Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice

The regulation of liver apolipoprotein (apo) A-I gene expression by fibrates was studied in human apo A-I transgenic mice containing a human genomic DNA fragment driving apo A-I expression in liver. Treatment with fenofibrate (0.5% wt/wt) for 7 d increased plasma human apo A-I levels up to 750% and HDL-cholesterol levels up to 200% with a shift to larger particles. The increase in human apo A-I plasma levels was time and dose dependent and was already evident after 3 d at the highest dose (0.5% wt/wt) of fenofibrate. In contrast, plasma mouse apo A-I concentration was decreased after fenofibrate in nontransgenic mice. The increase in plasma human apo A-I levels after fenofibrate treatment was associated with a 97% increase in hepatic human apo A-I mRNA, whereas mouse apo A-I mRNA levels decreased to 51%. In nontransgenic mice, a similar down-regulation of hepatic apo A-I mRNA levels was observed. Nuclear run-on experiments demonstrated that the increase in human apo A-I and the decrease in mouse apo A-I gene expression after fenofibrate occurred at the transcriptional level. Since part of the effects of fibrates are mediated through the nuclear receptor PPAR (peroxisome proliferator-activated receptor), the expression of the acyl CoA oxidase (ACO) gene was measured as a control of PPAR activation. Both in transgenic and nontransgenic mice, fenofibrate induced ACO mRNA levels up to sixfold. When transgenic mice were treated with gemfibrozil (0.5% wt/wt) plasma human apo A-I and HDL-cholesterol levels increased 32 and 73%, respectively, above control levels. The weaker effect of this compound on human apo A-I and HDL-cholesterol levels correlated with a less pronounced impact on ACO mRNA levels (a threefold increase) suggesting that the level of induction of human apo A-I gene is related to the PPAR activating potency of the fibrate used. Treatment of human primary hepatocytes with fenofibric acid (500 microM) provoked an 83 and 50% increase in apo A-I secretion and mRNA levels, respectively, supporting that a direct action of fibrates on liver human apo A-I production leads to the observed increase in plasma apo A4 and HDL-cholesterol

Sovjan / Sovjan (Albanie)

Léra Pétrika, Prendi Frano, Touchais Gilles, Denèfle M., Dufaure J.-J., Fouache E., Hansen Julie M., Martinez S. Sovjan / Sovjan (Albanie). In: Iliria, vol. 26, 1996. pp. 225-272

Habiter le patrimoine

Comment les sociétés contemporaines « habitent-elles » les lieux, les sites, les monuments qu'elles constituent en patrimoine ? Comment investissent-elles le cadre matériel auquel elles attribuent une valeur patrimoniale et dans lequel elles sont, tout produire ? Autre question : que peuvent nous apprendre les modalités avec lesquelles les groupes sociaux réinvestissent les lieux patrimoniaux sur les rapports que ceux-ci entretiennent avec l'espace ? C'est à ces questions que cherchent à répondre les textes de trente-sept auteurs (des géographes, des sociologues, des historiens, des ethnologues) réunis dans cet ouvrage. Habiter le patrimoine explore ainsi la multitude des rapports que l'Homme tisse avec ses spatialités patrimoniales, les expressions de l'habiter, les pratiques qui s'y attachent, les contraintes qui y sont liées, les conflits générés ou le potentiel qui s'en dégage... dans le contexte de la société du début du XIXe siècle