Metabolic Remodeling during Liver Regeneration
Metabolic Remodeling during Liver Regeneration
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DOI：
10.1016/j.devcel.2018.09.020
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发表时间：
2018-11-19
影响因子：
11.8
通讯作者：
Kaldis, Philipp
中科院分区：
文献类型：
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作者：
Caldez, Matias J.;Van Hul, Noemi;Kaldis, Philipp
肝病与肝细胞分裂能力下降有关。此外，细胞代谢对于组织稳态和再生是重要的。由于代谢变化是肝脏疾病的标志，我们研究了代谢和细胞分裂之间的联系。我们使用整合的转录组学和代谢组学分析与先进的功能性氧化还原体内成像相结合，确定了肝再生不同阶段的总体代谢变化。我们的数据表明，在再生过程中阻断肝细胞分裂会导致线粒体功能障碍和氧化途径的下调。这导致氧化还原比增加和丙氨酸转氨酶活性亢进，从而在线粒体功能受损时允许从丙酮酸产生丙氨酸和α-酮戊二酸。我们的数据表明，在肝再生过程中，细胞分裂导致肝脏代谢重塑。此外，我们证明，肝细胞配备了灵活的代谢机制，能够动态适应组织再生过程中的变化。
Liver disease is linked to a decreased capacity of hepatocytes to divide. In addition, cellular metabolism is important for tissue homeostasis and regeneration. Since metabolic changes are a hallmark of liver disease, we investigated the connections between metabolism and cell division. We determined global metabolic changes at different stages of liver regeneration using a combination of integrated transcriptomic and metabolomic analyses with advanced functional redox in vivo imaging. Our data indicate that blocking hepatocyte division during regeneration leads to mitochondrial dysfunction and downregulation of oxidative pathways. This resulted in an increased redox ratio and hyperactivity of alanine transaminase allowing the production of alanine and alpha-ketoglutarate from pyruvate when mitochondrial functions are impaired. Our data suggests that during liver regeneration, cell division leads to hepatic metabolic remodeling. Moreover, we demonstrate that hepatocytes are equipped with a flexible metabolic machinery able to adapt dynamically to changes during tissue regeneration.