Leucine stimulates PPARβ/δ-dependent mitochondrial biogenesis and oxidative metabolism with enhanced GLUT4 content and glucose uptake in myotubes

Working hypotheses of mechanisms governing leucine-induced metabolism in myotubes. Leucine stimulates Akt and protein synthesis resulting in increased ATP demands. Increased energy demands stimulate regulators of metabolism including AMPK, PPARβ/δ, and PGC-1α leading to increased oxidative metabolism, mitochondrial biogenesis, and GLUT4 content. Elevated GLUT4 content promotes increased glucose uptake to support rising energy needs. Augmented energy uptake promotes simultaneous substrate oxidation and storage (in-part through increased PPARγ) leading to increased cellular lipid content. Leucine may alter energy availability by stimulating substrate oxidation, substrate/lipid storage, and protein synthesis.280