PPARα deficiency increases secretion and serum levels of apolipoprotein B-containing lipoproteins

Journal of Lipid Research

Mikael Alsterholm¹  Håkan Wennbo²  Daniel Lindén²  Jan Oscarsson³ 

[1]To whom correspondence should be addressed. e-mail:

[2]Department of Physiology, University of Göteborg, Box 434, S-405 30 Göteborg, Sweden

[3]Integrative Pharmacology, AstraZeneca R&D, S-431 83 Mölndal, Sweden

关键词: VLDL;    LDL;    apolipoprotein B-48;    apolipoprotein B-100;    triglycerides;    LDL receptor;   

DOI  :  

来源: DOAJ

【 摘 要 】

This study investigates the importance of peroxisome proliferator activated receptor α (PPARα) for serum apolipoprotein B (apoB) levels and hepatic secretion of apoB-containing lipoproteins. Total serum apoB and VLDL-apoB levels were higher in female PPARα-null mice compared with female wild-type mice, but no difference was seen in male mice. Furthermore, hepatic triglyceride secretion rate, determined in vivo after Triton WR1339 injection, was 2.4-fold higher in female PPARα-null mice compared with female wild-type mice, but no difference was observed in male mice. However, when fed a high fat diet, male PPARα-null mice displayed 2-fold higher serum levels of apoB and LDL cholesterol compared with male wild-type mice, but triglyceride levels were not affected. Hepatic LDL receptor protein levels were not influenced by PPARα deficiency, gender, or the fat diet. Hepatocyte cultures from female PPARα-null mice (cultured for 4 days in serum free medium) showed 2-fold higher total apoB secretion and increased secretion of apoB-48 VLDL, as well as 2.7-fold larger accumulation of VLDL-triglycerides in the medium compared with wild-type cultures. In conclusion, PPARα-deficient female mice, but not males, display high serum apoB associated with VLDL and increased hepatic triglyceride secretion. Moreover, male PPARα-null mice show increased susceptibility to high fat diet in terms of serum apoB levels.—Lindén, D., M. Alsterholm, H. Wennbo, and J. Oscarsson. PPARα deficiency increases secretion and serum levels of apolipoprotein B-containing lipoproteins.

【 授权许可】

Unknown