Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.
Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.
复制标题
脂肪细胞衍生的犬尿氨酸通过激活 AhR/STAT3/IL-6 信号传导促进肥胖和胰岛素抵抗
DOI：
10.1038/s41467-022-31126-5
复制
发表时间：
2022-06-17
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
氨基酸代谢异常是肥胖的常见现象。特别是，肥胖患者的特点是血浆中犬尿氨酸（Kyn）过高。然而，Kyn的主要来源及其对代谢综合征的影响尚未得到充分解决。本研究表明，脂肪细胞中过量表达的吲哚胺2,3-双加氧酶1 （IDO1）主要导致Kyn过量，表明脂肪细胞在Kyn代谢中起核心作用。脂肪细胞中Ido1的消耗消除了Kyn的积累，保护小鼠免受肥胖。从机制上讲，Kyn通过激活芳烃受体(AhR)/信号转导器和转录3 /白细胞介素-6信号转导激活剂来损害脂肪细胞的脂质稳态。脂肪细胞AhR的基因消融可消除Kyn的作用。此外，补充维生素B6可改善Kyn积累，保护小鼠免于肥胖。总的来说，我们的数据支持脂肪细胞是增加循环Kyn的主要来源，而消除积累的Kyn可能是对抗肥胖的可行策略。犬尿氨酸，一种色氨酸代谢物，在肥胖个体的循环血浆中增加，但其来源尚不清楚。在这里，作者在老鼠身上展示了成熟的脂肪细胞产生犬尿氨酸，维生素B6可以防止积累并防止高脂肪饮食。
Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity. Kynurenine, a tryptophan metabolite, is increased in the circulating plasma of obese individuals, but the source has been unclear. Here, the authors show in mice that mature adipocytes produce kynurenine, with vitamin B6 administration preventing accumulation and protecting against high-fat diet.
登录
查看更多内容
小肠保护肝脏免受果糖引起的脂肪变性。
影响因子：
20.8
作者：
Jang C;Wada S;Yang S;Gosis B;Zeng X;Zhang Z;Shen Y;Lee G;Arany Z;Rabinowitz JD
通讯作者：
Rabinowitz JD
影响因子：
16.8
作者：
Munn DH;Mellor AL
通讯作者：
Mellor AL
影响因子：
6.9
作者：
Favennec, Marie;Hennart, Benjamin;Poulain-Godefroy, Odile
通讯作者：
Poulain-Godefroy, Odile
影响因子：
5.8
作者：
Loeb, Stefan;Koenigsrainer, Alfred;Terness, Peter
通讯作者：
Terness, Peter
DOI：
10.1073/pnas.1920004117
发表时间：
2020-02-11
影响因子：
11.1
作者：
Han, Myoung Sook;White, Alexis;Davis, Roger J.
通讯作者：
Davis, Roger J.