Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3-L1 cells

doi:10.1194/jlr.M200466-JLR200

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Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3-L1 cells

Soazig Le Lay, Céline Robichon, Xavier Le Liepvre, Georges Dagher, Pascal Ferré, and Isabelle Dugail

INSERM U465, Paris 75006

Corresponding Author: idugail{at}bhdc.jussieu.fr

Adipose cells are specialized in the storage of energy and contain large intracellular triglyceride-rich lipid droplets. They are also enriched with free cholesterol, and express sterol-regulated transcription factors such as LXR. Recently ABCA1 has been identified as a key protein controlling the release of cholesterol from peripheral cells. Moreover, the transcriptional control of ABCA1expression by LXR has been established. Here, using the 3T3-L1 adipose differentiation cell system, we addressed the question of the expression and function of ABCA1 in adipocytes. We observed that ABCA1 mRNA was strongly induced during adipose differentiation, but only limited variations (2 fold) were detected for ABCA1 protein. Accordingly, minor or no change were observed in phospholipid and cholesterol efflux between preadipocytes and adipocytes. This demonstrates that adipocytes differentially regulate ABCA1 mRNA and cholesterol efflux. We also found that, on a per cell basis, total cholesterol content remained stable during adipocyte differentiation of 3T3-L1 cells. However, cholesterol contents in membranes of differentiated cells were lower than those of preadipocytes, suggesting redistribution of cholesterol to the lipid droplet. Finally, we show that under standard isoproterenol-induced lipolytic stimulation, 3T3 L-1 adipocytes do not release cholesterol onto apoA-I. Long exposure to lipolytic agents (24 hours) was needed to detect an increased rate of apoA-I-mediated cholesterol efflux from fat cells. In conclusion, despite large induction of ABCA1 mRNA during differentiation, cholesterol efflux through the ABCA1 pathway remains limited in differentiated adipocytes. Moreover, stimulation of the ABCA1 pathway for cholesterol efflux from fat cells requires prolonged exposure to lipolytic agents. This is consistent with the view of the adipocyte behaving as a cholesterol sink, with plasma cholesterol-buffering properties.

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