Wang T, Hartzell D L, Flatt W P, Martin R J, Baile C A
Department of Foods and Nutrition, The University of Georgia, Athens 30602, USA.
Physiol Behav. 1998 Nov 15;65(2):333-41. doi: 10.1016/s0031-9384(98)00173-5.
Obese (Lepr(fa)/Lepr(fa)) Zucker rats have a missense mutation in the leptin receptor gene. One amino acid substitution in the extracellular domain common to all known leptin receptor proteins results from this mutation. Obese Zucker rats are unable to respond behaviorally to leptin which is peripherally administered. However, conflicting reports exist on whether obese Zucker rats can respond to centrally administered leptin. The purpose of this study was to determine whether obese Zucker rats responded behaviorally and metabolically to intracerebroventricularly (i.c.v.) administered leptin and to compare the responses of lean and obese Zucker rats. We found that both lean and obese Zucker rats had similar body weight and food intake responses when administered a single i.c.v. leptin injection in a range of doses (1.25, 2.5, 5, and 10 microg), as well as daily i.c.v. administered leptin for five consecutive days. Both single and daily leptin administration also decreased respiratory quotient (RQ) similarly in lean and obese Zucker rats, indicating mobilization of fat as an energy source for leptin-treated rats. After withdrawal of daily leptin treatment, lean and obese Zucker rats exhibited different recovery responses. It is concluded that obese Zucker rats can respond to exogenous leptin when leptin is delivered into the brain ventricles.
肥胖型（Lepr(fa)/Lepr(fa)） Zucker大鼠的瘦素受体基因存在错义突变。该突变导致所有已知瘦素受体蛋白的胞外域出现一个氨基酸替换。肥胖型Zucker大鼠对外周注射的瘦素无行为反应。然而，关于肥胖型Zucker大鼠对脑室内注射的瘦素是否有反应，存在相互矛盾的报道。本研究的目的是确定肥胖型Zucker大鼠对脑室内注射的瘦素是否有行为和代谢反应，并比较瘦型和肥胖型Zucker大鼠的反应。我们发现，当以一系列剂量（1.25、2.5、5和10微克）单次脑室内注射瘦素以及连续五天每日脑室内注射瘦素时，瘦型和肥胖型Zucker大鼠的体重和食物摄入量反应相似。单次和每日注射瘦素也同样降低了瘦型和肥胖型Zucker大鼠的呼吸商（RQ），表明瘦素处理的大鼠将脂肪作为能量来源进行动员。在停止每日瘦素治疗后，瘦型和肥胖型Zucker大鼠表现出不同的恢复反应。得出的结论是，当将瘦素注入脑室时，肥胖型Zucker大鼠能够对外源性瘦素产生反应。
