Luheshi G N, Gardner J D, Rushforth D A, Loudon A S, Rothwell N J
School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom.
Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):7047-52. doi: 10.1073/pnas.96.12.7047.
Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin failed to affect food intake or body temperature in obese (fa/fa) Zucker rats, which posses a defective leptin receptor. Furthermore, injection of leptin increased levels of the proinflammatory cytokine IL-1beta in the hypothalamus of normal Sprague-Dawley rats. Central injection of IL-1 receptor antagonist (IL-1ra) inhibited the suppression of food intake caused by central or peripheral injection of leptin (60 and 84%, respectively) and abolished the leptin-induced increase in body temperature in both cases. Mice lacking (gene knockout) the main IL-1 receptor (80 kDa, R1) responsible for IL-1 actions showed no reduction in food intake in response to leptin. These data indicate that leptin actions in the brain depend on IL-1, and we show further that the effect of leptin on fever, but not food intake, is abolished by a cyclooxygenase inhibitor. Thus, we propose that in addition to its role in body weight regulation, leptin may mediate neuroimmune responses via actions in the brain dependent on release of IL-1 and prostaglandins.
瘦素通过作用于大脑调节食欲和能量消耗来调控能量平衡，并且与细胞因子如白细胞介素 -1 具有共同特性。我们在此报告，向大鼠脑室内或外周注射瘦素会引起核心体温显著的剂量依赖性升高以及食欲抑制。瘦素对肥胖（fa/fa） Zucker 大鼠的食物摄入量或体温没有影响，这类大鼠存在有缺陷的瘦素受体。此外，注射瘦素会使正常的斯普拉格 - 道利大鼠下丘脑促炎细胞因子白细胞介素 -1β 的水平升高。脑室内注射白细胞介素 -1 受体拮抗剂（IL-1ra）抑制了由脑室内或外周注射瘦素所引起的食物摄入量抑制（分别为 60%和 84%），并且在这两种情况下都消除了瘦素诱导的体温升高。缺乏负责白细胞介素 -1 作用的主要白细胞介素 -1 受体（80 kDa，R1）的基因敲除小鼠对瘦素没有出现食物摄入量减少的情况。这些数据表明瘦素在大脑中的作用依赖于白细胞介素 -1，并且我们进一步表明，环氧化酶抑制剂消除了瘦素对发热的影响，但未消除对食物摄入的影响。因此，我们提出，除了其在体重调节中的作用外，瘦素可能通过依赖于白细胞介素 -1 和前列腺素释放的大脑作用来介导神经免疫反应。
