Cited by 261Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Glutamine Links Obesity to Inflammation in Human White Adipose Tissue

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Petrus, Paul, Lecoutre, Simon, Dollet, Lucile, Wiel, Clotilde, Sulen, André, Gao, Hui, Tavira, Beatriz, Laurencikiene, Jurga +12 more·2020·Cell Metabolism

Abstract

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.

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Crossref · 10.1016/j.cmet.2019.11.019

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  • Glutamine metabolism is linked to white adipose tissue inflammation in obesity.

    “Recently, glutamine metabolism has been shown to be linked to white adipose tissue (WAT) inflammation in obesity110.”

    From Glutamine reliance in cell metabolism (2020) · cites this paper as [110]

  • In the obese state, glutamine metabolism is impaired, leading to increased chromatin O-GlcNAcylation and activation of genes in proinflammatory pathways.

    “The researchers discovered that glutamine metabolism is impaired in the obese state, leading to increased chromatin O-GlcNAcylation and activation of genes in proinflammatory pathways.”

    From Glutamine reliance in cell metabolism (2020) · cites this paper as [110]

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Authors
Petrus, P., Lecoutre, S., Dollet, L., Wiel, C., Sulen, A., Gao, H., Tavira, B., Laurencikiene, J., Rooyackers, O., Checa, A., Douagi, I., Wheelock, C. E., Arner, P., McCarthy, M., Bergo, M. O., Edgar, L., Choudhury, R. P., Aouadi, M., Krook, A., & Rydén, M.
Affiliations
  • Karolinska Institutet (SE)
  • Karolinska University Hospital (SE)
  • Centre for Human Genetics (GB)
  • University of Oxford (GB)
Corresponding author
Rydén, Mikael
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2020-02
Volume
31
Issue
2
Pages
375-390.e11
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2996614832
Cited by
254
References
72
Citations by year
2026: 26 · 2025: 55 · 2024: 41 · 2023: 46 · 2022: 38 · 2021: 20 · 2020: 25 · 2014: 1
FWCI
15.79
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Knut och Alice Wallenbergs Stiftelse (2018.0094)
  • Vetenskapsrådet
  • Novo Nordisk Fonden (NNF15SA0018346, NNF15CC0018486)
  • European Foundation for the Study of Diabetes
  • Karolinska Institutet
  • Diabetesförbundet
  • Diabetes Research and Wellness Foundation
  • Stockholms Läns Landsting
  • Center for Innovative Medicine
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
glutamine, obesity, white adipose tissue inflammation, adipocytes, UDP-GlcNAc, O-GlcNAc transferase, O-GlcNAcylation, glycolysis, macrophage infiltration, pro-inflammatory gene expression
MeSH terms
Acetylglucosamine, Adult, Animals, Cells, Cultured, Female, Glucose, Glutamine, Glycosylation, Humans, Inflammation, Male, Mice, Inbred C57BL, Middle Aged, Obesity, Cohort Studies, N-Acetylglucosaminyltransferases, Adipocytes, Adipose Tissue, White

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