title: A metabolomic study of the PPARδ agonist GW501516 for enhancing running endurance in Kunming mice.
abstract: Exercise can increase peroxisome proliferator-activated receptor-δ (PPARδ) expression in skeletal muscle. PPARδ regulates muscle metabolism and reprograms muscle fibre types to enhance running endurance. This study utilized metabolomic profiling to examine the effects of GW501516, a PPARδ agonist, on running endurance in mice. While training alone increased the exhaustive running performance, GW501516 treatment enhanced running endurance and the proportion of succinate dehydrogenase (SDH)-positive muscle fibres in both trained and untrained mice. Furthermore, increased levels of intermediate metabolites and key enzymes in fatty acid oxidation pathways were observed following training and/or treatment. Training alone increased serum inositol, glucogenic amino acids, and branch chain amino acids. However, GW501516 increased serum galactose and β-hydroxybutyrate, independent of training. Additionally, GW501516 alone raised serum unsaturated fatty acid levels, especially polyunsaturated fatty acids, but levels increased even more when combined with training. These findings suggest that mechanisms behind enhanced running capacity are not identical for GW501516 and training. Training increases energy availability by promoting catabolism of proteins, and gluconeogenesis, whereas GW501516 enhances specific consumption of fatty acids and reducing glucose utilization.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: National Center of Biomedical Analysis, Beijing 100039, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Xinni
authors.initials: X
authors.lastname: Xie
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: National Center of Biomedical Analysis, Beijing 100039, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: National Center of Biomedical Analysis, Beijing 100039, China.
authors.forename: Fangting
authors.initials: F
authors.lastname: Dong
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D008297:Male; D055442:Metabolome / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D047494:PPAR delta / Q000819:agonists*; D058573:Performance-Enhancing Substances / Q000008:administration & dosage*; D010805:Physical Conditioning, Animal / Q000379:methods; D010807:Physical Endurance / Q000187:drug effects / Q000502:physiology*; D020543:Proteome / Q000378:metabolism; D012420:Running / Q000502:physiology*; D013844:Thiazoles / Q000008:administration & dosage*
chemical_list: C425931:GW 501516; D009124:Muscle Proteins; D047494:PPAR delta; D058573:Performance-Enhancing Substances; D020543:Proteome; D013844:Thiazoles