is determined by pyruvate dehydrogenase kinase 4 (PDK4), which phosphorylates and inactivates pyruvate dehydrogenase (PDH), the mitochondrial enzyme needed to convert pyruvate to acetyl-coenzyme A (acetyl-CoA) (Figure 2). The latter can enter the tricarboxylic acid (TCA) cycle for energy production but can also be used to build fatty acids for energy storage (Figure 1). When PDH is inactive, pyruvate cannot enter the mitochondria and will be metabolized to lactate, in order to regain NAD+ units. Transcription of PDK4 is stimulated by PPARα and glucocorticoids during fasting and is suppressed by insulin [29].
