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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:767.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

TIP47, a Lipid Cargo Protein Involved in Macrophage Triglyceride Metabolism

Insa Buers; Horst Robenek; Stefan Lorkowski; Yvonne Nitschke; Nicholas J. Severs; Oliver Hofnagel

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.

Correspondence to Insa Buers, Leibniz Institute for Arteriosclerosis Research, Domagkstr. 3, 48149 Muenster, Germany. 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.

The function of TIP47 on M lipid metabolism was investigated. TIP47 protein levels were found to directly correlate with triglyceride levels. From this and other experimental evidence, we propose that TIP47 acts as a carrier protein for free fatty acids and thereby participates in conversion of M into foam cells.

Key Words: TIP47 • triglyceride metabolism • macrophages • PAT proteins • lipid droplets