on March 12, 2009
Published online before print March 12, 2009, doi: 10.1161/ATVBAHA.108.182675
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Submitted on July 31, 2008
Accepted on February 18, 2009
TIP47, a Lipid Cargo Protein Involved in Macrophage Triglyceride Metabolism
Insa Buers *;
From the Leibniz Institute for Arteriosclerosis Research (I.B., H.R., O.H.), Muenster, Germany; the Institute of Nutrition (S.L.), University of Jena, Germany; the Department of General Pediatrics (Y.N.), University Children's Hospital, Münster, Germany; and the National Heart and Lung Institute (N.J.S.), Imperial College London, UK.
* To whom correspondence should be addressed. E-mail: i_buer01{at}uni-muenster.de.
Objective—Uptake of lipids by macrophages (M
) leads to lipid droplet accumulation and foam cell formation. The PAT family proteins are implicated in lipid droplet formation, but the precise function of the 47-kDa tail interacting protein (TIP47), a member of this family, is poorly defined. The present study was performed to determine the function of TIP47 in M lipid metabolism.
Methods and Results—Freeze-fracture cytochemistry demonstrates that TIP47 is present in the plasma membrane of M and is aggregated into clusters when the cells are incubated with oleate. Suppression of adipophilin levels using siRNA knockdown leads to migration of TIP47 from a cytoplasmic pool to the lipid droplet. Further, reduction of TIP47 decreases triglyceride levels, whereas raising TIP47 levels by expression of EGFP-TIP47 shows the opposite effect.
Conclusion—Our results show that the TIP47 protein levels directly correlate with triglyceride levels. We propose that TIP47 may act as a carrier protein for free fatty acids and in this way participates in conversion of M into foam cells.
Key words: TIP47 • triglyceride metabolism • macrophages • PAT proteins • lipid droplets