Huh Jin Young, Park Jeu, Kim Jong In, Park Yoon Jeong, Lee Yun Kyung, Kim Jae Bum
School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
Department of Biophysics and Chemical Biology, Seoul National University, Seoul, Korea.
Diabetes. 2017 Apr;66(4):835-847. doi: 10.2337/db16-1122. Epub 2017 Jan 12.
Adipose tissue inflammation is an important factor in obesity that promotes insulin resistance. Among various cell types in adipose tissue, immune cells actively regulate inflammatory responses and affect whole-body energy metabolism. In particular, invariant natural killer T (iNKT) cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesity-induced inflammation in adipose tissue. However, the molecular mechanisms by which adipose iNKT cells become activated and mediate anti-inflammatory roles in obese adipose tissue have not been thoroughly understood yet. In the current study, we demonstrate that adipocyte CD1d plays a key role in the stimulation of adipose iNKT cells, leading to anti-inflammatory responses in high-fat diet (HFD)-fed mice. Accordingly, adipocyte-specific CD1d-knockout (CD1d) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to α-galactosylceramide-induced iNKT cell activation. Additionally, HFD-fed CD1d mice revealed reduced interleukin-4 expression in adipose iNKT cells and aggravated adipose tissue inflammation and insulin resistance. Collectively, these data suggest that adipocytes could selectively stimulate adipose iNKT cells to mediate anti-inflammatory responses and attenuate excess proinflammatory responses in obese adipose tissue.
脂肪组织炎症是肥胖症中的一个重要因素，可促进胰岛素抵抗。在脂肪组织的各种细胞类型中，免疫细胞积极调节炎症反应并影响全身能量代谢。特别是，不变自然杀伤T（iNKT）细胞通过对抗脂肪组织中肥胖诱导的炎症，有助于减轻全身能量稳态的失调。然而，脂肪iNKT细胞在肥胖脂肪组织中被激活并介导抗炎作用的分子机制尚未完全清楚。在本研究中，我们证明脂肪细胞CD1d在刺激脂肪iNKT细胞中起关键作用，导致高脂饮食（HFD）喂养的小鼠产生抗炎反应。因此，脂肪细胞特异性CD1d基因敲除（CD1d）小鼠脂肪组织中iNKT细胞数量减少，对α-半乳糖神经酰胺诱导的iNKT细胞激活的反应降低。此外，HFD喂养的CD1d小鼠脂肪iNKT细胞中白细胞介素-4表达降低，脂肪组织炎症和胰岛素抵抗加重。总的来说，这些数据表明脂肪细胞可以选择性地刺激脂肪iNKT细胞介导抗炎反应，并减轻肥胖脂肪组织中过度的促炎反应。
