Lysophosphatidic Acid Induces Aerobic Glycolysis, Lipogenesis, and Increased Amino Acid Uptake in BV-2 Microglia

被引：13

作者：

Joshi, Lisha ^{[1
]}

Plastira, Ioanna ^{[1
]}

Bernhart, Eva ^{[1
]}

Reicher, Helga ^{[1
]}

Koyani, Chintan N. ^{[1
]}

Madl, Tobias ^{[1
,2
]}

Madreiter-Sokolowski, Corina ^{[1
]}

Koshenov, Zhanat ^{[1
]}

Graier, Wolfgang F. ^{[1
,2
]}

Hallstrom, Seth ^{[3
]}

Sattler, Wolfgang ^{[1
,2
]}

机构：

[1] Med Univ Graz, Gottfried Schatz Res Ctr, Div Mol Biol & Biochem, A-8010 Graz, Austria

[2] BioTechMed Graz, A-8010 Graz, Austria

[3] Med Univ Graz, Otto Loewi Res Ctr, Div Physiol Chem, A-8010 Graz, Austria

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 04期

基金：

奥地利科学基金会;

关键词：

ACC; aerobic glycolysis; Akt; fatty acids; Hif1α mTOR;

D O I：

10.3390/ijms22041968

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lysophosphatidic acid (LPA) species are a family of bioactive lipids that transmit signals via six cognate G protein-coupled receptors, which are required for brain development and function of the nervous system. LPA affects the function of all cell types in the brain and can display beneficial or detrimental effects on microglia function. During earlier studies we reported that LPA treatment of microglia induces polarization towards a neurotoxic phenotype. In the present study we investigated whether these alterations are accompanied by the induction of a specific immunometabolic phenotype in LPA-treated BV-2 microglia. In response to LPA (1 mu M) we observed slightly decreased mitochondrial respiration, increased lactate secretion and reduced ATP/ADP ratios indicating a switch towards aerobic glycolysis. Pathway analyses demonstrated induction of the Akt-mTOR-Hif1 alpha axis under normoxic conditions. LPA treatment resulted in dephosphorylation of AMP-activated kinase, de-repression of acetyl-CoA-carboxylase and increased fatty acid content in the phospholipid and triacylglycerol fraction of BV-2 microglia lipid extracts, indicating de novo lipogenesis. LPA led to increased intracellular amino acid content at one or more time points. Finally, we observed LPA-dependent generation of reactive oxygen species (ROS), phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), upregulated protein expression of the Nrf2 target regulatory subunit of glutamate-cysteine ligase and increased glutathione synthesis. Our observations suggest that LPA, as a bioactive lipid, induces subtle alterations of the immunometabolic program in BV-2 microglia.

引用

页码：1 / 26

页数：26

共 87 条

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