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

This study investigates the importance of peroxisome proliferator activated receptor alpha (PPAR alpha) for serum apolipoprotein B (apoB) levels and h epatic secretion of apoB-containing lipoproteins. Total serum apoB and VLDL , apoB levels were higher in female PPAR alpha -null mice compared with fem ale wild-type mice, but no difference was seen in male mice. Furthermore, h epatic triglyceride secretion rate, determined in vivo after Triton WR1339 injection, was 2.4-fold higher in female PPAR alpha -null mice compared wit h female wild-type mice, but no difference was observed in male mice. Howev er, when fed a high fat diet, male PPAR alpha -null mice displayed 2-fold h igher serum levels of apoB and LDL cholesterol compared with male wild-type mice, but triglyceride levels were not affected. Hepatic LDL receptor prot ein levels were not influenced by PPAR alpha deficiency, gender, or the fat diet. Hepatocyte cultures from female PPAR alpha -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 accumulatio n of VLDL-triglycerides in the medium compared with wild-type cultures. In conclusion, PPAR alpha -deficient female mice, but not males, display high serum apoB associated with VLDL and increased hepatic triglyceride secretio n. Moreover, male PPAR alpha -null mice show increased susceptibility to hi gh fat diet in terms of serum apoB levels.