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DOI: 10.2337/diabetes.55.04.06.db05-1250
© 2006 by the American Diabetes Association
Combined Interleukin-6 and Interleukin-1 Deficiency Causes Obesity in Young Mice
1 Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
2 National Institute of Health and Nutrition, Shinjuku, Japan
Address correspondence and reprint requests to Yoichiro Iwakura, DSc, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Toyko 108-8639, Japan. E-mail: iwakura{at}ims.u-tokyo.ac.jp
Abbreviations:
eWAT, epididymal white adipose tissue; FFA, free fatty acid; IL, interleukin; IL-1Ra, IL-1 receptor antagonist; NPY, neuropeptide Y; TAG, triacylglycerol
Proinflammatory cytokines including interleukin (IL)-1 and IL-6 exert pleiotropic effects on the neuro-immuno-endocrine system. Previously, we showed that IL-1 receptor antagonist–deficient (IL-1Ra–/–) mice show a lean phenotype due to an abnormal lipid metabolism. On the contrary, it was reported that IL-6–/– mice exhibit obesity after 6 months of age. This study sought to assess the roles of IL-1 and IL-6 in body weight homeostasis. We generated mice deficient in IL-6 and IL-1Ra (IL-6–/– IL-1Ra–/–) and IL-6, IL-1
, and IL-1ß (IL-6–/– IL-1–/–). IL-6–/– IL-1Ra–/– mice exhibited a lean phenotype, similar to IL-1Ra–/– mice. On the other hand, IL-6–/– IL-1–/– mice became obese as early as 10 weeks of age, while IL-1–/– mice and IL-6–/– mice were normal at this age. The daily food intake was significantly higher in IL-6–/– IL-1–/– mice than in IL-6–/– IL-1+/– mice, while energy expenditure was comparable in these two strains. Acute anorexia induced by peripheral administration of IL-1 was significantly suppressed in IL-6–/– IL-1–/– mice, but not in IL-1–/– mice or IL-6–/– mice compared with wild-type mice. These results indicate that IL-1 and IL-6 are both involved in the regulation of body fat in a redundant manner in young mice.
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