Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S]
Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl-CoAs to FFAs. 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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520310099 |
| _version_ | 1824018929984471040 |
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| author | Valerie Z. Wall Shelley Barnhart Farah Kramer Jenny E. Kanter Anuradha Vivekanandan-Giri Subramaniam Pennathur Chiara Bolego Jessica M. Ellis Miguel A. Gijón Michael J. Wolfgang Karin E. Bornfeldt |
| author_facet | Valerie Z. Wall Shelley Barnhart Farah Kramer Jenny E. Kanter Anuradha Vivekanandan-Giri Subramaniam Pennathur Chiara Bolego Jessica M. Ellis Miguel A. Gijón Michael J. Wolfgang Karin E. Bornfeldt |
| author_sort | Valerie Z. Wall |
| collection | DOAJ |
| description | Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl-CoAs to FFAs. 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 WT and ACOT7-deficient macrophage lysates indicated that endogenous ACOT7 contributes a significant fraction of total acyl-CoA thioesterase activity toward C20:4-, C20:5-, and C22:6-CoA, but contributes little activity toward 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, although ACOT7 has preferential thioesterase activity toward these lipid species, loss of ACOT7 has no major detrimental effect on macrophage inflammatory phenotypes.≥ |
| first_indexed | 2024-12-19T01:13:33Z |
| format | Article |
| id | doaj.art-83f7d024471b48379c8e62abb1b69a7f |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T01:13:33Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-83f7d024471b48379c8e62abb1b69a7f2022-12-21T20:42:53ZengElsevierJournal of Lipid Research0022-22752017-06-0158611741185Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S]Valerie Z. Wall0Shelley Barnhart1Farah Kramer2Jenny E. Kanter3Anuradha Vivekanandan-Giri4Subramaniam Pennathur5Chiara Bolego6Jessica M. Ellis7Miguel A. Gijón8Michael J. Wolfgang9Karin E. Bornfeldt10Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WA; Division of Metabolism, Endocrinology and Nutrition, and Department of Pathology, UW Medicine Diabetes Institute, University of Washington, Seattle, WADepartment of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WADepartment of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WADepartment of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WADepartment of Internal Medicine, University of Michigan, Ann Arbor, MIDepartment of Internal Medicine, University of Michigan, Ann Arbor, MIDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, ItalyDepartment of Nutrition Science, Purdue University, West Lafayette, IN; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MDDepartment of Pharmacology, University of Colorado Denver, Aurora, CODepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MDTo whom correspondence should be addressed.; Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WA; Division of Metabolism, Endocrinology and Nutrition, and Department of Pathology, UW Medicine Diabetes Institute, University of Washington, Seattle, WAAcyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl-CoAs to FFAs. 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 WT and ACOT7-deficient macrophage lysates indicated that endogenous ACOT7 contributes a significant fraction of total acyl-CoA thioesterase activity toward C20:4-, C20:5-, and C22:6-CoA, but contributes little activity toward 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, although ACOT7 has preferential thioesterase activity toward these lipid species, loss of ACOT7 has no major detrimental effect on macrophage inflammatory phenotypes.≥http://www.sciencedirect.com/science/article/pii/S0022227520310099atherosclerosiscytokinesdiabetesfatty acidinflammationlipidomics |
| spellingShingle | Valerie Z. Wall Shelley Barnhart Farah Kramer Jenny E. Kanter Anuradha Vivekanandan-Giri Subramaniam Pennathur Chiara Bolego Jessica M. Ellis Miguel A. Gijón Michael J. Wolfgang Karin E. Bornfeldt Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S] Journal of Lipid Research atherosclerosis cytokines diabetes fatty acid inflammation lipidomics |
| title | Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S] |
| title_full | Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S] |
| title_fullStr | Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S] |
| title_full_unstemmed | Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S] |
| title_short | Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages[S] |
| title_sort | inflammatory stimuli induce acyl coa thioesterase 7 and remodeling of phospholipids containing unsaturated long ≥c20 acyl chains in macrophages s |
| topic | atherosclerosis cytokines diabetes fatty acid inflammation lipidomics |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520310099 |
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