Macrophage-Associated Lipin-1 Promotes β-Oxidation in Response to Proresolving Stimuli.
Robert M SchilkeCassidy M R BlackburnShashanka RaoDavid M KrzywanskiBrian N FinckMatthew D WoolardPublished in: ImmunoHorizons (2020)
Macrophages reprogram their metabolism to promote appropriate responses. Proresolving macrophages primarily use fatty acid oxidation as an energy source. Metabolites generated during the catabolism of fatty acids aid in the resolution of inflammation and tissue repair, but the regulatory mechanisms that control lipid metabolism in macrophages are not fully elucidated. Lipin-1, a phosphatidic acid phosphatase that has transcriptional coregulator activity, regulates lipid metabolism in a variety of cells. In this current study, we show that lipin-1 is required for increased oxidative phosphorylation in IL-4 stimulated mouse (Mus musculus) macrophages. We also show that the transcriptional coregulatory function of lipin-1 is required for β-oxidation in response to palmitate (free fatty acid) and apoptotic cell (human) stimulation. Mouse bone marrow-derived macrophages lacking lipin-1 have a reduction in critical TCA cycle metabolites following IL-4 stimulation, suggesting a break in the TCA cycle that is supportive of lipid synthesis rather than lipid catabolism. Together, our data demonstrate that lipin-1 regulates cellular metabolism in macrophages in response to proresolving stimuli and highlights the importance of aligning macrophage metabolism with macrophage phenotype.
Keyphrases
- fatty acid
- transcription factor
- adipose tissue
- gene expression
- endothelial cells
- ms ms
- oxidative stress
- induced apoptosis
- stem cells
- mesenchymal stem cells
- machine learning
- signaling pathway
- big data
- artificial intelligence
- electron transfer
- endoplasmic reticulum stress
- cell cycle arrest
- pi k akt
- heat stress
- protein kinase