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Mini-Review

Glutamine metabolism in adipocytes: a bona fide epigenetic modulator of inflammation

, , , , , & show all
Pages 620-625 | Received 07 Jul 2020, Accepted 29 Sep 2020, Published online: 12 Oct 2020
 

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.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Diabetesfonden; Knut och Alice Wallenbergs Stiftelse; Novo Nordisk Fonden; Stockholms Läns Landsting; Vetenskapsrådet.