SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity.
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.
Boström
Pontus
P
Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska Univeristy Hospital, SE-413 45 Göteborg, Sweden.
Andersson
Linda
L
Rutberg
Mikael
M
Perman
Jeanna
J
Lidberg
Ulf
U
Johansson
Bengt R
BR
Fernandez-Rodriguez
Julia
J
Ericson
Johanna
J
Nilsson
Tommy
T
Borén
Jan
J
Olofsson
Sven-Olof
SO
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*
D008055:Lipids; D050600:SNARE Proteins; D019301:Oleic Acid