PPARα Protein Expression Was Increased by Four Weeks of Intermittent Hypoxic Training via AMPKα2-Dependent Manner in Mouse Skeletal Muscle.
Peroxisome proliferator-activated receptor α (PPARα) is critical for muscle endurance due to its role in the regulation of fatty acid oxidation. The 5'-AMP-activated protein kinase (AMPK) is an energy sensor in cells, but its role in PPARα regulation in vivo remains unknown. In this study, we examined PPARα expression in the skeletal muscle of AMPKα2 overexpression (OE), knockout (KO) and wild-type (WT) mice after four weeks of exercise under intermittent hypoxia. WT, OE and KO mice were used at 40 mice/strain and randomly subdivided into four subgroups: control (C), running (R), hypoxia (H), and running plus hypoxia (R+H) at 10 mice/group. The treadmill running was performed at the speed of 12 m/min, 60 min/day with a slope of 0 degree for four weeks. The hypoxia treatment was performed in daytime with normobaric hypoxia (11.20% oxygen, 8 hours/day). In the R+H group, the treadmill running was conducted in the hypoxic condition. AMPKα2, phosphor-AMPKα (p-AMPKα) (Thr172), nuclear PPARα proteins were measured by Western blot and the medium chain acyl coenzyme A dehydrogenase (MCAD) mRNA, the key enzyme for fatty acid oxidation and one of the PPARα target genes, was also measured in skeletal muscles after the interventions. The results showed that nuclear PPARα protein was significantly increased by R+H in WT muscles, the increase was enhanced by 41% (p<0.01) in OE mice, but was reduced by 33% (p<0.01) in KO mice. The MCAD mRNA expression was increased after four weeks of R+H intervention. The change in MCAD mRNA followed a similar trend as that of PPARα protein in OE and KO mice. Our data suggest that the increase in nuclear PPARα protein by four-week exercise training under the intermittent hypoxia was dependent on AMPK activation.
Division of Exercise Biochemistry, Institute of Sports Science, Beijing Sport University, China.
Ge
G
Li
School of Health and Wellbeing, Faculty of Health, Engineering, and Sciences, University of Southern Queensland, Australia.
Jianxiong
J
Wang
Pennington Biomedical Research Center, Louisiana State University, Louisiana, United States of America.
Jianping
J
Ye
Key Laboratory of Exercise and Physical Fitness (Beijing Sport University), Ministry of Education of the People's Republic of China.
Yimin
Y
Zhang
Division of Exercise Biochemistry, Institute of Sports Science, Beijing Sport University, China.
Ying
Y
Zhang
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D042964:Acyl-CoA Dehydrogenase / Q000235:genetics*; D000818:Animals; D015687:Cell Hypoxia; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D047493:PPAR alpha / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012420:Running / Q000502:physiology*; D015854:Up-Regulation
D047493:PPAR alpha; D012333:RNA, Messenger; D042964:Acyl-CoA Dehydrogenase; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases; D010100:Oxygen