PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes

Journal of Lipid Research

Daniel Lindén¹  Andrea Ahnmark¹  Helena Peilot-Sjögren²  Anna Ljungberg²  Ulrika Edvardsson³  Lena William-Olsson³  Jan Oscarsson³ 

[1] AstraZeneca Research and Development, Mölndal, Sweden;Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden;Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden;

关键词: Wy14,643;    primary hepatocytes;    triglyceride synthesis;    fatty acid oxidation;    triglyceride secretion;    apolipoprotein B-100;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 α (PPARα) 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 PPARα 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, PPARα activation prevents the availability of triglycerides for VLDL assembly and increases hepatic triglyceride content in part by increasing the expression of ADRP.

【 授权许可】

Unknown