Age-related decrease in expression of peroxisome proliferator-activated receptor alpha and its effects on development of dyslipidemia.
BACKGROUND
Ageing is associated with increased incidence of dyslipidemia. To investigate potential molecular mechanisms, the effects of age and fibrate administration on peroxisome proliferator-activated receptor alpha (PPARalpha) expression in livers of young and old rats were studied.


METHODS
A total of 16 young (2-month-old) and 16 old rats (24-month-old) were randomly assigned to a control group and fenofibrate group (fenofibrate in a total therapeutic dosage of 0.5% in ratio to each treated rat weight in 14 days). RT-PCR was applied to evaluate hepatic mRNA expression of PPARalpha and its target genes. Western blotting was used to determine PPARalpha protein level in liver tissue.


RESULTS
When compared with 2-month-old rats, the liver tissue from 24-month-old rats showed reduced expression of PPARalpha mRNA (52%, P < 0.05) and protein (109%, P < 0.01). Consequently, the mRNA levels of PPAR target genes, LPL, ACO, ACS and CPT-1 were markedly lowered by 19%, 8%, 13% and 9% respectively, and apoCIII increased by 24% in livers from 24-month-old rats, compared with values obtained from 2-month-old rats (P < 0.05). Fenofibrate therapy significantly lowered plasma triglyceride and total cholesterol levels in old rats, accompanied with improvement in hepatic expression of genes, including LPL, ACO, ACS, CPT-1 and apoCIII, but no change was found in PPARalpha expression in livers from either 24-month or 2-month-old rats.


CONCLUSIONS
The decrease in the hepatic PPARalpha expression is probably directly related to the lipid metabolic disturbances observed in old animals. The beneficial effects of fenofibrate administration in old rats suggests that fibrates may be useful for treating lipid disturbances in old people.
Ye
Ping
P
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China. yeping@sina.com
Wang
Zhao-jun
ZJ
Zhang
Xiu-jin
XJ
Zhao
Ya-li
YL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy / Q000209:etiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008055:Lipids; D047493:PPAR alpha; D011345:Fenofibrate