Pro-opiomelanocortin gene transfer to the nucleus of the solitary track but not arcuate nucleus ameliorates chronic diet-induced obesity.
Pro-opiomelanocortin gene transfer to the nucleus of the solitary track but not arcuate nucleus ameliorates chronic diet-induced obesity.
复制标题
DOI：
10.1016/j.neuroscience.2010.06.001
复制
发表时间：
2010-09-15
期刊：
影响因子：
3.3
通讯作者：
Scarpace, P. J.
中科院分区：
文献类型：
--
作者：
Zhang, Y.;Rodrigues, E.;Gao, Y. X.;King, M.;Cheng, K. Y.;Erdos, B.;Tumer, N.;Carter, C.;Scarpace, P. J.
短期药理学黑皮质素激活可有效阻止啮齿动物的饮食诱导肥胖（DIO）。然而，是否中枢前阿黑皮素（POMC）基因转移靶向下丘脑或孤束核（NTS）是否可以对抗慢性饮食性肥胖还没有调查。给4周龄的Sprague道利大鼠喂食高脂肪饮食5个月，然后将POMC或对照载体注射到下丘脑或NTS中，并记录体重和食物摄入68天。测量胰岛素敏感性、葡萄糖代谢和中枢交感神经激活的肾上腺指标，并评估自愿轮跑（WR）。NTS POMC治疗减少了累积摄食量，并在68天内持续减轻体重，而下丘脑POMC治疗没有改变累积摄食量，仅在前25天内减轻体重。死亡时，只有NTS-POMC大鼠的脂肪量显著减少。他们还表现出葡萄糖耐量增强，空腹胰岛素降低，QUICK值增加，中枢交感神经激活的肾上腺指标升高。此外，NTS-POMC动物相对于各自的对照组表现出近20%的跑步距离增加，但ARC-POMC大鼠没有。总之，POMC基因转移到NTS引起中度厌食，持续的体重减轻，改善胰岛素敏感性，并增加WR在DIO大鼠的倾向。这些代谢改善可能涉及通过中枢调节的交感神经流出刺激能量消耗。下丘脑中的类似POMC处理具有最小的长期生理或代谢影响。因此，脑干NTS区域的黑皮质素激活有效地改善慢性饮食性肥胖，而下丘脑中的黑皮质素激活则无法做到这一点。
Short-term pharmacological melanocortin activation deters diet-induced obesity (DIO) effectively in rodents. However, whether central pro-opiomelanocortin (POMC) gene transfer targeted to the hypothalamus or hindbrain nucleus of the solitary track (NTS) can combat chronic dietary obesity has not been investigated. Four-week-old Sprague Dawley rats were fed a high fat diet for five months, and then injected with either the POMC or control vector into the hypothalamus or NTS, and body weight and food intake recorded for 68 days. Insulin sensitivity, glucose metabolism and adrenal indicators of central sympathetic activation were measured, and voluntary wheel running (WR) assessed. Whereas the NTS POMC-treatment decreased cumulative food consumption and caused sustained weight reduction over 68 days, the hypothalamic POMC-treatment did not alter cumulative food intake and produced weight loss only in the first 25 days. At death, only the NTS-POMC rats had a significant decrease in fat mass. They also displayed enhanced glucose tolerance, lowered fasting insulin and increased QUICK value, and elevated adrenal indicators of central sympathetic activation. Moreover, the NTS-POMC animals exhibited a near 20% increase in distance ran relative to the respective controls, but the ARC-POMC rats did not. In conclusion, POMC gene transfer to the NTS caused modest anorexia, persistent weight loss, improved insulin sensitivity, and increased propensity for WR in DIO rats. These metabolic improvements may involve stimulation of energy expenditure via centrally regulated sympathetic outflow. The similar POMC treatment in the hypothalamus had minimal long-term physiological or metabolic impact. Thus, melanocortin activation in the brainstem NTS region effectively ameliorates chronic dietary obesity whilst that in the hypothalamus fails to do so.
登录
查看更多内容
影响因子：
2.5
作者：
JOSEPH, SA;PILCHER, WH;BENNETTCLARKE, C
通讯作者：
BENNETTCLARKE, C
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：
15.9
作者：
Nogueiras, Ruben;Wiedmer, Petra;Tschoep, Matthias H.
通讯作者：
Tschoep, Matthias H.
影响因子：
30.8
作者：
Krude, H;Biebermann, H;Grüters, A
通讯作者：
Grüters, A
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