Journal
JOURNAL OF LIPID RESEARCH
Volume 47, Issue 2, Pages 329-340Publisher
ELSEVIER
DOI: 10.1194/jlr.M500203-JLR200
Keywords
Wy14,643; primary hepatocytes; triglyceride synthesis; fatty acid oxidation; triglyceride secretion; apolipoprotein B-100; apolipoprotein B-48; peroxisome proliferator-activated receptor alpha
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Adipose differentiation-related protein ( ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor a ( PPAR alpha) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride content increased. Also in primary mouse hepatocytes, Wy increased ADRP expression and intracellular triglyceride mass. The triglyceride mass increased in spite of unchanged triglyceride biosynthesis and increased palmitic acid oxidation. However, Wy incubation decreased the secretion of newly synthesized triglycerides, whereas apolipoprotein B secretion increased. Thus, decreased availability of triglycerides for VLDL assembly could help to explain the cellular accumulation of triglycerides after Wy treatment. We hypothesized that this effect could be mediated by increased ADRP expression. Similar to PPARa activation, adenovirus-mediated ADRP overexpression in mouse hepatocytes enhanced cellular triglyceride mass and decreased the secretion of newly synthesized triglycerides. In ADRP-overexpressing cells, Wy incubation resulted in a further decrease in triglyceride secretion. This effect of Wy was not attributable to decreased cellular triglycerides after increased fatty acid oxidation because the triglyceride mass in Wy-treated ADRP-overexpressing cells was unchanged. In summary, PPARa activation prevents the availability of triglycerides for VLDL assembly and increases hepatic triglyceride content in part by increasing the expression of ADRP.-Edvardsson, U., A. Ljungberg, D. Linden, L. William-Olsson, H. Peilot-Sjogren, A. Ahnmark, and J. Oscarsson. PPARa activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes.
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