d‐3‐Hydroxy‐n‐butyrate dehydrogenase (BDH1; EC 1.1.1.30), encoded by BDH1, catalyzes the reversible reduction of acetoacetate (AcAc) to 3‐hydroxybutyrate (3HB). BDH1 is the last enzyme of hepatic ketogenesis and the first enzyme of ketolysis. The hereditary deficiency of BDH1 has not yet been described in humans. To define the features of BDH1 deficiency in a mammalian model, we generated Bdh1‐deficient mice (Bdh1 KO mice). Under normal housing conditions, with unrestricted access to food, Bdh1 KO mice showed normal growth, appearance, behavior, and fertility. In contrast, fasting produced marked differences from controls. Although Bdh1 KO mice survive fasting for at least 48 hours, blood 3HB levels remained very low in Bdh1 KO mice, and despite AcAc levels moderately higher than in controls, total ketone body levels in Bdh1 KO mice were significantly lower than in wild‐type (WT) mice after 16, 24, and 48 hours fasting. Hepatic fat content at 24 hours of fasting was greater in Bdh1 KO than in WT mice. Systemic BDH1 deficiency was well tolerated under normal fed conditions but manifested during fasting with a marked increase in AcAc/3HB ratio and hepatic steatosis, indicating the importance of ketogenesis for lipid energy balance in the liver.

中文翻译：

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小鼠 3-羟基丁酸脱氢酶 (BDH1) 缺乏会导致禁食期间酮体水平低和脂肪肝。

d -3-羟基-正丁酸脱氢酶（BDH1；EC 1.1.1.30），由BDH1编码，催化乙酰乙酸（AcAc）可逆还原为 3-羟基丁酸（3HB）。BDH1是肝脏生酮的最后一个酶，也是酮解的第一个酶。尚未在人类中描述 BDH1 的遗传性缺陷。要定义在哺乳动物模型BDH1缺乏的功能，我们产生BDH1缺陷小鼠（BDH1 KO小鼠）。在正常的居住条件下，不受限制地获取食物，Bdh1 KO 小鼠显示出正常的生长、外观、行为和生育能力。相比之下，禁食与对照组产生了显着差异。虽然Bdh1KO小鼠存活下来禁食至少48小时，血3HB水平保持在非常低的BDH1 KO小鼠，尽管乙酰丙酮水平比对照，在总酮体水平适度较高BDH1 KO小鼠比野生型均显著降低（WT）禁食 16、24 和 48 小时后的小鼠。Bdh1 KO 小鼠禁食 24 小时的肝脏脂肪含量高于 WT 小鼠。全身性 BDH1 缺乏在正常进食条件下耐受良好，但在禁食期间表现为 AcAc/3HB 比率显着增加和肝脏脂肪变性，表明生酮对肝脏脂质能量平衡的重要性。