Myeloid cell-specific ABCA1 deletion does not worsen insulin resistance in HF dietinduced or genetically obese mouse models

Authors

Xuewei Zhu, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
Soonkyu Chung, University of Nebraska-LincolnFollow
Xin Bi, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
Chia-Chi Chuang, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
Amanda L. Brown, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC;
Mingxia Liu, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
Jeongmin Seo, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
Helen Cuffe, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
Abraham K. Gebre, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
Elena Boudyguina, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NC
John S. Parks, Department of Pathology/Lipid Sciences and Wake Forest School of Medicine, Winston-Salem, NCFollow

Document Type

Article

Date of this Version

2013

Citation

J Lipid Res. 2013 Oct; 54(10): 2708–2717.

Comments

Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc. Used by permission.

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 proinflammatory 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.