Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice.
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-1alpha, and IL-1beta (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.
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Toyko 108-8639, Japan.
Dai
D
Chida
Toshimasa
T
Osaka
Okito
O
Hashimoto
Yoichiro
Y
Iwakura
D000375:Aging; D000818:Animals; D001835:Body Weight; D002149:Energy Intake; D007375:Interleukin-1 / Q000172:deficiency* / Q000235:genetics; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013851:Thinness / Q000235:genetics / Q000276:immunology; D015430:Weight Gain
D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1