Department of Medicine (H7), Karolinska University Hospital , Stockholm, Sweden.
CHU Clermont-Ferrand, Service D'endocrinologie, Diabétologie et Maladies Métaboliques , Clermont-Ferrand, France.
Adipocyte. 2020 Dec;9(1):620-625. doi: 10.1080/21623945.2020.1831825.
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.
白色脂肪组织（WAT）的慢性低度炎症是肥胖的标志之一，据推测它有助于导致胰岛素抵抗和 2 型糖尿病。尽管如此，WAT 炎症的潜在因果机制仍不清楚。基于对人体 WAT 的代谢组学分析，Petrus 等人表明，在肥胖状态下，氨基酸谷氨酰胺是最明显减少的极性代谢物。脂肪细胞中谷氨酰胺水平的降低通过诱导糖酵解和己糖胺生物合成途径诱导尿苷二磷酸 N-乙酰葡萄糖胺（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，体外和体内补充谷氨酰胺可逆转这些作用。总之，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一种表观遗传联系。这篇评论讨论了这些发现及其在胰岛素抵抗和 2 型糖尿病方面的可能治疗相关性。
