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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1945.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Cytosolic Lipid Droplets Increase in Size by Microtubule-Dependent Complex Formation

Pontus Boström; Mikael Rutberg; Johanna Ericsson; Peter Holmdahl; Linda Andersson; Michael A. Frohman; Jan Borén; Sven-Olof Olofsson

From the Wallenberg Laboratory for Cardiovascular Research (P.B., M.R., J.E., L.A., J.B., S.-O.O.), Göteborg University, Sahlgrenska University Hospital and Holmdahl Biotech (P.H.), Göteborg, Sweden; and the Department of Pharmacological Science and the Center for Developmental Genetics (M.A.F.), Stony Brook University, Stony Brook, NY.

Correspondence to Sven-Olof Olofsson, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. E-mail Sven-Olof.Olofsson{at}wlab.gu.se

Objectives— Adipocyte differentiation-related protein (ADRP)-containing lipid droplets have an essential role in the development of insulin resistance and atherosclerosis. Such droplets form in a cell-free system with a diameter of 0.1 to 0.4 µm, while the droplets present in cells vary in size, from small to very large, suggesting that the droplets can increase in size after being assembled. We have addressed this possibility.

Methods and Results— Experiments in NIH 3T3 cells demonstrated that the lipid droplets could increase in size independently of triglyceride biosynthesis. NIH 3T3 cells were either microinjected with ADRP–GFP (green fluorescent protein) or stained with Nile Red and followed by confocal microscopy and time-lapse recordings. The results showed that lipid droplets formed complexes with each other, with a volume equal to the sum of the merging particles. The formation of complexes could be inhibited by the nocodazole-induced depolymerization of the microtubules; thus, the process is dependent on microtubules. The presence of dynein on ADRP-containing droplets supports a role for this motor protein.

Conclusions— Lipid droplets can grow after they have been assembled. This increase in size is independent of triglyceride biosynthesis and involves formation of complexes, which requires intact microtubules.

Lipid droplets increase in size by a triglyceride biosynthesis–independent process after their assembly. Confocal microscopy and time-lapse recordings of 3T3 NIH cells, microinjected with ADRP–GFP or stained with Nile Red, indicated that complex formation between droplets could explain this increase in size. This process is dependent on intact microtubules.

Key Words: lipid droplets • lipid droplet fusion • adipocyte differentiation protein • microtubules

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