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Glutamine Links Obesity to Inflammation in Human White Adipose Tissue
Open accessAbstract
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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“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]
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“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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Metadata
- 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
- 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
- FWCI
- 15.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- 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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