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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1566.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Adipocyte Differentiation-Related Protein Promotes Fatty Acid Storage in Cytosolic Triglycerides and Inhibits Secretion of Very Low–Density Lipoproteins

Björn Magnusson; Lennart Asp; Pontus Boström; Michel Ruiz; Pia Stillemark-Billton; Daniel Lindén; Jan Borén; Sven-Olof Olofsson

From the Wallenberg Laboratory for Cardiovascular Research (B.M., L.A., P.B., M.R., P.S.-B., J.B., S.-O.O.), Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden; and AstraZeneca (D.L.), Mölndal, Sweden.

Correspondence to Sven-Olof Olofsson, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. E-mail Sven-Olof.Olofsson{at}wlab.gu.se

Objective— We investigated the role of adipocyte differentiation-related protein (ADRP) in triglyceride turnover and in the secretion of very low–density lipoprotein (VLDL) from McA-RH7777 cells and primary rat hepatocytes.

Methods and Results— An increase in the expression of ADRP increased triglyceride accumulation in cytosolic lipid droplets and prevented the incorporation of fatty acids into secretable triglycerides, thereby reducing the secretion of triglycerides as well as of apolipoprotein B-100 (apoB-100) and apoB-48 VLDL. The ability of ADRP to block the secretion of apoB-100 VLDL1 decreased with increasing quantities of fatty acids in the medium, indicating a saturable process and emphasizing the importance of sequestering of fatty acids for the effect of ADRP on VLDL secretion. Knockdown (small interfering RNA) of ADRP decreased the pool of cytosolic lipid droplets but increased only the secretion of apoB-48 VLDL1. Additionally, there was an increased flow of fatty acids into ß-oxidation.

Conclusions— ADRP is essential for the accumulation of triglycerides in cytosolic lipid droplets. An increase in ADRP prevents the formation of VLDL by diverting fatty acids from the VLDL assembly pathway into cytosolic triglycerides, whereas a decrease of the protein increases the sorting of fatty acids to ß-oxidation and promotes the secretion of apoB-48 VLDL1.

An increase in the amount of ADRP sequestered fatty acids in triglycerides in cytosolic lipid droplets and prevented them from being incorporated into triglycerides of VLDL. A knockdown (siRNA) decreased the pool of cytosolic lipid droplets and promoted the ß-oxidation of the stored fatty acids and the secretion of apoB-48 VLDL1.

Key Words: adipose differentiation–related protein • cytosolic lipid droplets • apolipoproteins B • ß-oxidation • small interfering RNA

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