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Chunk #37 — 3. Gluconeogenesis — 3.2. Gluconeogenesis from Lactate/Pyruvate

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Role of PPARα in Hepatic Carbohydrate Metabolism.
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Most studies mainly observed metabolic alterations in PPARα −/− mice in starved conditions [3, 18–24], whereas fed PPARα −/− mice had normal blood glucose [18, 19, 21, 23]. In a study performed by Atherton et al., however, metabolic alterations were also observed in fed PPARα −/− mice [54]. Here, metabolic profiling of several PPARα −/− tissues was performed via 1H-NMR spectroscopy and MS. Important metabolic differences were detected in all tissues, but in particular in liver. Liver of PPARα −/− mice contained profoundly decreased levels of glucose, several amino acids including glutamine and alanine, and increased levels of lactate. The combined presence of lower glucose and higher lactate content confirms impaired gluconeogenesis from lactate in PPARα −/− mice. This demonstrates that a failure to express PPARα results in perturbed balance between glycolysis, TCA cycle and gluconeogenesis [54].