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Nature:2型先天淋巴样细胞可促进脂肪米色化遏制肥胖

摘要 : 随着人类生活方式的西化,世界人口的肥胖率越来越高,而这一疾病通常由遗传因素和环境因素共同影响。最新研究表明包括单核细胞、粒细胞和淋巴细胞在内的免疫细胞参与了机体的稳态代谢平衡调控,但是在肥胖的个体中研究者们发现这些免疫细胞的功能出现了异常。

随着人类生活方式的西化,世界人口的肥胖率越来越高,而这一疾病通常由遗传因素和环境因素共同影响。最新研究表明包括单核细胞、粒细胞和淋巴细胞在内的免疫细胞参与了机体的稳态代谢平衡调控,但是在肥胖的个体中研究者们发现这些免疫细胞的功能出现了异常。

2型先天淋巴样细胞(ILC2s)能够调控获得性免疫反应以及嗜酸性粒细胞和可变激活巨噬细胞产生的免疫反应。近年来研究者们从小鼠的白色脂肪组织(WAT)中分离到2型先天淋巴样细胞,然而,在人类脂肪组织中并未鉴定出它们。小鼠脂肪组织中2型先天淋巴样细胞存在的作用可能是为了限制肥胖症状的发展。而且这类细胞通过何种作用机制来调控代谢稳态仍然是未解之谜。

在这篇研究论文中研究者们不仅在人类白色脂肪组织中鉴定出2型先天淋巴样细胞,还阐明了肥胖会引起人类和小鼠的白色脂肪组织中2型先天淋巴样细胞功能低下。白介素33对白色脂肪组织中2型先天淋巴样细胞的存活起到关键作用,而且能够通过增加卡路里消耗而限制小鼠肥胖发展。由于米色脂肪细胞高表达解耦联蛋白1,所以具有更强的消耗卡路里的能力。而白介素33处理小鼠后,白色脂肪组织中的脂肪细胞大量米色化,增加了小鼠整体的能量消耗。此外2型先天淋巴样细胞还能产生甲硫氨酸脑啡肽,这种肽能够直接作用于脂肪细胞使之产生更多的解耦联蛋白1,从而刺激白色脂肪细胞的米色化。

此研究最重要的发现在于是人们认识到除了响应感染和组织损坏等情况,2型先天淋巴样细胞还能够通过调控脂肪组织的功能来部分影响机体的代谢稳态。

原文标题:Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity

Jonathan R. Brestoff, Brian S. Kim, Steven A. Saenz, Rachel R. Stine, Laurel A. Monticelli, Gregory F. Sonnenberg, Joseph J. Thome, Donna L. Farber, Kabirullah Lutfy, Patrick Seale & David Artis

Obesity is an increasingly prevalent disease regulated by genetic and environmental factors. Emerging studies indicate that immune cells, including monocytes, granulocytes and lymphocytes, regulate metabolic homeostasis and are dysregulated in obesity. Group 2 innate lymphoid cells (ILC2s) can regulate adaptive immunity and eosinophil and alternatively activated macrophage responses, and were recently identified in murine white adipose tissue (WAT) wher they may act to limit the development of obesity. However, ILC2s have not been identified in human adipose tissue, and the mechanisms by which ILC2s regulate metabolic homeostasis remain unknown. Here we identify ILC2s in human WAT and demonstrate that decreased ILC2 responses in WAT are a conserved characteristic of obesity in humans and mice. Interleukin (IL)-33 was found to be critical for the maintenance of ILC2s in WAT and in limiting adiposity in mice by increasing caloric expenditure. This was associated with recruitment of uncoupling protein 1 (UCP1)+ beige adipocytes in WAT, a process known as beiging or browning that regulates caloric expenditure. IL-33-induced beiging was dependent on ILC2s, and IL-33 treatment or transfer of IL-33-elicited ILC2s was sufficient to drive beiging independently of the adaptive immune system, eosinophils or IL-4 receptor signalling. We found that ILC2s produce methionine-enkephalin peptides that can act directly on adipocytes to upregulate Ucp1 expression in vitro and that promote beiging in vivo. Collectively, these studies indicate that, in addition to responding to infection or tissue damage, ILC2s can regulate adipose function and metabolic homeostasis in part via production of enkephalin peptides that elicit beiging.

来源: Nature 浏览次数:83

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