Effects Of Exercise On Association Of PGC1 With MEF2 In Skeletal Muscle Of Different Genotypic Mice Of AMPK

The peroxisome proliferators-activated receptor-y coactivator-1 (PGC1) is a nuclear transcriptional coactivator, which was discovered in recent years. It plays an important role in regulating glucose and lipid metabolism. Studies have found that, PGC1/MEF2 binding will affect the amount of the transcriptional regulation of MEF2, thereby regulating the GLUT4 gene and protein expression, but the exact mechanisms remain unclear.Purpose:To explore the role of AMPK in regulating the exercise induced PGC1 nuclear protein expression, PGC1 associated with MEF2 in three types of AMPKa 2 genetic mice after four weeks endurance training. Further explore the possible signaling pathways of GLUT4 expression.Methods:Two months old of C57BL/6J wild-type(WT) mice(n=20), a 2-AMPK over-expression(OE) mice(n=20)and a 2-AMPK whole-body knockout(KO) mice(n=20) were randomly subdivided into control groups and exercise groups. After four weeks of treadmill running(12m/min, lh/day), the association of PGC1 with MEF2 in nucleus of quadriceps femoris muscle was measured by co-immunoprecipitation, nucleus PGC1 protein expressions were measured by western blot.Results:1) Over-expression of the AMPKα2 isoform heightened the training-induced increase in nuclear PGC1 content and PGC1 associated with MEF2, while the training-induced increases of nuclear PGC1 content and PGC1 associated with MEF2 were normal in a 2-KO muscles despite the reduced AMPK signaling, suggest that AMPK activity during exercise is required, though not indispensable, for expression of PGC1 and PGC1 associated with MEF2.2) After four weeks of endurance training, the nuclear PGC1 content and PGC1 associated with MEF2 were significantly higher than control groups, suggest that exercise training can activate PGC1 expression and increase PGC1/MEF2 association.. Conclutions:(1)Four weeks'endurance training induced increase of association of PGC1 with MEF2 and PGC1 nucleus content in skeletal muscle of three genetic types of mice;(2)Comparing to WT mice, the effect that four weeks'endurance training resulted in increase of nucleus PGC1 expression and PGC1 accossion with MEF had strengthened in skeletal muscle of OE mice; (3)Comparing to WT mice, the effects that four weeks' endurance training resulted in increase of PGC1 accossion with MEF2 and PGC1 nucleus expression were not be weakened in skeletal muscle of KO mice. There may be other pathways which regulatead interaction of PGC1 and MEF2 during endurance training.