Elsevier

Advances in Nutrition

Volume 10, Issue 2, March 2019, Pages 321-330
Advances in Nutrition

Glutamine Metabolism in Macrophages: A Novel Target for Obesity/Type 2 Diabetes

https://doi.org/10.1093/advances/nmy084Get rights and content
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ABSTRACT

Obesity is a nutritional disorder resulting from a chronic imbalance between energy intake and expenditure. This disease is characterized by inflammation in multiple cell types, including macrophages. M1 macrophage responses are correlated with the progression of obesity or diabetes; therefore, strategies that induce repolarization of macrophages from an M1 to an M2 phenotype may be promising for the prevention of obesity- or diabetes-associated pathology. Glutamine (the most abundant amino acid in the plasma of humans and many other mammals including rats) is effective in inducing polarization of M2 macrophages through the glutamine–UDP-N-acetylglucosamine pathway and α-ketoglutarate produced via glutaminolysis, whereas succinate synthesized via glutamine-dependent anerplerosis or the γ-aminobutyric acid shunt promotes polarization of M1 macrophages. Interestingly, patients with obesity or diabetes show altered glutamine metabolism, including decreases in glutamine and α-ketoglutarate concentrations in serum but increases in succinate concentrations. Thus, manipulation of macrophage polarization through glutamine metabolism may provide a potential target for prevention of obesity- or diabetes-associated pathology.

α-ketoglutarate
diabetes
glutamine
obesity
macrophages
succinate

Abbreviations used

BMDM
bone-marrow–derived macrophage
CCL2
chemokine (C-C motif) ligand 2
FAO
fatty acid oxidation
GABA
γ-aminobutyric acid
GlcNAc
N-acetylglucosamine
GPR91
G protein–coupled receptor 91
GS
glutamine synthetase
HIF
hypoxia inducible factor
IKK
inhibitor of NF-κB kinase
IRF
interferon regulatory factor
OXPHOS
oxidative phosphorylation
PPP
pentose phosphate pathway
TCA
tricarboxylic acid
Th
T-helper

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Supported by National Natural Science Foundation of China grants 31872365 (to WR) and 31790411 (to JD) and “Innovation Platform and Talents Program” of Hunan Provincial Science and Technology Department grant 2018RS3105 (to YY).

Author disclosures: WR, YX, SC, GW, FWB, BZ, BT, GZ, JD, and YY, no conflicts of interest.