Division of Cellular Immunology, German Cancer Research Center, Heidelberg, D-69120, Germany.
Institute for Diabetes and Cancer IDC, Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Cell Metab. 2015 May 5;21(5):678-91. doi: 10.1016/j.cmet.2015.04.013.
Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome.
肥胖、胰岛素抵抗和相关病理与免疫介导的慢性炎症有关。Kit 突变小鼠对饮食诱导的肥胖及其相关合并症具有保护作用，而这种表型以前归因于它们缺乏肥大细胞。我们对依赖 Kit 的 Kit(W/Wv)和非依赖 Kit 的 Cpa3(Cre/+)肥大细胞缺陷小鼠品系进行了全面的代谢分析，采用了饮食诱导或遗传（Lep(Ob/Ob)背景）肥胖模型。我们的结果表明，肥大细胞缺乏（不伴有 Kit 突变）在调节体重增加或胰岛素抵抗方面不起作用。此外，我们提供的证据表明，Kit 突变小鼠观察到的代谢表型虽然与肥大细胞无关，但受到免疫调节。我们的数据强调了明确的肥大细胞缺陷模型的价值，这些模型可用于确定这种神秘细胞在免疫介导的病理中的参与作用，并确定 Kit 是代谢综合征发病机制中的关键造血因子。
