Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130.
Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA 71130; and.
Immunohorizons. 2020 Oct 19;4(10):659-669. doi: 10.4049/immunohorizons.2000047.
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 () 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.
巨噬细胞重新编程其代谢以促进适当的反应。促修复巨噬细胞主要将脂肪酸氧化作为能量来源。脂肪酸分解代谢过程中产生的代谢物有助于炎症的消退和组织修复，但控制巨噬细胞中脂质代谢的调节机制尚未完全阐明。脂磷酶 1 是一种具有转录共激活剂活性的磷酸脂酶，可调节多种细胞中的脂质代谢。在本研究中，我们表明脂磷酶 1 是 IL-4 刺激的小鼠巨噬细胞中氧化磷酸化增加所必需的。我们还表明，脂磷酶 1 的转录共激活剂功能对于对棕榈酸（游离脂肪酸）和凋亡细胞（人）刺激的β氧化是必需的。缺乏脂磷酶 1 的小鼠骨髓来源的巨噬细胞在受到 IL-4 刺激后，三羧酸 (TCA) 循环的关键代谢物减少，这表明 TCA 循环中断，有利于脂质合成而不是脂质分解。总之，我们的数据表明脂磷酶 1 可调节巨噬细胞对促修复刺激的细胞代谢，并强调了使巨噬细胞代谢与巨噬细胞表型相协调的重要性。
