Adipocyte differentiation-related protein promotes fatty acid storage in cytosolic triglycerides and inhibits secretion of very low-density lipoproteins.
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.


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 beta-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 beta-oxidation and promotes the secretion of apoB-48 VLDL1.
Magnusson
Björn
B
Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Asp
Lennart
L
Boström
Pontus
P
Ruiz
Michel
M
Stillemark-Billton
Pia
P
Lindén
Daniel
D
Borén
Jan
J
Olofsson
Sven-Olof
SO
D000818:Animals; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D000070780:Perilipin-2; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D014280:Triglycerides / Q000378:metabolism*
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D008565:Membrane Proteins; D000070780:Perilipin-2; C000602984:Plin2 protein, rat; D034741:RNA, Small Interfering; D014280:Triglycerides