IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions.
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.
Matsuki
Taizo
T
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Horai
Reiko
R
Sudo
Katsuko
K
Iwakura
Yoichiro
Y
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism; D004435:Eating; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D007028:Hypothalamic Hormones / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D016207:Cytokines; D007028:Hypothalamic Hormones; D007328:Insulin; D007375:Interleukin-1; D020738:Leptin; D017472:Receptors, Interleukin-1; D014280:Triglycerides; D008049:Lipase