Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37204, USA.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37204, USA; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37204, USA.
Curr Biol. 2017 Nov 6;27(21):R1147-R1151. doi: 10.1016/j.cub.2017.09.019.
The liver is a critical hub for numerous physiological processes. These include macronutrient metabolism, blood volume regulation, immune system support, endocrine control of growth signaling pathways, lipid and cholesterol homeostasis, and the breakdown of xenobiotic compounds, including many current drugs. Processing, partitioning, and metabolism of macronutrients provide the energy needed to drive the aforementioned processes and are therefore among the liver's most critical functions. Moreover, the liver's capacities to store glucose in the form of glycogen, with feeding, and assemble glucose via the gluconeogenic pathway, in response to fasting, are critical. The liver oxidizes lipids, but can also package excess lipid for secretion to and storage in other tissues, such as adipose. Finally, the liver is a major handler of protein and amino acid metabolism as it is responsible for the majority of proteins secreted in the blood (whether based on mass or range of unique proteins), the processing of amino acids for energy, and disposal of nitrogenous waste from protein degradation in the form of urea metabolism. Over the course of evolution this array of hepatic functions has been consolidated in a single organ, the liver, which is conserved in all vertebrates. Developmentally, this organ arises as a result of a complex differentiation program that is initiated by exogenous signal gradients, cellular localization cues, and an intricate hierarchy of transcription factors. These processes that are fully developed in the mature liver are imperative for life. Liver failure from any number of sources (e.g. viral infection, overnutrition, or oncologic burden) is a global health problem. The goal of this primer is to concisely summarize hepatic functions with respect to macronutrient metabolism. Introducing concepts critical to liver development, organization, and physiology sets the stage for these functions and serves to orient the reader. It is important to emphasize that insight into hepatic pathologies and potential therapeutic avenues to treat these conditions requires an understanding of the development and physiology of specialized hepatic functions.
肝脏是许多生理过程的关键枢纽。这些过程包括：宏量营养素代谢、血容量调节、免疫系统支持、生长信号通路的内分泌控制、脂质和胆固醇稳态以及外源性化合物（包括许多当前药物）的分解。宏量营养素的加工、分配和代谢为驱动上述过程提供了所需的能量，因此是肝脏最重要的功能之一。此外，肝脏在进食时以糖原的形式储存葡萄糖、在禁食时通过糖异生途径合成葡萄糖的能力也至关重要。肝脏可以氧化脂质，但也可以将多余的脂质包装起来分泌到其他组织中储存，如脂肪组织。最后，肝脏是蛋白质和氨基酸代谢的主要处理者，因为它负责血液中大多数蛋白质（无论是基于质量还是独特蛋白质的范围）的分泌、氨基酸的能量加工以及蛋白质降解产生的含氮废物以尿素代谢的形式处理。在进化过程中，肝脏这一单一器官整合了这一系列的肝脏功能，所有脊椎动物都有肝脏。在发育过程中，这个器官是由外源性信号梯度、细胞定位线索和复杂的转录因子层次结构引发的复杂分化程序产生的。这些在成熟肝脏中完全发育的过程对生命至关重要。任何来源（如病毒感染、营养过剩或肿瘤负担）的肝衰竭都是全球性的健康问题。本入门指南的目的是简要总结肝脏在宏量营养素代谢方面的功能。引入对肝脏发育、组织和生理学至关重要的概念，为这些功能奠定了基础，并为读者提供了指导。需要强调的是，深入了解肝脏病理学和潜在的治疗这些疾病的方法需要了解肝脏特殊功能的发育和生理学。
