Overexpression of leptin reduces the ratio of glycolytic to oxidative enzymatic activities without changing muscle fiber types in mouse skeletal muscle.

Increased spontaneous locomotive activity and oxygen consumption have been reported in transgenic mice overexpressing leptin in the liver. In the present study, we examined whether the overexpression of leptin altered glycolytic and oxidative metabolic enzymatic activities as well as the composition of myosin heavy chain (MHC) isoforms in skeletal muscle. Enzymatic activities of lactate dehydrogenase (LDH) and citrate synthase (CS) were quantified in gastrocnemius muscle (GAS) and the red portion of tibialis anterior muscle (TA) from leptin transgenic (Tg) mice and non-Tg mice. The composition of MHC isoforms was measured in soleus muscle (SOL) and extensor digitorum longus muscle (EDL) from the two groups. In red TA, LDH-to-CS ratio was significantly lower in Tg than in non-Tg (p=0.014), whereas no significant change was observed in GAS. The composition of MHC isoforms was not significantly different in SOL or EDL between Tg and non-Tg groups. Our data indicate that chronic overexpression of leptin reduces the ratio of glycolytic to oxidative capacity without changing muscle fiber types particularly in red muscles. This metabolic change may contribute to the increased spontaneous locomotive activity and oxygen consumption in Tg mice reported previously.