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Publication : Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight.

First Author  Chaput E Year  2000
Journal  Biochem Biophys Res Commun Volume  271
Issue  2 Pages  445-50
PubMed ID  10799317 Mgi Jnum  J:62209
Mgi Id  MGI:1858575 Doi  10.1006/bbrc.2000.2647
Citation  Chaput E, et al. (2000) Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun 271(2):445-50
abstractText  Activators of peroxisome proliferator activated receptors (PPARs) are effective drugs to improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin-resistance, and atherosclerosis. We compared the pharmacological profile of a PPARalpha activator, fenofibrate, and a PPARgamma activator, rosiglitazone, on serum parameters, target gene expression, and body weight gain in (fa/fa) fatty Zucker rats and db/db mice as well as their association in db/db mice. Fenofibrate faithfully modified the expression of PPARalpha responsive genes. Rosiglitazone increased adipose tissue aP2 mRNA in both models while increasing liver acyl CoA oxidase mRNA in db/db mice but not in fatty Zucker rats. Both drugs lowered serum triglycerides yet rosiglitazone markedly increased body weight gain while fenofibrate decreased body weight gain in fatty Zucker rats. KRP 297, which has been reported to be a PPARalpha and gamma co-activator, also affected serum triglycerides and insulin in fatty Zucker rats although no change in body weight gain was noted. These results serve to clearly differentiate the metabolic finality of two distinct classes of drugs, as well as their corresponding nuclear receptors, having similar effects on serum triglycerides. Copyright 2000 Academic Press.
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