Activation of peroxisome proliferator-activated receptor (PPAR) , , and 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 PPAR agonists. Herein we report the effects of selective PPAR agonists (GW9578, a PPAR agonist, GW0742, a PPAR agonist, GW7845, a PPAR agonist), combination of PPAR and agonists, and PPARpan (PPAR) 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. PPAR or PPAR agonist treatment induced a slight decrease in fat mass (FM) while a PPAR agonist increased BW and FM commensurate with increased food consumption. The reduction in BW and food intake after cotreatment with PPAR and 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. GW9135, a PPARpan agonist with weak activity at PPAR, induced weight loss initially followed by rebound weight gain reaching vehicle control levels by the end of the experiment. We conclude that PPAR and PPAR activations are critical to effective weight loss induction. These results suggest that the PPARpan compounds may be expected to maintain the beneficial insulin sensitization effects of a PPAR agonist while either maintaining weight or producing weight loss.