Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis

12/15 lipoxygenase (12/15LO) oxidizes polyunsaturated fatty acids (PUFAs) to form bioactive lipid mediators. The role of 12/15LO in atherosclerosis development remains controversial. We evaluated atherosclerosis development and lipid metabolism in 12/15LO-LDL receptor (LDLr) double knockout (DK) vs....

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Main Authors: Shunxing Rong, Qiang Cao, Mingxia Liu, Jeongmin Seo, Lin Jia, Elena Boudyguina, Abraham K. Gebre, Perry L. Colvin, Thomas L. Smith, Robert C. Murphy, Nilamadhab Mishra, John S. Parks
Format: Article
Language:English
Published: Elsevier 2012-04-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520405620
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spelling doaj-e01e069bb0fa4b40be7d94acf82a97262021-04-28T07:15:07ZengElsevierJournal of Lipid Research0022-22752012-04-01534686695Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosisShunxing Rong0Qiang Cao1Mingxia Liu2Jeongmin Seo3Lin Jia4Elena Boudyguina5Abraham K. Gebre6Perry L. Colvin7Thomas L. Smith8Robert C. Murphy9Nilamadhab Mishra10John S. Parks11Department of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NCDepartment of Internal Medicine/Section on Rheumatology, Wake Forest School of Medicine, Winston-Salem, NCDepartment of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NCDepartment of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NCDepartment of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NCDepartment of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NCDepartment of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NCDivision of Geriatric Medicine and Gerontology, John Hopkins School of Medicine, Baltimore, MDDepartment of Orthopaedic Surgery, Wake Forest School of Medicine, Winston-Salem, NCDepartment of Pharmacology, University of Colorado-Denver, Aurora, CODepartment of Internal Medicine/Section on Rheumatology, Wake Forest School of Medicine, Winston-Salem, NCTo whom correspondence should be addressed; Department of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC12/15 lipoxygenase (12/15LO) oxidizes polyunsaturated fatty acids (PUFAs) to form bioactive lipid mediators. The role of 12/15LO in atherosclerosis development remains controversial. We evaluated atherosclerosis development and lipid metabolism in 12/15LO-LDL receptor (LDLr) double knockout (DK) vs. LDLr knockout (SK) mice fed a PUFA-enriched diet to enhance production of 12/15LO products. Compared with SK controls, DK mice fed a PUFA-enriched diet had decreased plasma and liver lipid levels, hepatic lipogenic gene expression, VLDL secretion, and aortic atherosclerosis and increased VLDL turnover. Bone marrow transplantation and Kupffer cell ablation studies suggested both circulating leukocytes and Kupffer cells contributed to the lipid phenotype in 12/15LO-deficient mice. Conditioned medium from in vitro incubation of DK vs. SK macrophages reduced triglyceride secretion in McArdle 7777 hepatoma cells. Our results suggest that, in the context of dietary PUFA enrichment, macrophage 12/15LO expression adversely affects plasma and hepatic lipid metabolism, resulting in exacerbated atherosclerosis.http://www.sciencedirect.com/science/article/pii/S0022227520405620bone marrow transplantationKupffer cellhepatosteatosisVLDL metabolism
collection DOAJ
language English
format Article
sources DOAJ
author Shunxing Rong
Qiang Cao
Mingxia Liu
Jeongmin Seo
Lin Jia
Elena Boudyguina
Abraham K. Gebre
Perry L. Colvin
Thomas L. Smith
Robert C. Murphy
Nilamadhab Mishra
John S. Parks
spellingShingle Shunxing Rong
Qiang Cao
Mingxia Liu
Jeongmin Seo
Lin Jia
Elena Boudyguina
Abraham K. Gebre
Perry L. Colvin
Thomas L. Smith
Robert C. Murphy
Nilamadhab Mishra
John S. Parks
Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
Journal of Lipid Research
bone marrow transplantation
Kupffer cell
hepatosteatosis
VLDL metabolism
author_facet Shunxing Rong
Qiang Cao
Mingxia Liu
Jeongmin Seo
Lin Jia
Elena Boudyguina
Abraham K. Gebre
Perry L. Colvin
Thomas L. Smith
Robert C. Murphy
Nilamadhab Mishra
John S. Parks
author_sort Shunxing Rong
title Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
title_short Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
title_full Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
title_fullStr Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
title_full_unstemmed Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
title_sort macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2012-04-01
description 12/15 lipoxygenase (12/15LO) oxidizes polyunsaturated fatty acids (PUFAs) to form bioactive lipid mediators. The role of 12/15LO in atherosclerosis development remains controversial. We evaluated atherosclerosis development and lipid metabolism in 12/15LO-LDL receptor (LDLr) double knockout (DK) vs. LDLr knockout (SK) mice fed a PUFA-enriched diet to enhance production of 12/15LO products. Compared with SK controls, DK mice fed a PUFA-enriched diet had decreased plasma and liver lipid levels, hepatic lipogenic gene expression, VLDL secretion, and aortic atherosclerosis and increased VLDL turnover. Bone marrow transplantation and Kupffer cell ablation studies suggested both circulating leukocytes and Kupffer cells contributed to the lipid phenotype in 12/15LO-deficient mice. Conditioned medium from in vitro incubation of DK vs. SK macrophages reduced triglyceride secretion in McArdle 7777 hepatoma cells. Our results suggest that, in the context of dietary PUFA enrichment, macrophage 12/15LO expression adversely affects plasma and hepatic lipid metabolism, resulting in exacerbated atherosclerosis.
topic bone marrow transplantation
Kupffer cell
hepatosteatosis
VLDL metabolism
url http://www.sciencedirect.com/science/article/pii/S0022227520405620
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