Tfam overexpression has been shown to increase mitochondrial biogenesis and respiratory function (Ekstrand et al., 2004; Canugovi et al., 2010), but there is not clear how Tfam signals to the nucleus, and that a key factors associated with muscle adaptation are involved in Tfam overexpression by endurance exercise. The aim of this study was to identify the effects of Tfam expression by endurance exercise on AMPK, PPARβ/δ and PGC-1α that are associated with skeletal muscle adaptive response.
Mice were subjected to the forced swimming for 2 week or Tfam was electroporated in tibialis anterior (TA) muscle. To identify PPARβ/δ effect on Tfam, PPARβ/δ was electroporated in PGC-1α knockout mouse muscle. Mice Swimming for 2 wk result in an increase Tfam, PPARβ/δ and PGC-1α in TA muscle.
Endurance exercise raining group showed a significant higher expression of PPARβ/δ and PGC-1α in skeletal muscle. Tfam overexpression in mouse TA muscle induced in an increase AMP:ATP ratio, AMPK phosphorylation, PPARβ/δ and PGC-1α expression. PPARβ/δ overexpression in PGC-1α knockout muscle in mouse result in an increase Tfam expression.
Endurance exercise could be drive the activation of AMPK and PPARβ/δ (Fillmore et al., 2010; Koh et al., 2016). Our finding indicate that an increased Tfam expression by endurance exercise increases AMPK activation through controled AMP:ATP ratio that result in an increase PPARβ/δ and PGC-1α expression. These results indicate that Tfam can increase itself through AMPK-PPARβ/δ and/or PGC-1α axis.
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