the effect of ppar, ppar, ppar, and pparpan agonists on body weight, body mass, and serum lipid profiles in diet-induced obese akrj miceppar的影响,ppar,ppar pparpan受体激动剂在体重、体重、血清脂质在食源性肥胖akrj老鼠.pdfVIP

Hindawi Publishing Corporation PPAR Research Volume 2007, Article ID 97125, 13 pages doi:10.1155/2007/97125 Research Article The Effect of PPARα, PPARδ, PPARγ, and PPARpan Agonists on Body Weight, Body Mass, and Serum Lipid Profiles in Diet-Induced Obese AKR/J Mice W. Wallace Harrington, Christy S. Britt, Joan G. Wilson, Naphtali O. Milliken, Jane G. Binz, David C. Lobe, William R. Oliver, Michael C. Lewis, and Diane M. Ignar Department of Metabolic Diseases, GlaxoSmithKline Research, Research Triangle Park, NC 27709, USA Received 18 November 2006; Revised 8 February 2007; Accepted 3 March 2007 Recommended by Francine M. Gregoire Activation of peroxisome proliferator-activated receptor (PPAR) α, δ, and γ subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. PPARpan agonists which activate all three receptor subtypes have antidiabetic activity in animal models without the weight gain associated with selective PPARγ agonists. Herein we report the effects of selective PPAR agonists (GW9578, a PPARα agonist, GW0742, a PPARδ agonist, GW7845, a PPARγ agonist), combination of PPARα and δ agonists, and PPARpan (PPARα/γ/δ) activators (GW4148 or GW9135) on body weight (BW), body composition, food consumption, fatty acid oxidation, and serum chemistry of diet-induced obese AKR/J mice. PPARα or PPARδ agonist treatment induced a slight decrease in fat mass (FM) while a PPARγ agonist increased BW and FM commensurate with increased food consumption. The reduction in BW and food intake after cotreatment with PPARα and δ agonists appeared to be synergistic. GW4148, a PPARpan agonist, induced a significant and sustained reduction in BW and FM similar to an efficacious dose of rimonabant, an antiobesity compound.