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

Artikel i vetenskaplig tidskrift
Författare D Lindén
Mikael Alsterholm
H Wennbo
J Oscarsson
Publicerad i Journal of lipid research
Volym 42
Nummer/häfte 11
Sidor 1831-40
ISSN 0022-2275
Publiceringsår 2001
Publicerad vid Institutionen för fysiologi och farmakologi, Avdelningen för fysiologi
Sidor 1831-40
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Animals, Apolipoproteins B, blood, genetics, secretion, Blotting, Western, Cells, Cultured, Cholesterol, blood, Cholesterol, LDL, blood, Dietary Fats, administration & dosage, Lipoproteins, blood, secretion, Lipoproteins, VLDL, blood, metabolism, Liver, secretion, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger, analysis, Receptors, Cytoplasmic and Nuclear, deficiency, genetics, Receptors, LDL, analysis, Transcription Factors, deficiency, genetics, Triglycerides, blood
Ämneskategorier Fysiologi

Sammanfattning

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.

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