瑞典卡罗林斯卡医学院Mikael Rydén课题组的最新研究发现，在肥胖患者中，谷氨酰胺与人类白色脂肪组织的炎症有关。相关论文在线发表在2019年12月19日出版的《细胞,—代谢》杂志上。

研究人员提出一下猜想：细胞所处代谢环境可能是导致肥胖的一个重要决定因素。为了验证此猜想，研究人员比较了81名肥胖和非肥胖妇女白色脂肪组织（WAT）释放的代谢物。研究发现谷氨酰胺在肥胖人群中下调并且与恶性WAT表型负相关。体内和体外实验都表明，谷氨酰胺降低了脂肪细胞和WAT中促炎基因的转录和蛋白水平以及WAT中巨噬细胞的浸润。

人脂肪细胞的代谢组学和生物功能分析表明，谷氨酰胺减弱了糖酵解作用，降低了尿苷二磷酸N-乙酰葡糖胺（UDP-GlcNAc）的水平。 UDP-GlcNAc是O-连接β-N-乙酰葡萄胺（O-GlcNAc）的翻译后修饰的底物，O-GlcNAc转移酶介导该反应。在人脂肪细胞中进行的功能性研究实验将谷氨酰胺的减少、核蛋白的O-GlcNAcy化和促炎性转录反应联系起来。该研究揭示了谷氨酰胺代谢与肥胖患者中WAT炎症有关。

据了解，虽然肥胖和相关的代谢并发症与白色脂肪组织的炎症有关，但仍不清楚其致病因素。

附：英文原文

Title: Glutamine Links Obesity to Inflammation in Human White Adipose Tissue

Author: Paul Petrus, Simon Lecoutre, Lucile Dollet, Clotilde Wiel, André Sulen, Hui Gao, Beatriz Tavira, Jurga Laurencikiene, Olav Rooyackers, Antonio Checa, Iyadh Douagi, Craig E. Wheelock, Peter Arner, Mark McCarthy, Martin O. Bergo, Laurienne Edgar, Robin P. Choudhury, Myriam Aouadi, Anna Krook, Mikael Rydén

Issue&Volume: December 19, 2019

Abstract: While obesity and associated metabolic complications are linked to inflammation ofwhite adipose tissue (WAT), the causal factors remain unclear. We hypothesized thatthe local metabolic environment could be an important determinant. To this end, wecompared metabolites released from WAT of 81 obese and non-obese women. This identifiedglutamine to be downregulated in obesity and inversely associated with a perniciousWAT phenotype. Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT andmacrophage infiltration in WAT. Metabolomic and bioenergetic analyses in human adipocytessuggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine(UDP-GlcNAc) levels. UDP-GlcNAc is the substrate for the post-translational modificationO-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.Functional studies in human adipocytes established a mechanistic link between reducedglutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptionalresponse. Altogether, glutamine metabolism is linked to WAT inflammation in obesity.

DOI: 10.1016/j.cmet.2019.11.019

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30663-1