title: Myeloid cell-specific ABCA1 deletion does not worsen insulin resistance in HF diet-induced or genetically obese mouse models.
abstract: Obesity-associated low-grade chronic inflammation plays an important role in the development of insulin resistance. The membrane lipid transporter ATP-binding cassette transporter A1 (ABCA1) promotes formation of nascent HDL particles. ABCA1 also dampens macrophage inflammation by reducing cellular membrane cholesterol and lipid raft content. We tested the hypothesis that myeloid-specific ABCA1 deletion may exacerbate insulin resistance by increasing the obesity-associated chronic low-grade inflammation. Myeloid cell-specific ABCA1 knockout (MSKO) and wild-type (WT) mice developed obesity, insulin resistance, mild hypercholesterolemia, and hepatic steatosis to a similar extent with a 45% high-fat (HF) diet feeding or after crossing into the ob/ob background. Resident peritoneal macrophages and stromal vascular cells from obese MSKO mice accumulated significantly more cholesterol. Relative to chow, HF diet markedly induced macrophage infiltration and inflammatory cytokine expression to a similar extent in adipose tissue of WT and MSKO mice. Among pro-inflammatory cytokines examined, only IL-6 was highly upregulated in MSKO-ob/ob versus ob/ob mouse peritoneal macrophages, indicating a nonsignificant effect of myeloid ABCA1 deficiency on obesity-associated chronic inflammation. In conclusion, myeloid-specific ABCA1 deficiency does not exacerbate obesity-associated low-grade chronic inflammation and has minimal impact on the pathogenesis of insulin resistance in both HF diet-induced and genetically obese mouse models.
authors.affiliation: Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC; and.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Zhu
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
authors.forename: Xin
authors.initials: X
authors.lastname: Bi
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Chuang
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Brown
authors.forename: Mingxia
authors.initials: M
authors.lastname: Liu
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Seo
authors.forename: Helen
authors.initials: H
authors.lastname: Cuffe
authors.forename: Abraham K
authors.initials: AK
authors.lastname: Gebre
authors.forename: Elena
authors.initials: E
authors.lastname: Boudyguina
authors.forename: John S
authors.initials: JS
authors.lastname: Parks
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000172:deficiency / Q000235:genetics*; D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004822:Epididymis / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018925:Chemokines; D002784:Cholesterol; D018836:Inflammation Mediators; C577833:Abca1 protein, mouse
keywords: cholesterol; high-fat; inflammation; macrophage; obesity
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