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Biotech / Medical : The thread of life -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (298)	3/23/2002 8:08:15 PM
From: sim1	Read Replies (1) \| Respond to of 1336

Abstract from Folia Pharmacologica Japonica (Nov 2001) This abstract appeared to be relevant to your topic and I thought it might be of interest. Advanced apologies if not. Folia Pharmacol. Jpn. (Nippon Yakurigaku Zasshi) 118 (5), 321-326 (2001) PPARƒÁ agonist and antagonist Takashi KADOWAKI Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo ‚P‚P‚R]‚W‚U‚T‚T, Japan Abstract: Peroxisome proliferator]activated receptor ƒÁ iPPARƒÁj is a ligand]activated transcription factor and functions as a heterodimer with a retinoid X receptor iRXRj. Supraphysiological activation of PPARƒÁ by thiazolidinediones can reduce insulin resistance and hyperglycemia in type ‚Q diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARƒÁ activity observed in heterozygous PPARƒÁ]deficient mice or the Pro ‚P‚Q Ala polymorphism in human PPARƒÁ has been shown to prevent insulin resistance and obesity induced by a high]fat iHFj diet. We investigated whether functional antagonism toward PPARƒÁ^RXR could be used to treat obesity and type ‚Q diabetes. We show herein that moderate reduction of PPARƒÁ with an RXR antagonist or a PPARƒÁ antagonist decreases triglyceride iTGj content in white adipose tissue, skeletal muscle and liver. These inhibitors potentiate leptin's effects and stimulated adiponectin levels, which increases fatty acid combustion and energy dissipation, thereby ameliorating HF diet]induced obesity and insulin resistance. Paradoxically, severe reduction of PPARƒÁ by treatment of heterozygous PPARƒÁ]deficient mice with an RXR antagonist or a PPARƒÁ antagonist depletes white adipose tissue and markedly decreases leptin and adiponectin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re]emergence of insulin resistance. Our data suggest that appropriate functional antagonism of PPARƒÁ^RXR may be a logical approach to protection against obesity and related diseases such as type ‚Q diabetes. Keywords: PPARƒÁ; antagonist; adipocyte hypertrophy; insulin resistance wwwsoc.nii.ac.jp