High density lipoprotein turnover is dependent on peroxisome proliferator-activated receptor α in mice.
OBJECTIVE
Peroxisome proliferator-activated receptor (PPAR) α is a nuclear receptor that through sensing fatty acid metabolites as ligands regulates genes involved in lipid transport and metabolism (Atherosclerosis 205: 413, 2009). Disruption of the PPARα gene, however, may not lead to apparent changes in phenotypes, perhaps due to compensation by other members of the nuclear receptor superfamily. We characterized cholesterol homeostasis in PPARα-null mice on a C57BL/6 background with a focus on HDL metabolism.


RESULTS
PPARα-null mice gained weight significantly more than wild-type mice, with more prominence in females, without changing the HDL-apoprotein clearance rate. Clearance of plasma HDL-cholesteryl ester was retarded, more prominently in females. Uptake of HDL-cholesteryl ester by the adrenal glands and ovaries was found to be decreased in female mutant mice. The ATP binding cassette transporter A1 (ABCA1), liver X receptor α and PPARδ mRNAs were decreased in the liver, and that encoding scavenger receptor B1 (SR-B1) decreased in the adrenal glands of these mice. Although the plasma lipoprotein profile did not show major differences, some subtle changes were found in the mutants, including HDL properties being consistent with its slow turnover. Cholesterol content in the organs was not significantly influenced except for a paradoxical increase in gonad glands.


CONCLUSIONS
We conclude that the plasma HDL turnover rate is retarded in PPARα-null mice, perhaps more prominently in females.
Akita
Nobukatsu
N
Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Tsujita
Maki
M
Yokota
Tomo
T
Gonzalez
Frank J
FJ
Ohte
Nobuyuki
N
Kimura
Genjiro
G
Yokoyama
Shinji
S
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002788:Cholesterol Esters / Q000378:metabolism*; D005260:Female; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002788:Cholesterol Esters; C059714:HDL cholesteryl ester; D008075:Lipoproteins, HDL; D047493:PPAR alpha; D012333:RNA, Messenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B