Since the fasted PPARα −/− liver fails to induce fatty acid β-oxidation, ketone body synthesis is hampered and peripheral organs cannot be fueled with ketone bodies [3, 18, 19, 21, 25, 39]. Therefore, these organs solely rely on glycolytic consumption of glucose and increased amounts of lactate arise. However, since expression of key gluconeogenic genes and HGP are not increased in PPARα −/− mice compared with control mice [3, 20, 22, 35], this suggests that the PPARα −/− liver does not upregulate gluconeogenesis via compensatory mechanisms despite decreased systemic glucose levels and increased peripheral production of the gluconeogenic substrate lactate.
