Leptin actions on food intake and body temperature are mediated by IL-1.
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.
Luheshi
G N
GN
School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom.
Gardner
J D
JD
Rushforth
D A
DA
Loudon
A S
AS
Rothwell
N J
NJ
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001831:Body Temperature / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020738:Leptin; D008297:Male; D051379:Mice; D011506:Proteins / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D012795:Sialoglycoproteins / Q000008:administration & dosage
D018501:Antirheumatic Agents; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020738:Leptin; D011506:Proteins; D012795:Sialoglycoproteins