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Leptin actions on food intake and body temperature are mediated by IL-1.
Luheshi G, Gardner J, Rushforth D, Loudon A, Rothwell NJ
Proc Natl Acad Sci U S A. 1999;96( 12):7047-52.
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Abstract
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.
Keyword(s)
Animals; Leptin; Male; Mice; Rats; Rats, Sprague-Dawley; Rats, Zucker; Support, Non-U.S. Gov't; administration & dosage: Antirheumatic Agents; administration & dosage: Proteins; administration & dosage: Sialoglycoproteins; antagonists & inhibitors: Interleukin-1; drug effects: Body Temperature; drug effects: Eating