Journal of Lipid Research
Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl-CoAs to free fatty acids. ACOT7 is induced by lipopolysaccharide (LPS), thus we investigated downstream effects of LPS-induced induction of ACOT7 and its role in inflammatory settings in myeloid cells. Enzymatic thioesterase activity assays in wildtype and ACOT7-deficient macrophage lysates indicated that endogenous ACOT7 contributes a significant fraction of total acyl-CoA thioesterase activity towards C20:4-CoA, C20:5-CoA and C22:6-CoA, but contributes little activity towards shorter acyl-CoA species. Lipidomic analyses revealed that LPS causes a dramatic increase primarily in bis(monoacylglycero)phosphate species containing long (C20) polyunsaturated acyl-chains in macrophages, and that the limited effect observed by ACOT7-deficiency is restricted to glycerophospholipids containing 20-carbon unsaturated acyl-chains. Furthermore, ACOT7-deficiency did not detectably alter the ability of LPS to induce cytokines or prostaglandin E2 production in macrophages. Consistently, although ACOT7 was induced in macrophages from diabetic mice, hematopoietic ACOT7-deficiency did not alter the stimulatory effect of diabetes on systemic inflammation or atherosclerosis in LDL receptor-deficient mice. Thus, inflammatory stimuli induce ACOT7 and remodeling of phospholipids containing unsaturated long (C20)-acyl chains in macrophages, and though ACOT7 has preferential thioesterase activity toward these lipid species, loss of ACOT7 has no major detrimental effect on macrophage inflammatory phenotypes.