Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity
Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity
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DOI：
10.1101/gad.329557.119
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发表时间：
2019-12-01
影响因子：
10.5
通讯作者：
Kim, Jae Bum
中科院分区：
文献类型：
--
作者：
Park, Jeu;Huh, Jin Young;Kim, Jae Bum
在肥胖症中，脂肪组织经历动态重塑过程，例如脂肪细胞肥大、缺氧、免疫应答和脂肪细胞死亡。然而，是否以及如何不变的自然杀伤T（iNKT）细胞有助于脂肪组织重塑是难以捉摸的。在这项研究中，我们证明了iNKT细胞去除不健康的脂肪细胞并刺激健康脂肪细胞的分化。在肥胖脂肪组织中，iNKT细胞大量存在于死亡脂肪细胞附近。FasL阳性脂肪iNKT细胞发挥细胞毒性作用，以消除肥大和促炎Fas阳性脂肪细胞。此外，体内脂肪细胞谱系示踪小鼠模型显示，α-半乳糖神经酰胺激活iNKT细胞促进脂肪细胞更新，最终导致脂肪组织中胰岛素依赖性葡萄糖摄取能力增强。总的来说，我们的数据提出了一个新的作用，脂肪iNKT细胞在调节脂肪细胞的周转肥胖。
In obesity, adipose tissue undergoes dynamic remodeling processes such as adipocyte hypertrophy, hypoxia, immune responses, and adipocyte death. However, whether and how invariant natural killer T (iNKT) cells contribute to adipose tissue remodeling are elusive. In this study, we demonstrate that iNKT cells remove unhealthy adipocytes and stimulate the differentiation of healthy adipocytes. In obese adipose tissue, iNKT cells were abundantly found nearby dead adipocytes. FasL-positive adipose iNKT cells exerted cytotoxic effects to eliminate hypertrophic and pro-inflammatory Fas-positive adipocytes. Furthermore, in vivo adipocyte-lineage tracing mice model showed that activation of iNKT cells by alpha-galactosylceramide promoted adipocyte turnover, eventually leading to potentiation of the insulin-dependent glucose uptake ability in adipose tissue. Collectively, our data propose a novel role of adipose iNKT cells in the regulation of adipocyte turnover in obesity.