Letter abstract
Nature Cell Biology 9, 1286 - 1293 (2007)
Published online: 7 October 2007 | doi:10.1038/ncb1648
SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity
Pontus Boström1, Linda Andersson1, Mikael Rutberg1, Jeanna Perman1, Ulf Lidberg1, Bengt R. Johansson2, Julia Fernandez-Rodriguez2, Johanna Ericson1, Tommy Nilsson2, Jan Borén1 & Sven-Olof Olofsson1
The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes1. Such droplets are formed as small structures2 that increase in size through fusion3, a process that is dependent on intact microtubules and the motor protein dynein3, 4. Approximately 15% of all droplets are involved in fusion processes at a given time3. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), 
-SNAP (soluble NSF attachment protein) and the SNAREs (SNAP receptors), SNAP23 (synaptosomal-associated protein of 23 kDa), syntaxin-5 and VAMP4 (vesicle-associated membrane protein 4). Knockdown of the genes for SNAP23, syntaxin-5 or VAMP4, or microinjection of a dominant-negative mutant of -SNAP, decreases the rate of fusion and the size of the lipid droplets. Thus, the SNARE system seems to have an important role in lipid droplet fusion. We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23. Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell.
- Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska Univeristy Hospital, SE-413 45 Göteborg, Sweden.
- Department of Biomedicine, University of Göteborg, Göteborg, Sweden.
Correspondence to: Sven-Olof Olofsson1 e-mail: Sven-Olof.Olofsson@wlab.gu.se
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