Adipose tissue ABCA1 contributes to HDL biogenesis in vivo

Authors

Soonkyu Chung, Department of Food Science and Human Nutrition, University of FloridaFollow
Janet K. Sawyer, Department of Pathology/Section on Lipid Sciences, Wake Forest School of MedicineFollow
Abraham K. Gebre, Department of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston- Salem, NC
Nobuyo Maeba, Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC
John S. Parks, Department of Pathology/Section on Lipid Sciences, Wake Forest School of Medicine, Winston- Salem, NC

Document Type

Article

Date of this Version

2011

Citation

Circulation. 2011 October 11; 124(15): 1663–1672.

Comments

Used by permission.

Abstract

Background—Adipose tissue (AT) is the body’s largest free cholesterol (FC) reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), a key cholesterol transporter for HDL biogenesis. However, the extent to which AT ABCA1 expression contributes to HDL biogenesis in vivo is unknown.

Methods and Results—Adipocyte-specific ABCA1 knockout mice (ABCA1^−A/−A) were

generated by crossing ABCA1floxed mice with aP2 cre transgenic mice. AT from ABCA1^−A/−A mice had −^A/−A mice had a twofold increase in FC content, compared to WT mice, and failed to efflux cholesterol to apoA-I.

However, cholesterol efflux from AT to plasma HDL was similar for both genotypes of mice.

Incubation of WT AT explants with apoA-I resulted in formation of multiple discrete-sized

nascent HDL particles ranging in diameter from 7.1–12 nm; similar incubations with ABCA1^−A/−A AT explants resulted in nascent HDL ¹²⁵I-HDL tracer was similar in both genotypes of recipient mice, suggesting that adipocyte ABCA1 deficiency reduces plasma HDL concentrations solely by reducing nascent HDL particle formation.

Conclusions—We provide in vivo evidence that AT ABCA1-dependent cholesterol efflux and nascent HDL particle formation contribute to systemic HDL biogenesis and that AT ABCA1 expression plays an important role in adipocyte cholesterol homeostasis.