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Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-12-12 , DOI: 10.1016/j.cmet.2019.11.019 Paul Petrus 1 , Simon Lecoutre 1 , Lucile Dollet 2 , Clotilde Wiel 3 , André Sulen 4 , Hui Gao 1 , Beatriz Tavira 1 , Jurga Laurencikiene 1 , Olav Rooyackers 5 , Antonio Checa 6 , Iyadh Douagi 1 , Craig E Wheelock 6 , Peter Arner 1 , Mark McCarthy 7 , Martin O Bergo 3 , Laurienne Edgar 8 , Robin P Choudhury 8 , Myriam Aouadi 4 , Anna Krook 2 , Mikael Rydén 1
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-12-12 , DOI: 10.1016/j.cmet.2019.11.019 Paul Petrus 1 , Simon Lecoutre 1 , Lucile Dollet 2 , Clotilde Wiel 3 , André Sulen 4 , Hui Gao 1 , Beatriz Tavira 1 , Jurga Laurencikiene 1 , Olav Rooyackers 5 , Antonio Checa 6 , Iyadh Douagi 1 , Craig E Wheelock 6 , Peter Arner 1 , Mark McCarthy 7 , Martin O Bergo 3 , Laurienne Edgar 8 , Robin P Choudhury 8 , Myriam Aouadi 4 , Anna Krook 2 , Mikael Rydén 1
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While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear. We hypothesized that the local metabolic environment could be an important determinant. To this end, we compared metabolites released from WAT of 81 obese and non-obese women. This identified glutamine to be downregulated in obesity and inversely associated with a pernicious WAT phenotype. Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT. Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels. UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase. Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response. Altogether, glutamine metabolism is linked to WAT inflammation in obesity.
中文翻译：
谷氨酰胺将肥胖与人类白色脂肪组织中的炎症联系起来。
虽然肥胖症和相关的代谢并发症与白色脂肪组织（WAT）的炎症有关，但其致病因素仍不清楚。我们假设当地的代谢环境可能是一个重要的决定因素。为此，我们比较了81位肥胖和非肥胖妇女从WAT释放的代谢物。这表明谷氨酰胺在肥胖中被下调并且与有害的WAT表型成反比。谷氨酰胺的体外和体内给药均能减弱脂肪细胞中的促炎基因和蛋白水平以及WAT中的WAT和巨噬细胞浸润。对人体脂肪细胞的代谢组学和生物能分析表明，谷氨酰胺减弱了糖酵解作用，降低了尿苷二磷酸N-乙酰氨基葡萄糖（UDP-GlcNAc）的水平。UDP-GlcNAc是由O-GlcNAc转移酶介导的翻译后修饰O-连接的β-N-乙酰氨基葡萄糖（O-GlcNAc）的底物。在人体脂肪细胞中进行的功能性研究建立了减少的谷氨酰胺，核蛋白的O-GlcNAcylation和促炎性转录反应之间的机制联系。总之，谷氨酰胺代谢与肥胖中的WAT炎症有关。
更新日期：2019-12-19
中文翻译：
谷氨酰胺将肥胖与人类白色脂肪组织中的炎症联系起来。
虽然肥胖症和相关的代谢并发症与白色脂肪组织（WAT）的炎症有关，但其致病因素仍不清楚。我们假设当地的代谢环境可能是一个重要的决定因素。为此，我们比较了81位肥胖和非肥胖妇女从WAT释放的代谢物。这表明谷氨酰胺在肥胖中被下调并且与有害的WAT表型成反比。谷氨酰胺的体外和体内给药均能减弱脂肪细胞中的促炎基因和蛋白水平以及WAT中的WAT和巨噬细胞浸润。对人体脂肪细胞的代谢组学和生物能分析表明，谷氨酰胺减弱了糖酵解作用，降低了尿苷二磷酸N-乙酰氨基葡萄糖（UDP-GlcNAc）的水平。UDP-GlcNAc是由O-GlcNAc转移酶介导的翻译后修饰O-连接的β-N-乙酰氨基葡萄糖（O-GlcNAc）的底物。在人体脂肪细胞中进行的功能性研究建立了减少的谷氨酰胺，核蛋白的O-GlcNAcylation和促炎性转录反应之间的机制联系。总之，谷氨酰胺代谢与肥胖中的WAT炎症有关。
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