Somm Emmanuel, Henrichot Elvire, Pernin Agnès, Juge-Aubry Cristiana E, Muzzin Patrick, Dayer Jean-Michel, Nicklin Martin J H, Meier Christoph A
Endocrine Unit, Department of Internal Medicine, University Hospital Geneva, 24, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland.
Diabetes. 2005 Dec;54(12):3503-9. doi: 10.2337/diabetes.54.12.3503.
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.
白细胞介素（IL）-1是炎症的调节因子，但也参与能量稳态的控制。由于可溶性IL-1受体拮抗剂（IL-1Ra）在肥胖患者血清中显著增加，且在肥胖患者的白色脂肪组织中过度表达，我们研究了小鼠基因敲除IL-1Ra的代谢后果。我们发现，IL-1Ra基因敲除小鼠因脂肪量减少而表现出消瘦的表型，这与脂肪生成缺陷和能量消耗增加有关。这些动物的脂肪细胞较小，参与脂肪生成的基因表达减少。通过间接测热法测量的能量消耗增加，与野生型小鼠相比，IL-1Ra基因敲除动物在禁食24小时后的体重减轻增加。IL-1Ra基因敲除小鼠在光照期的脂质氧化更高，这反映了它们日间食物摄入量的减少。有趣的是，IL-1Ra基因敲除小鼠和杂合子小鼠在高脂饮食诱导的热量摄入过多方面表现出减弱，表明它们对高热量饮食有更好的适应性，这与IL-1Ra作为瘦素抵抗介质的作用一致。综上所述，我们表明IL-1Ra是脂肪生成、食物摄入和能量消耗的重要调节因子。
