Lack of hypotriglyceridemic effect of gemfibrozil as a consequence of age-related changes in rat liver PPARalpha.

Détails

ID Serval
serval:BIB_AAA10B68BD71
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lack of hypotriglyceridemic effect of gemfibrozil as a consequence of age-related changes in rat liver PPARalpha.
Périodique
Biochemical Pharmacology
Auteur⸱e⸱s
Sanguino E., Ramón M., Michalik L., Wahli W., Alegret M., Sánchez R.M., Vázquez-Carrera M., Laguna J.C.
ISSN
0006-2952[print], 0006-2952[linking]
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
67
Numéro
1
Pages
157-166
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
We have investigated if changes in hepatic lipid metabolism produced by old age are related to changes in liver peroxisome proliferator-activated receptor alpha (PPARalpha). Our results indicate that 18-month-old rats showed a marked decrease in the expression and activity of liver PPARalpha, as shown by significant reductions in PPARalpha mRNA, protein and binding activity, resulting in a reduction in the relative mRNA levels of PPARalpha target genes, such as liver-carnitine-palmitoyl transferase-I (CPT-I) and mitochondrial medium-chain acyl-CoA dehydrogenase (MCAD). Further, in accordance with a liver PPARalpha deficiency in old rats, treatment of old animals with a therapeutic dose of gemfibrozil (GFB) (3mg/kg per day, 21 days) was ineffective in reducing plasma triglyceride concentrations (TG), despite attaining a 50% reduction in TG when GFB was administered to young animals at the same dose and length of treatment. We hypothesize that the decrease in hepatic PPARalpha can be related to a state of leptin resistance present in old animals.
Mots-clé
Acyl-CoA Oxidase/metabolism, Aging/physiology, Animals, Antilipemic Agents/pharmacology, CCAAT-Enhancer-Binding Proteins/metabolism, DNA-Binding Proteins/metabolism, Gemfibrozil/pharmacology, Gene Expression, Leptin/metabolism, Liver/drug effects, Liver/metabolism, Male, NF-kappa B/metabolism, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear/metabolism, Sterol Regulatory Element Binding Protein 1, Transcription Factors/metabolism, Triglycerides/blood, Triglycerides/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 15:44
Dernière modification de la notice
20/08/2019 15:14
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