Requirement of hepatic pyruvate carboxylase during fasting, high fat and ketogenic diet

Pyruvate has two major fates upon entry into mitochondria, the oxidative decarboxylation to acetyl-CoA or the biotin-dependent carboxylation to oxaloacetate via pyruvate carboxylase (Pcx). Here we have generated mice with a liver specific knockout of Pcx to understand its role in hepatic mitochondrial metabolism under disparate physiological states including a 24 hour fast, as well as ketogenic and high fat diets. These data ultimately show the requirement of Pcx-mediated anapleorsis in the liver under disparate metabolic conditions. RNA-seq on liver tissue from 9wk old male wild-type and Pcx liver-specific knockout mice fasted for 24 hours.丙酮酸进入线粒体后存在两条主要代谢去路：一是经氧化脱羧生成乙酰辅酶A（acetyl-CoA），二是经依赖生物素的羧化反应，在丙酮酸羧化酶（pyruvate carboxylase, Pcx）催化下生成草酰乙酸（oxaloacetate）。本研究构建了Pcx肝脏特异性敲除小鼠，以探究其在多种不同生理状态下的肝脏线粒体代谢功能，所涉状态包括24小时禁食、生酮饮食及高脂饮食。本研究最终证实，在各类代谢条件下，肝脏中Pcx介导的回补反应（anapleorsis）均为必需过程。本研究对禁食24小时的9周龄雄性野生型小鼠及Pcx肝脏特异性敲除小鼠的肝脏组织开展了RNA测序（RNA-seq）。