High density lipoprotein-mediated cholesterol uptake and targeting to lipid droplets in adipocytes

Georges Dagher, Nathalie Donne, Christophe Klein, Pascal Ferré, and Isabelle Dugail

INSERM U465, Paris 75006

Corresponding Author: dagher{at}ccr.jussieu.fr

Adipocytes handle large quantities of free cholesterol in their cytoplasmic triglyceride lipid droplet. They also have a limited capability for endogenous cholesterol synthesis, and express high levels of the HDL receptor SR-BI, in a differentiation dependent manner. Given these unique characteristics of fat cells, we have analyzed the routes of HDL cholesterol trafficking at different phases of adipocyte differentiation in the 3T3 L1 cell line. One novel and salient feature of this paper is the observation of a widespread distribution in the cell cytoplasm of Golgi markers, caveolin 2 and NBD-cholesterol observed in the early phases of adipocyte formation, clearly distinct from that observed in mature fat cells (i.e with fully formed lipid vesicles).Thus in cells without visible lipid droplets, Golgi markers (Golgi 58K, golgin 97, TGN 38, rab 6 and bodipy-ceramide), caveolin2 and NBD-cholesterol all colocalize in a widespread distribution in the cell. In contrast, when lipid droplets are fully formed at latter stages, these markers clearly distributed to distinct cell compartments : a compact juxtanuclear structure for the Golgi markers and caveolin 2, while NDB cholesterol concentrates for a large part in lipid droplets. In addition, disorganization of the Golgi using three different agents (Brefeldin, monensin and N-Ethyl-Maleimide) drastically reduces NBD-Cholesterol uptake at different phases of adipocyte formation, strongly suggesting that an intact Golgi apparatus is required for HDL mediated NBD-uptake and routing and plays a critical role in these phenomenon.

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