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

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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, Rooyackers, Olav, Checa, Antonio, Douagi, Iyadh, Wheelock, Craig E., Arner, Peter, McCarthy, Mark, Bergo, Martin O., Edgar, Laurienne, Choudhury, Robin P., Aouadi, Myriam, Krook, Anna, Rydén, Mikael·2020·Cell Metabolism

DOI 10.1016/j.cmet.2019.11.019

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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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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
ORCID: Petrus, Paul
Lecoutre, Simon
Dollet, Lucile
Wiel, Clotilde
Sulen, André
Gao, Hui
Tavira, Beatriz
Laurencikiene, Jurga
Rooyackers, Olav
Checa, Antonio
Douagi, Iyadh
Wheelock, Craig E.
Arner, Peter
McCarthy, Mark
Edgar, Laurienne
Choudhury, Robin P.
Aouadi, Myriam
Krook, Anna
Rydén, Mikael
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2020-02
Volume: 31
Issue: 2
Pages: 375-390.e11
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2019.11.019
OpenAlex: W2996614832
Cited by: 254
References: 72
Citations by year: 2026: 26 · 2025: 55 · 2024: 41 · 2023: 46 · 2022: 38 · 2021: 20 · 2020: 25
FWCI: 15.79
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
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 › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › 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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Glutamine Links Obesity to Inflammation in Human White Adipose Tissue

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