title: SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity.
abstract: The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes. Such droplets are formed as small structures that increase in size through fusion, a process that is dependent on intact microtubules and the motor protein dynein. Approximately 15% of all droplets are involved in fusion processes at a given time. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), alpha-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 alpha-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.
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska Univeristy Hospital, SE-413 45 Göteborg, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Boström
authors.forename: Linda
authors.initials: L
authors.lastname: Andersson
authors.forename: Mikael
authors.initials: M
authors.lastname: Rutberg
authors.forename: Jeanna
authors.initials: J
authors.lastname: Perman
authors.forename: Ulf
authors.initials: U
authors.lastname: Lidberg
authors.forename: Bengt R
authors.initials: BR
authors.lastname: Johansson
authors.forename: Julia
authors.initials: J
authors.lastname: Fernandez-Rodriguez
authors.forename: Johanna
authors.initials: J
authors.lastname: Ericson
authors.forename: Tommy
authors.initials: T
authors.lastname: Nilsson
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Sven-Olof
authors.initials: SO
authors.lastname: Olofsson
mesh_terms: D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism*; D007333:Insulin Resistance; D008055:Lipids / Q000502:physiology*; D008561:Membrane Fusion; D051379:Mice; D041681:NIH 3T3 Cells; D019301:Oleic Acid / Q000494:pharmacology*; D050600:SNARE Proteins / Q000502:physiology*
chemical_list: D008055:Lipids; D050600:SNARE Proteins; D019301:Oleic Acid