Premium
Effects of the PPARδ agonist GW501516 on exercise performance of mice
Author(s) -
Wolfram Swen,
Raederstorff Daniel,
Wyss Conrad,
Celio Marco,
Weber Peter
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a580-c
Subject(s) - agonist , placebo , endocrinology , medicine , treadmill , chemistry , receptor , skeletal muscle , peroxisome proliferator activated receptor , turnover , pharmacology , alternative medicine , management , pathology , economics
Background: Mice overexpressing peroxisome proliferator‐activated receptorδ (PPARδ) in skeletal muscle are characterized by reduced adiposity, enhanced skeletal muscle lipid oxidation, increased numbers of type I fibers and markedly prolonged running time on the treadmill. It was hypothesized that treatment with PPARδ agonists could increase exercise capacity. Methods: Male C57BL/6J mice on a high‐fat diet were randomized to receive GW501516 at 3, 10, or 30 mg/kg/day or placebo for 2 months. Two additional groups receiving GW501516 at 10 mg/kg/day or placebo were allowed to perform voluntary wheel running during the study. Body weight, body composition, glucose tolerance, voluntary wheel running activity and maximal exercise capacity on the treadmill were determined. Results: GW501516 decreased body weight and body fat and improved oral glucose tolerance in a dose‐dependent manner. Voluntary wheel running activity significantly decreased over time in mice receiving GW501516 at 10 mg/kg/day. Maximal exercise capacity was not altered by GW501516 in sedentary mice. In voluntarily running mice, GW501516 modestly decreased maximal exercise capacity on the treadmill compared to placebo, which could be a direct consequence of the reduced voluntary running activity. Conclusion: Treatment with the synthetic PPARδ agonist GW501516 for 2 months does not improve maximal exercise capacity in sedentary mice. Furthermore, voluntary wheel running activity was reduced in mice receiving GW501516 , which may have resulted in the observed decrease in treadmill exercise capacity.