Nutrition and Health Sciences, Department of


Date of this Version



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


Used by permission.


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 (ABCA1A/A) were

generated by crossing ABCA1floxed mice with aP2 cre transgenic mice. AT from ABCA1A/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 ABCA1A/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.