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

Xuewei Zhu, Soonkyu Chung, Xin Bi, Chia Chi Chuang, Amanda L. Brown, Mingxia Liu, Jeongmin Seo, Helen Cuffe, Abraham K. Gebre, Elena Boudyguina, John S. Parks

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 myeloidspecific 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.

Original languageEnglish (US)
Pages (from-to)2708-2717
Number of pages10
JournalJournal of Lipid Research
Volume54
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • Cholesterol
  • High-fat
  • Inflammation
  • Macrophage
  • Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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