Proteomics identifies the developmental regulation of HKDC1 in liver of pigs and mice.

Proteomics identifies the developmental regulation of HKDC1 in liver of pigs and mice.
复制标题

蛋白质组学鉴定了 HKDC1 在猪和小鼠肝脏中的发育调节。

DOI:
10.1152/ajpregu.00253.2022
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发表时间:
2023
期刊:
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子:
--
通讯作者:
Wolfgang,MichaelJ
Wolfgang,MichaelJ
中科院分区:
--
文献类型:
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作者:
Martinez-Garza,Ursula;Choi,Joseph;Scafidi,Susana;Wolfgang,MichaelJ

文献摘要

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在围产期,独特的代谢适应支持快速生长的能量需求。为了深入了解围产期的适应,对出生后7天的约克夏猪和成年猪的肝脏进行了定量蛋白质组学的比较。这些数据揭示了肝功能代谢控制的差异,包括脂肪和碳水化合物代谢途径的显着变化。新生儿肝脏表现出脂肪分解代谢和糖异生中蛋白质的丰富,伴随着肝脏肉碱和乙酰肉碱水平的升高。糖激酶是与新生和成年猪相比差异最大的几种蛋白质,包括半乳糖激酶1(Galk1)、酮己糖激酶(KHK)、己糖激酶1(HK1)和己糖激酶4(GCK)。有趣的是,新发现的第五种与孕妇血糖紊乱相关的己糖激酶区1(HKDC1)在猪和小鼠出生前和围产期的肝脏中高度丰富,并在出生后整个发育过程中持续下降。通过Western印迹和mRNA表达证实了这些变化。这些数据为多种哺乳动物从围产期向成年期过渡过程中肝脏的发育和代谢适应提供了新的见解。
During the perinatal period, unique metabolic adaptations support energetic requirements for rapid growth. To gain insight into perinatal adaptations, quantitative proteomics was performed comparing the livers of Yorkshire pigs at postnatalday 7and adult. These data revealed differences in the metabolic control of liver function including significant changes in lipid and carbohydrate metabolic pathways. Newborn livers showed an enrichment of proteins in lipid catabolism and gluconeogenesis concomitant with elevated liver carnitine and acylcarnitines levels. Sugar kinases were some of the most dramatically differentially enriched proteins compared with neonatal and adult pigs including galactokinase 1 (Galk1), ketohexokinase (KHK), hexokinase 1 (HK1), and hexokinase 4 (GCK). Interestingly, hexokinase domain containing 1 (HKDC1), a newly identified fifth hexokinase associated with glucose disturbances in pregnant women, was highly enriched in the liver during the prenatal and perinatal periods and continuously declined throughout postnatal development in pigs and mice. These changes were confirmed via Western blot and mRNA expression. These data provide new insights into the developmental and metabolic adaptations in the liver during the transition from the perinatal period to adulthood in multiple mammalian species.