PPARalpha deficiency increases secretion and serum levels of apolipoprotein B-containing lipoproteins.
This study investigates the importance of peroxisome proliferator activated receptor alpha (PPARalpha) for serum apolipoprotein B (apoB) levels and hepatic secretion of apoB-containing lipoproteins. Total serum apoB and VLDL-apoB levels were higher in female PPARalpha-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 PPARalpha-null mice compared with female wild-type mice, but no difference was observed in male mice. However, when fed a high fat diet, male PPARalpha-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 PPARalpha deficiency, gender, or the fat diet. Hepatocyte cultures from female PPARalpha-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, PPARalpha-deficient female mice, but not males, display high serum apoB associated with VLDL and increased hepatic triglyceride secretion. Moreover, male PPARalpha-null mice show increased susceptibility to high fat diet in terms of serum apoB levels.
Lindén
D
D
Department of Physiology, University of Göteborg, Box 434, S-405 30 Göteborg, Sweden. daniel.linden@fysiologi.gu.se
Alsterholm
M
M
Wennbo
H
H
Oscarsson
J
J
D000818:Animals; D001055:Apolipoproteins B / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics; D011973:Receptors, LDL / Q000032:analysis; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D004041:Dietary Fats; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol