title: Decreased fat mass in interleukin-1 receptor antagonist-deficient mice: impact on adipogenesis, food intake, and energy expenditure.
abstract: Interleukin (IL)-1 is a regulator of inflammation but is also implicated in the control of energy homeostasis. Because the soluble IL-1 receptor antagonist (IL-1Ra) is markedly increased in the serum of obese patients and is overexpressed in white adipose tissue in obesity, we studied the metabolic consequences of genetic IL-1Ra ablation in mice. We have shown that IL-1Ra-/- mice have a lean phenotype due to decreased fat mass, related to a defect in adipogenesis and increased energy expenditure. The adipocytes were smaller in these animals, and the expression of genes involved in adipogenesis was reduced. Energy expenditure as measured by indirect calorimetry was elevated, and weight loss in response to a 24-h fast was increased in IL-1Ra-/- animals compared with wild-type mice. Lipid oxidation of IL-1Ra-/- mice was higher during the light period, reflecting their reduction in diurnal food intake. Interestingly, IL-1Ra-/- and IL-1Ra+/- mice presented an attenuation in high-fat diet-induced caloric hyperphagia, indicating a better adaptation to hypercaloric alimentation, which is in line with the role of IL-1Ra as a mediator of leptin resistance. Taken together, we show that IL-1Ra is an important regulator of adipogenesis, food intake, and energy expenditure.
authors.affiliation: Endocrine Unit, Department of Internal Medicine, University Hospital Geneva, 24, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Somm
authors.forename: Elvire
authors.initials: E
authors.lastname: Henrichot
authors.forename: Agnès
authors.initials: A
authors.lastname: Pernin
authors.forename: Cristiana E
authors.initials: CE
authors.lastname: Juge-Aubry
authors.forename: Patrick
authors.initials: P
authors.lastname: Muzzin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
authors.forename: Martin J H
authors.initials: MJ
authors.lastname: Nicklin
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Meier
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000502:physiology; D000818:Animals; D001823:Body Composition; D002149:Energy Intake; D004734:Energy Metabolism; D005784:Gene Amplification; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007438:Introns; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism; D012795:Sialoglycoproteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain; D015431:Weight Loss / Q000502:physiology*
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins