Age-related decrease in expression of peroxisome proliferator-activated receptor α and its effects on development of dyslipidemia  

作　　者：YEPing WANGZhao-jun ZHANGXiu-jin ZHAOYa-li 

机构地区：[1]DepartmentofGeriatricCardiology,ChinesePLAGeneralHospital,Beijing100853,China

出　　处：《Chinese Medical Journal》2005年第13期1093-1098,共6页中华医学杂志（英文版）

基　　金：ThisstudywassupportedbyagrantfromNational"973"Foundation(No G2000057007)

摘　　要：Background Ageing is associated with increased incidence of dyslipidemia. Toinvestigate potential molecular mechanisms, the effects of age and fibrate administration onperoxisome proliferator-activated receptor α (PPARα) expression in livers of young and old ratswere studied. Methods A total of 16 young (2-month-old) and 16 old rats (24-month-old) were randomlyassigned 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 mRNAexpression of PPARα and its target genes. Western blotting was used to determine PPARα proteinlevel in liver tissue. Results When compared with 2-month-old rats, the liver tissue from24-month-old rats showed reduced expression of PPARα 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 markedlylowered by 19% , 8% , 13% and 9% respectively, and apoCⅢ increased by 24% in livers from24-month-old rats, compared with values obtained from 2-month-old rats ( P < 0. 05 ) . Fenofibratetherapy 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 andapoCⅢ, but no change was found in PPARα expression in livers from either 24-month or 2-month-oldrats. Conclusions The decrease in the hepatic PPARα expression is probably directly related to thelipid metabolic disturbances observed in old animals. The beneficial effects of fenofibrateadministration in old rats suggests that fibrates may be useful for treating lipid disturbances inold people.Background Ageing is associated with increased incidence of dyslipidemia. Toinvestigate potential molecular mechanisms, the effects of age and fibrate administration onperoxisome proliferator-activated receptor α (PPARα) expression in livers of young and old ratswere studied. Methods A total of 16 young (2-month-old) and 16 old rats (24-month-old) were randomlyassigned 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 mRNAexpression of PPARα and its target genes. Western blotting was used to determine PPARα proteinlevel in liver tissue. Results When compared with 2-month-old rats, the liver tissue from24-month-old rats showed reduced expression of PPARα 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 markedlylowered by 19% , 8% , 13% and 9% respectively, and apoCⅢ increased by 24% in livers from24-month-old rats, compared with values obtained from 2-month-old rats ( P < 0. 05 ) . Fenofibratetherapy 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 andapoCⅢ, but no change was found in PPARα expression in livers from either 24-month or 2-month-oldrats. Conclusions The decrease in the hepatic PPARα expression is probably directly related to thelipid metabolic disturbances observed in old animals. The beneficial effects of fenofibrateadministration in old rats suggests that fibrates may be useful for treating lipid disturbances inold people.

关 键 词：ageing peroxisome proliferator-activated receptor α FENOFIBRATE LIPID 

分 类 号：R589.2[医药卫生—内分泌]