Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity
Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity
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DOI：
10.2337/db16-1122
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发表时间：
2017-04-01
期刊：
影响因子：
7.7
通讯作者：
Kim, Jae Bum
中科院分区：
文献类型：
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作者：
Huh, Jin Young;Park, Jeu;Kim, Jae Bum
脂肪组织炎症是肥胖的一个重要因素，它促进了胰岛素抵抗。在脂肪组织的各种细胞类型中，免疫细胞主动调节炎症反应，影响全身能量代谢。特别是，不变的自然杀伤T细胞(INKT)通过对抗肥胖引起的脂肪组织炎症，有助于缓解全身能量稳态的失调。然而，肥胖脂肪组织中脂肪iNKT细胞被激活并介导抗炎作用的分子机制尚不完全清楚。在目前的研究中，我们证明了脂肪细胞CD1d在刺激脂肪iNKT细胞，导致高脂饮食(HFD)喂养的小鼠的抗炎反应中起着关键作用。因此，脂肪细胞特异性CD1d基因敲除(CD1d(ADKO))小鼠的脂肪组织中iNKT细胞数量减少，对α-半乳糖神经酰胺诱导的iNKT细胞激活的反应减弱。此外，高脂饲料喂养的CD1d(ADKO)小鼠显示脂肪iNKT细胞中白介素4的表达减少，并加剧了脂肪组织炎症和胰岛素抵抗。总之，这些数据表明，脂肪细胞可以选择性地刺激脂肪iNKT细胞，以中介抗炎反应，并减弱肥胖脂肪组织中过度的促炎反应。
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(ADKO)) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to alpha-galactosylceramide-induced iNKT cell activation. Additionally, HFD-fed CD1d(ADKO) 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.