Inhibition of the actions of peroxisome proliferator-activated receptor alpha on obesity by estrogen.
OBJECTIVE
To determine whether the major ovarian factor estrogen modulates peroxisome proliferator-activated receptor (PPAR) alpha actions on obesity and to investigate the mechanism by which estrogen regulates PPARalpha actions.


METHODS
Female ovariectomized mice were randomly divided into four groups (n = 8/group). After they were treated with combinations of high fat, fenofibrate (FF), or 17beta-estradiol (E) for 13 weeks, variables and determinants of obesity and lipid metabolism were measured using in vivo and in vitro approaches.


RESULTS
When female ovariectomized mice were given a high-fat diet with either FF or E, body weight gain and white adipose tissue mass were significantly reduced and serum lipid profiles were improved compared with control mice fed a high-fat diet alone. When mice were concomitantly treated with FF and E, however, E reversed the effects of FF on body weight gain, serum lipid profiles, and hepatic PPARalpha target gene expression. Consistent with the in vivo data, E not only decreased basal levels of PPARalpha reporter gene activation but also significantly decreased Wy14,643-induced luciferase reporter activity. In addition, inhibition of PPARalpha functions by E did not seem to occur by interfering with the DNA binding of PPARalpha.


CONCLUSIONS
Our results demonstrate that in vivo and in vitro treatment of estrogen inhibited the actions of FF-activated PPARalpha on obesity and lipid metabolism through changes in the expression of PPARalpha target genes, providing evidence that FF does not regulate obesity in female mice with functioning ovaries.
Jeong
Sunhyo
S
Department of Life Sciences, Mokwon University, Taejon 302-729, Korea.
Yoon
Michung
M
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D047493:PPAR alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D008055:Lipids; D047493:PPAR alpha; D004958:Estradiol; D011345:Fenofibrate