A metabolomic study of the PPARδ agonist GW501516 for enhancing running endurance in Kunming mice.
A metabolomic study of the PPARδ agonist GW501516 for enhancing running endurance in Kunming mice.
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DOI：
10.1038/srep09884
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发表时间：
2015-05-06
影响因子：
4.6
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Chen W;Gao R;Xie X;Zheng Z;Li H;Li S;Dong F;Wang L
运动可增加骨骼肌过氧化物酶体增殖物激活受体δ（PPARδ）的表达。PPARδ调节肌肉代谢，重新编程肌肉纤维类型，以增强跑步耐力。本研究利用代谢组学分析来检测GW 501516（一种PPARδ激动剂）对小鼠跑步耐力的影响。虽然单独训练增加了力竭跑的表现，但GW 501516治疗增强了训练和未训练小鼠的跑步耐力和琥珀酸脱氢酶（SDH）阳性肌纤维的比例。此外，在训练和/或治疗后观察到脂肪酸氧化途径中的中间代谢物和关键酶水平增加。单独训练增加血清肌醇、生糖氨基酸和分支链氨基酸。然而，GW 501516增加血清半乳糖和β-羟基丁酸，独立于训练。此外，单独使用GW 501516可提高血清不饱和脂肪酸水平，尤其是多不饱和脂肪酸，但与训练相结合时，其水平会增加更多。这些发现表明，GW 501516和训练增强跑步能力的机制并不相同。训练通过促进蛋白质的分解和代谢来增加能量的可用性，而GW 501516提高脂肪酸的特定消耗并减少葡萄糖的利用。
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.
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影响因子：
64.5
作者：
Narkar VA;Downes M;Yu RT;Embler E;Wang YX;Banayo E;Mihaylova MM;Nelson MC;Zou Y;Juguilon H;Kang H;Shaw RJ;Evans RM
通讯作者：
Evans RM
影响因子：
4.8
作者：
Mahoney, DJ;Parise, G;Tarnopolsky, MA
通讯作者：
Tarnopolsky, MA
影响因子：
4.4
作者：
Clarke, SD
通讯作者：
Clarke, SD
影响因子：
4.8
作者：
Luquet, S;Lopez-Soriano, J;Grimaldi, PA
通讯作者：
Grimaldi, PA
DOI：
10.1111/j.1439-0396.2004.00493.x
发表时间：
2004-04-01
影响因子：
2.7
作者：
Assenza, A;Bergero, D;Caola, G
通讯作者：
Caola, G