TY - JOUR T1 - Lipin-1 regulates lipid catabolism in pro-resolving macrophages JF - bioRxiv DO - 10.1101/2020.06.03.121293 SP - 2020.06.03.121293 AU - Robert M. Schilke AU - Cassidy M.R. Blackburn AU - Shashanka Rao AU - David Krzywanski AU - Brian N. Finck AU - Matthew D. Woolard Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/03/2020.06.03.121293.abstract N2 - Macrophages reprogram their metabolism to promote appropriate responses. Pro-resolving macrophages primarily utilize 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 is not fully elucidated. In this current study we show that lipin-1, a phosphatidic acid phosphatase and regulator of lipid metabolism, is required for increased oxidative phosphorylation during IL-4 mediated responses. 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 derived lipids. BMDMs 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 intermediary metabolism within pro-resolving macrophages and highlights the importance of aligning macrophage metabolism with proper responses to stimuli.Competing Interest StatementThe authors have declared no competing interest. ER -