Diabetes Obesity Center for Excellence, Division of Metabolism, Endocrinology and Nutrition, University of Washington, 850 Republican Street Box 35805, Seattle, WA 98109, USA.
Division of Cardiology, University of Washington, Seattle, WA 98195, USA.
Int J Mol Sci. 2018 Feb 8;19(2):510. doi: 10.3390/ijms19020510.
Obesity is a chronic inflammatory state characterized by altered levels of adipose tissue immune cell populations. Natural killer T (NKT) cells are CD1d restricted lymphocyte subsets that recognize lipid antigens whose level decreases in obese adipose tissue. However, studies in mice with deficiency or increased levels of NKT cells have yielded contradictory results, so the exact role of these cells in obesity and adipose tissue inflammation is not yet established. We previously showed that mice with excess invariant NKT (iNKT) cells demonstrate significant weight gain, adiposity, metabolic abnormalities, and atherosclerosis. The current study evaluates the effects of NKT cell deficiency on obesity, associated metabolic changes, and atherosclerosis in (lacking iNKT cells) and (lacking invariant and type II NKT cells) mice, and control mice were fed an obesogenic diet (high fat, sucrose, cholesterol) for 16 weeks. Contrary to expectations, mice gained significantly more weight than or mice, developed hypertriglyceridemia, and had worsened adipose tissue inflammation. All the mice developed insulin resistance and hepatic triglyceride accumulation. mice also had increased atherosclerotic lesion area. Our findings suggest that iNKT cells exacerbates the metabolic, inflammatory, and atherosclerotic features of diet-induced obesity. Further work is required to unravel the paradox of an apparently similar effect of iNKT cell surplus and depletion on obesity.
肥胖是一种慢性炎症状态，其特征是脂肪组织免疫细胞群体的改变。自然杀伤 T（NKT）细胞是 CD1d 限制的淋巴细胞亚群，可识别脂质抗原，而肥胖脂肪组织中这些抗原的水平降低。然而，在 NKT 细胞缺乏或水平增加的小鼠中进行的研究得出了相互矛盾的结果，因此这些细胞在肥胖和脂肪组织炎症中的确切作用尚未确定。我们之前曾表明，具有过多不变自然杀伤 T（iNKT）细胞的 小鼠表现出明显的体重增加、肥胖、代谢异常和动脉粥样硬化。本研究评估了 NKT 细胞缺乏对肥胖、相关代谢变化和动脉粥样硬化的影响，在 （缺乏 iNKT 细胞）和 （缺乏不变和 II 型 NKT 细胞）小鼠以及对照小鼠中，喂食致肥胖饮食（高脂肪、蔗糖、胆固醇）16 周。出乎意料的是， 小鼠比 或 小鼠体重增加明显更多，发生高甘油三酯血症，并且脂肪组织炎症加重。所有小鼠均发生胰岛素抵抗和肝甘油三酯蓄积。 小鼠还增加了动脉粥样硬化病变面积。我们的研究结果表明，iNKT 细胞加剧了饮食诱导肥胖的代谢、炎症和动脉粥样硬化特征。需要进一步的工作来阐明 iNKT 细胞过剩和耗竭对肥胖的影响明显相似这一悖论。
