The Journal of Experimental Medicine
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Published 15 September 2003. doi:10.1084/jem.20030299
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© Rockefeller University Press, 0022-1007/2003/9/877 $5.00
The Journal of Experimental Medicine, Volume 198, Number 6, 877-888

IL-1 Plays an Important Role in Lipid Metabolism by Regulating Insulin Levels under Physiological Conditions

Taizo Matsuki, Reiko Horai, Katsuko Sudo and Yoichiro Iwakura

Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

Address correspondence to Yoichiro Iwakura, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5536; Fax: 81-3-5449-5430; email: iwakura{at}ims.u-tokyo.ac.jp

IL-1 is a proinflammatory cytokine that plays important roles in inflammation. However, the role of this cytokine under physiological conditions is not known completely. In this paper, we analyzed the role of IL-1 in maintaining body weight because IL-1 receptor antagonist–deficient (IL-1Ra-/-) mice, in which excess IL-1 signaling may be induced, show a lean phenotype. Body fat accumulation was impaired in IL-1Ra-/- mice, but feeding behavior, expression of hypothalamic factors involved in feeding control, energy expenditure, and heat production were normal. When IL-1Ra-/- mice were treated with monosodium glutamate (MSG), which causes obesity in wild-type mice by ablating cells in the hypothalamic arcuate nucleus, they were resistant to obesity, indicating that excess IL-1 signaling antagonizes the effect of MSG-sensitive neuron deficiency. IL-1Ra-/- mice showed decreased weight gain when they were fed the same amount of food as wild-type mice, and lipid accumulation remained impaired even when they were fed a high-fat diet. Interestingly, serum insulin levels and lipase activity were low in IL-1Ra-/- mice, and the insulin levels were low in contrast to wild-type mice after MSG treatment. These observations suggest that IL-1 plays an important role in lipid metabolism by regulating insulin levels and lipase activity under physiological conditions.

Key Words: IL-1–deficient mouse • IL-1 receptor antagonist–deficient mouse • obese • skinny model • energy homeostasis


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