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 toward 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 KO mice (Hep-). Mice were fed chow diets with a wide coverage of protein contents; , 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- 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 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- 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- mice and consequently the spontaneous physical activity was markedly reduced in GDH KO mice. These data highlight the central role of liver GDH in the energy balance adaptation to dietary proteins.

中文翻译：

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膳食蛋白质负荷影响能量和氮平衡，需要肝脏谷氨酸脱氢酶来维持身体活动


向肝脏提供氨基酸有助于糖异生，但需要安全处理氨基。线粒体酶谷氨酸脱氢酶 (GDH) 通过将过量的氨基酸脱氨以促进尿素生成并防止高氨血症，是肝氨解毒的核心。本研究调查了对照小鼠和肝脏特异性 GDH KO 小鼠 (Hep-) 对饮食蛋白质摄入变化的早期适应性反应。给小鼠喂食蛋白质含量广泛的食物； ，次优 10%，标准 20%，超过最优 30%，以及高 45% 蛋白质饮食；每4天更换一次。在组织收集和分析之前，在量热室中评估小鼠的代谢适应。 Hep-小鼠表现出丙氨酸诱导的糖异生受损和持续性高氨血症。不同饮食没有显着改变肝裂解物中 GDH 的表达和活性。然而，对冷冻保存的组织切片进行氧化还原敏感测定后发现，喂食高蛋白饮食的小鼠肝脏 GDH 活性较高。在同一切片系列上，免疫组织化学提供了 GDH 表达的相应图谱。量热室的余弦分析表明，Hep 小鼠的食物摄入和能量消耗的昼夜节律发生了改变。在对照小鼠中，当饮食改为高蛋白质含量时，能量消耗从碳水化合物转向氨基酸氧化。这种转变在 Hep- 小鼠中受到损害，因此 GDH KO 小鼠的自发体力活动显着减少。这些数据强调了肝脏 GDH 在适应膳食蛋白质的能量平衡中的核心作用。