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Glutamine metabolism in adipocytes: a bona fide epigenetic modulator of inflammation
Adipocyte ( IF 3.5 ) Pub Date : 2020-10-12 , DOI: 10.1080/21623945.2020.1831825
Simon Lecoutre 1 , Salwan Maqdasy 1, 2, 3 , Paul Petrus 4 , Alison Ludzki 1 , Morgane Couchet 1 , Niklas Mejhert 1 , Mikael Rydén 1
Affiliation  

ABSTRACT

A chronic low-grade inflammation of white adipose tissue (WAT) is one of the hallmarks of obesity and is proposed to contribute to insulin resistance and type 2 diabetes. Despite this, the causal mechanisms underlying WAT inflammation remain unclear. Based on metabolomic analyses of human WAT, Petrus et al. showed that the amino acid glutamine was the most markedly reduced polar metabolite in the obese state. Reduced glutamine levels in adipocytes induce an increase of Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels via induction of glycolysis and the hexosamine biosynthetic pathways. This promotes nuclear O-GlcNAcylation, a posttranslational modification that activates the transcription of pro-inflammatory genes. Conversely, glutamine supplementation in vitro and in vivo, reversed these effects. Altogether, dysregulation of intracellular glutamine metabolism in WAT establishes an epigenetic link between adipocytes and inflammation. This commentary discusses these findings and their possibly therapeutic relevance in relation to insulin resistance and type 2 diabetes.



中文翻译:

脂肪细胞中的谷氨酰胺代谢:真正的炎症表观遗传调节剂

摘要

白色脂肪组织(WAT)的慢性低度炎症是肥胖症的标志之一,被认为有助于胰岛素抵抗和2型糖尿病。尽管如此,WAT炎症的病因机制仍不清楚。根据人类WAT的代谢组学分析,Petrus等人。结果表明,氨基酸谷氨酰胺是肥胖状态下还原性最强的代谢产物。脂肪细胞中谷氨酰胺水平的降低通过糖酵解和己糖胺生物合成途径的诱导而导致尿苷二磷酸N-乙酰氨基葡萄糖(UDP-GlcNAc)水平的增加。这促进了核O-GlcNAcylation,这是一种翻译后修饰,可激活促炎基因的转录。相反,在体外和体内补充谷氨酰胺逆转了这些作用。共,WAT中细胞内谷氨酰胺代谢的失调在脂肪细胞和炎症之间建立了表观遗传学联系。这篇评论讨论了这些发现以及与胰岛素抵抗和2型糖尿病有关的治疗意义。

更新日期:2020-10-12
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