Dietary protein load affects the energy and nitrogen balance requiring liver glutamate dehydrogenase to maintain physical activity

Article Article scientifique Article Dietary protein load affects the energy and nitrogen balance requiring liver glutamate dehydrogenase to maintain physical activity eng 2024-07 author Luczkowska Karolina 843142 author Zhou Yan 931387 author Ramos Lobo Angela 0000-0003-1062-0708 974628 Département de physiologie cellulaire et métabolisme (PHYME) author Brun Thierry 0000-0002-1659-4283 24644 Structure enseignement (ENSI) author Maechler Pierre 0000-0002-2005-1433 76515 Département de physiologie cellulaire et métabolisme (PHYME) 107473 10.1016/j.jbc.2024.107473 38879007 0021-9258 https://linkinghub.elsevier.com/retrieve/pii/S0021925824019744 Provision of amino acids to the liver is instrumental for gluconeogenesis while it requires safe disposal of the amino group. The mitochondrial enzyme glutamate dehydrogenase (GDH) is central for hepatic ammonia detoxification by deaminating excessive amino acids towards ureagenesis and preventing hyperammonemia. The present study investigated the early adaptive responses to changes in dietary protein intake in control mice and liver-specific GDH knockout mice (Hep-Glud1-/-). Mice were fed chow diets with a wide coverage of protein contents; i.e. suboptimal 10%, standard 20%, over optimal 30%, and high 45% protein diets; switched every 4 days. Metabolic adaptations of the mice were assessed in calorimetric chambers before tissue collection and analyses. Hep-Glud1-/- mice exhibited impaired alanine induced gluconeogenesis and constitutive hyperammonemia. The expression and activity of GDH in liver lysates were not significantly changed by the different diets. However, applying an in situ redox-sensitive assay on cryopreserved tissue sections revealed higher hepatic GDH activity in mice fed the high-protein diets. On the same section series, immunohistochemistry provided corresponding mapping of the GDH expression. Cosinor analysis from calorimetric chambers showed that the circadian rhythm of food intake and energy expenditure was altered in Hep-Glud1-/- mice. In control mice, energy expenditure shifted from carbohydrate to amino acid oxidation when diet was switched to high protein content. This shift was impaired in Hep-Glud1-/- mice and consequently the spontaneous physical activity was markedly reduced in GDH knockout mice. These data highlight the central role of liver GDH in the energy balance adaptation to dietary proteins. Ammonia Dietary protein Gluconeogenesis Glutamate dehydrogenase Liver Dewey 612 Swiss National Science Foundation An integrated multi-organ analysis of glutamate dehydrogenase 192486 CH Projects 134 Département de physiologie cellulaire et métabolisme 21C false 402 Mitochondries et métabolisme énergétique 671 The Journal of biological chemistry 300 7 ba24876d-cd12-4f4b-ace1-7a357e0b5a9e Article (Published version) Public 2024-Luczkowska-JBC.pdf 5183607 application/pdf CC BY-4.0 ab1207cd49520af61d4964ec467cb000d55d284461192b2f12a42576d66fa3d8 cf6183d8-b69f-4580-b510-0d31dfb3571a Supplemental data Public 1-s2.0-S0021925824019744-mmc1.pdf 754281 application/pdf 4f5ec92cfe808fe48f8c852378eb149f94385fbbe691f41a6fd215ee9ee2fe14 openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Ramos Lobo, Angela

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