Leptin actions on food intake and body temperature are mediated by IL-1
Leptin actions on food intake and body temperature are mediated by IL-1
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DOI：
10.1073/pnas.96.12.7047
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发表时间：
1999-06-08
影响因子：
11.1
通讯作者：
Rothwell, NJ
中科院分区：
文献类型：
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作者：
Luheshi, GN;Gardner, JD;Rothwell, NJ
瘦素通过其在大脑中对食欲和能量消耗的作用来调节能量平衡，并且还与细胞因子如IL-1共享特性。我们在这里报告，将瘦素注射到大鼠脑室内或外周，诱导核心体温的显著剂量依赖性增加以及食欲抑制，瘦素未能影响肥胖（fa/fa）Zucker大鼠的食物摄入或体温，这是一种有缺陷的瘦素受体。此外，注射瘦素增加了正常Sprague-Dawley大鼠下丘脑中促炎细胞因子IL-1 β的水平。中枢注射IL-1受体拮抗剂（IL-1 ra）抑制中枢或外周注射瘦素引起的摄食抑制（分别为60%和84%），并在两种情况下消除瘦素诱导的体温升高。缺乏（基因敲除）负责IL-1作用的主要IL-1受体（80 kDa，R1）的小鼠对瘦素没有表现出食物摄入的减少。这些数据表明，瘦素在大脑中的作用依赖于IL-1，我们进一步表明，瘦素对发热的影响，但不是食物摄入，被环氧合酶抑制剂消除。因此，我们建议，除了其在体重调节中的作用，瘦素可能介导的神经免疫反应，通过在大脑中的行动依赖于释放IL-1和白介素。
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-1 beta 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.