CD8+ T cells in beige adipogenesis and energy homeostasis
CD8+ T cells in beige adipogenesis and energy homeostasis
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DOI：
10.1172/jci.insight.95456
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发表时间：
2018-03-08
期刊：
影响因子：
8
通讯作者：
Karalis, Katia P.
中科院分区：
文献类型：
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作者：
Moysidou, Maria;Karaliota, Sevasti;Karalis, Katia P.
尽管肥胖患者白色脂肪组织（WAT）中淋巴细胞的积累与胰岛素抵抗有关，但淋巴细胞是否也参与WAT中能量稳态的调节尚不清楚。在这里，我们证明Rag1（-/-）小鼠的能量耗散增强，皮下WAT的儿茶酚胺输入增加，以及显著的米色脂肪形成。过继转移实验表明，CD8(+) T细胞缺乏是Rag1（-/-）小鼠米色脂肪生成增强的原因。一致地，我们发现CD8（-/-）小鼠也表现出增强的米色脂肪生成。综上所述，我们的研究结果确定了CD8(+) T细胞在ifn - γ介导的瘦WAT中调节能量耗散的作用。调节常驻免疫细胞的丰度和局部儿茶酚胺能活性。我们的研究结果为以CD8(+) T细胞丰度改变为特征的疾病中代谢功能障碍的临床症状提供了一个合理的解释，并表明靶向CD8(+) T细胞是治疗肥胖和其他能量稳态改变疾病的一种有希望的治疗方法。
Although accumulation of lymphocytes in the white adipose tissue (WAT) in obesity is linked to insulin resistance, it remains unclear whether lymphocytes also participate in the regulation of energy homeostasis in the WAT. Here, we demonstrate enhanced energy dissipation in Rag1(-/-) mice, increased catecholaminergic input to subcutaneous WAT, and significant beige adipogenesis. Adoptive transfer experiments demonstrated that CD8(+) T cell deficiency accounts for the enhanced beige adipogenesis in Rag1(-/-) mice. Consistently, we identified that CD8(-/-) mice also presented with enhanced beige adipogenesis. The inhibitory effect of CD8+ T cells on beige adipogenesis was reversed by blockade of IFN-gamma All together, our findings identify an effect of CD8(+) T cells in regulating energy dissipation in lean WAT, mediated by IFN-gamma. modulation of the abundance of resident immune cells and of local catecholaminergic activity. Our results provide a plausible explanation for the clinical signs of metabolic dysfunction in diseases characterized by altered CD8(+) T cell abundance and suggest targeting of CD8(+) T cells as a promising therapeutic approach for obesity and other diseases with altered energy homeostasis.