哺乳期醛缩酶C缺乏的生理后果。

IF 2.6 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
PLoS ONE Pub Date : 2024-12-12 eCollection Date: 2024-01-01 DOI:10.1371/journal.pone.0315719
James A Votava, Jing Fan, Brian W Parks
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引用次数: 0

摘要

哺乳期乳腺强烈诱导新生脂肪生成(DNL),以支持乳汁中脂肪酸、甘油三酯和胆固醇的合成。在单胃动物中,葡萄糖是泌乳乳腺中 DNL 的主要底物,必须有效地吸收和处理葡萄糖,为 DNL 提供细胞乙酰-CoA。除了 DNL 途径中的酶之外,糖酵解酶醛醇酶 C(Aldoc)在乳腺泌乳期间也会出现转录上调和高表达,这表明 Aldoc 在泌乳中发挥作用。Aldoc 也是固醇调节元件结合蛋白 1 和 2(Srebp1 和 Srebp2)的转录靶标,后者可转录调节 DNL 途径中的酶,最近的研究表明它可调节血浆胆固醇和甘油三酯。在这里,我们利用全身 Aldoc 基因敲除小鼠研究了 Aldoc 在泌乳中的作用。我们的研究结果表明,Aldoc 对泌乳有显著影响,Aldoc-/-母鼠哺育的幼鼠体重下降。乳汁的生化分析表明,Aldoc-/-母鼠的乳汁中半乳糖含量明显较高,乳糖和胆固醇含量较低。对 Aldoc-/- 母鼠乳汁脂质的质谱分析表明,含有中链和长链脂肪酸的甘油三酯含量明显较低,这对泌乳有直接影响,因为这些甘油三酯是人类乳腺中由葡萄糖合成的主要甘油三酯。总之,我们的研究结果为 Aldoc 在哺乳期乳腺乳糖和脂质合成中的作用提供了功能性证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Physiological consequences of Aldolase C deficiency during lactation.

Physiological consequences of Aldolase C deficiency during lactation.

Physiological consequences of Aldolase C deficiency during lactation.

Physiological consequences of Aldolase C deficiency during lactation.

The lactating mammary gland strongly induces de novo lipogenesis (DNL) to support the synthesis of fatty acids, triglycerides, and cholesterol found within milk. In monogastric species, glucose is a major substrate utilized for DNL within the lactating mammary gland and must be efficiently taken up and processed to supply cytosolic acetyl-CoA for DNL. Along with the enzymes of the DNL pathway, the glycolytic enzyme, Aldolase C (Aldoc), is transcriptionally upregulated and is highly expressed during lactation in the mammary gland, suggesting a role for Aldoc in lactation. Aldoc is also a transcriptional target of the sterol regulatory element binding proteins 1 and 2 (Srebp1 and Srebp2), which transcriptionally regulate enzymes within the DNL pathway and has recently been shown to regulate plasma cholesterol and triglycerides. Here, we investigate the role of Aldoc in lactation, by utilizing a whole-body Aldoc knockout mouse. Our results demonstrate that Aldoc has a significant impact on lactation, whereby pups nursing from Aldoc-/- dams have reduced body weight. Biochemical analysis of milk identified that milk from Aldoc-/- dams have significantly higher galactose, lower lactose, and cholesterol content. Mass spectrometry analysis of milk lipids from Aldoc-/- dams revealed significantly lower quantities of medium and long chain fatty acid containing triglycerides, which has direct implications on lactation as these are the predominant triglycerides synthesized from glucose in human mammary gland. Overall, our results provide functional evidence for the contribution of Aldoc in mammary gland lactose and lipid synthesis during lactation.

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来源期刊
PLoS ONE
PLoS ONE 生物-生物学
CiteScore
6.20
自引率
5.40%
发文量
14242
审稿时长
3.7 months
期刊介绍: PLOS ONE is an international, peer-reviewed, open-access, online publication. PLOS ONE welcomes reports on primary research from any scientific discipline. It provides: * Open-access—freely accessible online, authors retain copyright * Fast publication times * Peer review by expert, practicing researchers * Post-publication tools to indicate quality and impact * Community-based dialogue on articles * Worldwide media coverage
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