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Journal of Lipid Research, Vol. 42, 1831-1840, November 2001
Copyright © 2001 by Lipid Research, Inc.

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

Correspondence to: Daniel Lindén, To whom correspondence should be addressed., daniel.linden{at}fysiologi.gu.se (E-mail)

This study investigates the importance of peroxisome proliferator activated receptor (PPAR) for serum apolipoprotein B (apoB) levels and hepatic secretion of apoB-containing lipoproteins. Total serum apoB and VLDL-apoB levels were higher in female PPAR-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 PPAR-null mice compared with female wild-type mice, but no difference was observed in male mice. However, when fed a high fat diet, male PPAR-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 PPAR deficiency, gender, or the fat diet. Hepatocyte cultures from female PPAR-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, PPAR-deficient female mice, but not males, display high serum apoB associated with VLDL and increased hepatic triglyceride secretion. Moreover, male PPAR-null mice show increased susceptibility to high fat diet in terms of serum apoB levels. — Lindén, D., M. Alsterholm, H. Wennbo, and J. Oscarsson. PPAR deficiency increases secretion and serum levels of apolipoprotein B-containing lipoproteins. J. Lipid Res. 2001. 42: 1831–1840.

Supplementary key words: VLDL, LDL, apolipoprotein B-48, apolipoprotein B-100, triglycerides, LDL receptor, hepatocytes, dietary fat, gender, cholesterol

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