Age-related decrease in expression of peroxisome proliferator-activated receptor α 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 α(PPARα) expression in livers of young and old rats were studied.Methods A total of 16...
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| Veröffentlicht in: | Chinese medical journal 2005-07, Vol.118 (13), p.1093-1098 |
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| description | 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 α(PPARα) 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 PPARα and its target genes.Western blotting was used to determine PPARα 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 PPARα mRNA (52%, P |
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To investigate potential molecular mechanisms, the effects of age and fibrate administration on peroxisome proliferator-activated receptor α(PPARα) 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 PPARα and its target genes.Western blotting was used to determine PPARα 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 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 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 PPARα expression in livers from either 24-month or 2-month-old rats.Conclusions The decrease in the hepatic PPARα 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.</description><identifier>ISSN: 0366-6999</identifier><identifier>EISSN: 2542-5641</identifier><identifier>PMID: 16098262</identifier><language>eng</language><publisher>China: Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China</publisher><subject>Aging - metabolism ; Animals ; Fenofibrate - pharmacology ; Fenofibrate - therapeutic use ; Hyperlipidemias - drug therapy ; Hyperlipidemias - etiology ; Lipids - blood ; Liver - metabolism ; Male ; PPAR alpha - genetics ; Rats ; Rats, Sprague-Dawley ; 脂质代谢 ; 药物治疗 ; 过氧物酶体 ; 酶活性</subject><ispartof>Chinese medical journal, 2005-07, Vol.118 (13), p.1093-1098</ispartof><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/85656X/85656X.jpg</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16098262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Ping</creatorcontrib><creatorcontrib>Wang, Zhao-jun</creatorcontrib><creatorcontrib>Zhang, Xiu-jin</creatorcontrib><creatorcontrib>Zhao, Ya-li</creatorcontrib><title>Age-related decrease in expression of peroxisome proliferator-activated receptor α and its effects on development of dyslipidemia</title><title>Chinese medical journal</title><addtitle>Chinese Medical Journal</addtitle><description>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 α(PPARα) 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 PPARα and its target genes.Western blotting was used to determine PPARα 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 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 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 PPARα expression in livers from either 24-month or 2-month-old rats.Conclusions The decrease in the hepatic PPARα 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.</description><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Fenofibrate - pharmacology</subject><subject>Fenofibrate - therapeutic use</subject><subject>Hyperlipidemias - drug therapy</subject><subject>Hyperlipidemias - etiology</subject><subject>Lipids - blood</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>PPAR alpha - genetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>脂质代谢</subject><subject>药物治疗</subject><subject>过氧物酶体</subject><subject>酶活性</subject><issn>0366-6999</issn><issn>2542-5641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtKxDAUhosoznh5BQku3BXSNJdmKeINBtzouqTJyUzGNqlJx9vSN_JFfCbjDVc_HL7z_ZyzVcwJo6RknFbbxRzXnJdcSjkr9lJaY0wYE3y3mFUcy4ZwMi_eTpdQRujVBAYZ0BFUAuQ8gucxQkoueBQsGiGGZ5fCAGiMoXcWoppCLJWe3OP3bgQNYx6hj3ekvEFuSgisBZ0zOww8Qh_GAfz05TMvqXejMzA4dVDsWNUnOPzN_eLu4vz27Kpc3Fxen50uSl01RJRUKmqkkVxxIaETWNe1UNZ0mhLBuloYqGvOsCECM42Z1bzJ_QxLS6noWL1fnPx4n5S3yi_bddhEnxvb15Ue1gRjVtUYi38wn_qwgTS1g0sa-l55CJvU8oYK3lQ0g0e_4KYbwLRjdIOKL-3fezNw_APoVfDLB5dLO6XvreshQ6QiNFs-AQwNhbE</recordid><startdate>20050705</startdate><enddate>20050705</enddate><creator>Ye, Ping</creator><creator>Wang, Zhao-jun</creator><creator>Zhang, Xiu-jin</creator><creator>Zhao, Ya-li</creator><general>Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>20050705</creationdate><title>Age-related decrease in expression of peroxisome proliferator-activated receptor α and its effects on development of dyslipidemia</title><author>Ye, Ping ; Wang, Zhao-jun ; Zhang, Xiu-jin ; Zhao, Ya-li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1827-49a4d9d96a679eb70c337afdbc4275b37de33650d2705c05fc68ffe509f447b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Aging - metabolism</topic><topic>Animals</topic><topic>Fenofibrate - pharmacology</topic><topic>Fenofibrate - therapeutic use</topic><topic>Hyperlipidemias - drug therapy</topic><topic>Hyperlipidemias - etiology</topic><topic>Lipids - blood</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>PPAR alpha - genetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>脂质代谢</topic><topic>药物治疗</topic><topic>过氧物酶体</topic><topic>酶活性</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ye, Ping</creatorcontrib><creatorcontrib>Wang, Zhao-jun</creatorcontrib><creatorcontrib>Zhang, Xiu-jin</creatorcontrib><creatorcontrib>Zhao, Ya-li</creatorcontrib><collection>维普_期刊</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>维普中文期刊数据库</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>Chinese medical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ye, Ping</au><au>Wang, Zhao-jun</au><au>Zhang, Xiu-jin</au><au>Zhao, Ya-li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age-related decrease in expression of peroxisome proliferator-activated receptor α and its effects on development of dyslipidemia</atitle><jtitle>Chinese medical journal</jtitle><addtitle>Chinese Medical Journal</addtitle><date>2005-07-05</date><risdate>2005</risdate><volume>118</volume><issue>13</issue><spage>1093</spage><epage>1098</epage><pages>1093-1098</pages><issn>0366-6999</issn><eissn>2542-5641</eissn><abstract>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 α(PPARα) 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 PPARα and its target genes.Western blotting was used to determine PPARα 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 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 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 PPARα expression in livers from either 24-month or 2-month-old rats.Conclusions The decrease in the hepatic PPARα 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.</abstract><cop>China</cop><pub>Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China</pub><pmid>16098262</pmid><tpages>6</tpages></addata></record> |
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| subjects | Aging - metabolism Animals Fenofibrate - pharmacology Fenofibrate - therapeutic use Hyperlipidemias - drug therapy Hyperlipidemias - etiology Lipids - blood Liver - metabolism Male PPAR alpha - genetics Rats Rats, Sprague-Dawley 脂质代谢 药物治疗 过氧物酶体 酶活性 |
| title | Age-related decrease in expression of peroxisome proliferator-activated receptor α and its effects on development of dyslipidemia |
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