old rats, then recorded food intake and body weight, assessed oxygen consumption, serum leptin, insulin and glucose, tested voluntary wheel running, analyzed POMC expression, and examined fat metabolism in brown and white adipose tissues. POMC mRNA was significantly increased in both the hypothalamus and NTS region at termination. Relative to pair feeding, POMC caused sustained weight reduction and additional fat loss, lowered fasting insulin and glucose, and augmented white fat hormone-sensitive lipase activity and brown fat uncoupling protein 1 level. By wheel running assessment, the POMC-animals ran twice the distance as the control or pair-fed rats. Thus, the dual-site POMC treatment ameliorated adult-onset obesity effectively, involving a moderate hypophagia lasting ~ 60 days, enhanced lipolysis and thermogenesis, and increased physical activity in the form of voluntary wheel running. The latter finding provides a clue for countering age-related decline in physical activity.
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影响因子：
--
作者：
Kotz, CM;Teske, JA;Wang, CF
通讯作者：
Wang, CF
DOI：
10.1152/ajpendo.00451.2006
发表时间：
2007-07-01
影响因子：
5.1
作者：
Li, Gang;Zhang, Yi;Scarpace, Philip J.
通讯作者：
Scarpace, Philip J.
影响因子：
3.3
作者：
Li, G;Klein, RL;Scarpace, PJ
通讯作者：
Scarpace, PJ
DOI：
10.1152/ajpregu.2001.281.2.r444
发表时间：
2001-08-01
影响因子：
2.8
作者：
Hwa, JJ;Ghibaudi, L;Parker, EM
通讯作者：
Parker, EM
影响因子：
5.2
作者：
Chen BT;Hopf FW;Bonci A
通讯作者：
Bonci A