Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle

Sebastian Beck Jørgensen, Jørgen Wojtaszewski, Benoit Viollet, Fabrizio Andreelli, Jesper Bratz Birk, Ylva Hellsten, Peter Schjerling, Sophie Vaulont, P. Darrell Neufer, Erik A. Richter, Henriette Pilegaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

244 Citationer (Scopus)

Abstract

We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body a2- and a1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmill running (90 min), and in recovery. Running increased a1-AMPK kinase activity, phosphorylation (P) of AMPK, and acetyl-CoA carboxylase (ACC)ß in a2-WT and a2-KO muscles and increased a2-AMPK kinase activity in a2-WT. In a2-KO muscles, AMPK-P and ACCß-P were markedly lower compared with a2-WT. However, in a1-WT and a1-KO muscles, AMPK-P and ACCß-P levels were identical at rest and increased similarly during exercise in the two genotypes. The a2-KO decreased peroxisome-proliferator-activated receptor ¿ coactivator (PGC)-1a, uncoupling protein-3 (UCP3), and hexokinase II (HKII) transcription at rest but did not affect exercise-induced transcription. Exercise increased the mRNA content of PGC-1a, Forkhead box class O (FOXO)1, HKII, and pyruvate dehydrogenase kinase 4 (PDK4) similarly in a2-WT and a2-KO mice, whereas glucose transporter GLUT 4, carnitine palmitoyltransferase 1 (CPTI), lipoprotein lipase, and UCP3 mRNA were unchanged by exercise in both genotypes. CPTI mRNA was lower in a2-KO muscles than in a2-WT muscles at all time-points. In a1-WT and a1-KO muscles, running increased the mRNA content of PGC-1a and FOXO1 similarly. The a2-KO was associated with lower muscle adenosine 5'-triphosphate content, and the inosine monophosphate content increased substantially at the end of exercise only in a2-KO muscles. In addition, subcutaneous injection of 5-aminoimidazole-4-carboxamide-1-ß-4-ribofuranoside (AICAR) increased the mRNA content of PGC-1a, HKII, FOXO1, PDK4, and UCP3, and a2-KO abolished the AICAR-induced increases in PGC-1a and HKII mRNA. In conclusion, KO of the a2- but not the a1-AMPK isoform markedly diminished AMPK activation during running. Nevertheless, exercise-induced activation of the investigated genes in mouse skeletal muscle was not impaired in a1- or a2-AMPK KO muscles. Although it cannot be ruled out that activation of the remaining a-isoform is sufficient to increase gene activation during exercise, the present data do not support an essential role of AMPK in regulating exercise-induced gene activation in skeletal muscle.
OriginalsprogEngelsk
TidsskriftThe FASEB Journal
Vol/bind19
Udgave nummer9
Sider (fra-til)1146-1148
Antal sider3
ISSN0892-6638
DOI
StatusUdgivet - 2005

Bibliografisk note

PUF 2005 5200 033

Citationsformater