The Weight-Reducing Effect of an Intracerebroventricular Bolus Injection of Leptin in Genetically Obese fa/fa Rats: Reduced Sensitivity Compared With Lean Animals
The Weight-Reducing Effect of an Intracerebroventricular Bolus Injection of Leptin in Genetically Obese fa/fa Rats: Reduced Sensitivity Compared With Lean Animals
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脑室内推注瘦素对遗传性肥胖 fa/fa 大鼠的减肥效果：与瘦动物相比，敏感性降低
DOI：
10.2337/diab.45.10.1446
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发表时间：
1996
期刊：
影响因子：
7.7
通讯作者：
B. Jeanrenaud
中科院分区：
文献类型：
--
作者：
I. Cusin;F. Rohner;A. Stricker‐Krongrad;B. Jeanrenaud
研究了不同剂量的瘦素脑室注射(Icv)对瘦(FA/FA)大鼠禁食24小时后体重增加和食物摄入量的影响。观察到，与赋形剂注射相比，脑室注射瘦素导致体重增加的剂量依赖性下降，这种差异至少持续了6天。这与注射瘦素后前两天的食物摄入量短暂减少有关。更重要的是，在遗传性肥胖的FA/FA大鼠中也观察到了瘦素的作用，但代价是瘦素浓度增加了两到十倍，这表明瘦素敏感性降低。此外，脑室注射瘦素能够降低瘦型和遗传性肥胖大鼠下丘脑弓状核和侧脑室旁核中神经肽Y(NPY)的水平，尽管肥胖组再次需要更高剂量的瘦素。这些观察结果为NPY和Leptin在控制身体内稳态的调节环路中的含义提供了进一步的证据。这一环在瘦肉和遗传性肥胖的FA/FA大鼠中是起作用的，前提是特别是肥胖组的中枢神经系统中的瘦素水平足够高。由于人类肥胖经常与循环中瘦素水平升高有关，类似于在FA/FA大鼠中描述的瘦素敏感性降低(即，瘦素抵抗)的状态也可能在人类综合征中发生。
The effect of different doses of leptin, given as an intracerebroventricular (ICV) bolus, on body weight gain and food intake was investigated during refeeding, following a 24-h fast in lean (FA/fa) rats. It was observed that ICV leptin resulted in a dose-dependent decrease in body weight gain, compared with vehicle injection, a difference that persisted for at least 6 days. This was associated with a transient reduction in food intake over the first 2 days after leptin injection. More importantly, the effect of leptin was also observed in genetically obese fa/fa rats but at the expense of two to ten times higher leptin concentrations, indicating the presence of decreased leptin sensitivity. Furthermore, ICV leptin injections were able to decrease neuropeptide Y (NPY) levels in the arcuate and paraventricular hypothalamic nuclei in both lean and genetically obese fa/fa rats, although a higher leptin dose was again needed in the obese group. These observations provide further evidence for the implication of NPY and leptin in a regulatory loop controlling body homeostasis. This loop is functional in lean and genetically obese fa/fa rats, provided that leptin levels in the central nervous system are high enough in the obese group, in particular. Since human obesity is frequently associated with elevated circulating leptin levels, a state of decreased leptin sensitivity (i.e., leptin resistance), similar to that described here in fa/fa rats, could possibly occur in human syndromes as well.
遗传性肥胖 Zucker 大鼠下丘脑前神经肽 Y 信使核糖核酸含量增加及其通过食物剥夺的调节。
影响因子：
4.8
作者：
Sanacora,G;Kershaw,M;Finkelstein,JA;White,JD
通讯作者：
White,JD
影响因子：
56.9
作者：
HALAAS, JL;GAJIWALA, KS;FRIEDMAN, JM
通讯作者：
FRIEDMAN, JM
影响因子：
158.5
作者：
Considine, RV;Sinha, MK;Caro, JF
通讯作者：
Caro, JF