肠道DHA-PA-PG轴通过调节母体沉积的蛋黄脂质的使用来促进消化器官的扩张-动脉网

Intestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids

Nature 等信源发布 2024-11-12 11:54

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AbstractAlthough the metabolism of yolk lipids such as docosahexaenoic acid (DHA) is pivotal for embryonic development, the underlying mechanism remains elusive. Here we find that the zebrafish hydroxysteroid (17-β) dehydrogenase 12a (hsd17b12a), which encodes an intestinal epithelial-specific enzyme, is essential for the biosynthesis of long-chain polyunsaturated fatty acids in primitive intestine of larval fish.

摘要尽管卵黄脂质（如二十二碳六烯酸（DHA））的代谢对于胚胎发育至关重要，但其潜在机制仍然难以捉摸。。

The deficiency of hsd17b12a leads to severe developmental defects in the primitive intestine and exocrine pancreas. Mechanistically, hsd17b12a deficiency interrupts DHA synthesis from essential fatty acids derived from yolk-deposited triglycerides, and consequently disrupts the intestinal DHA-phosphatidic acid (PA)-phosphatidylglycerol (PG) axis.

hsd17b12a的缺乏会导致原始肠和外分泌胰腺的严重发育缺陷。从机理上讲，hsd17b12a缺乏会中断来自蛋黄沉积的甘油三酯的必需脂肪酸的DHA合成，从而破坏肠道DHA-磷脂酸（PA）-磷脂酰甘油（PG）轴。

This ultimately results in developmental defects of digestive organs, primarily driven by ferroptosis. Our findings indicate that the DHA-PA-PG axis in the primitive intestine facilitates the uptake of yolk lipids and promotes the expansion of digestive organs, thereby uncovering a mechanism through which DHA regulates embryonic development..

这最终导致消化器官的发育缺陷，主要由ferroptosis驱动。。。

IntroductionThe yolk sac stores a large amount of maternal material accumulated during oogenesis, and serves as a nutrient source for embryonic development in both viviparous and oviparous vertebrates1. The metabolism of maternal materials plays an important role in embryonic development2. Unlike viviparous embryos, oviparous embryos depend entirely on yolk nutrients, highlighting the importance of the absorption and utilization of yolk nutrients for their embryonic development3.

引言卵黄囊储存了卵子发生过程中积累的大量母体物质，是胎生和卵生脊椎动物胚胎发育的营养来源1。。与胎生胚胎不同，卵子胚胎完全依赖卵黄营养素，突出了卵黄营养素的吸收和利用对其胚胎发育的重要性3。

Zebrafish, as oviparous organisms, depend solely on a single yolk for nutrition until the endogenous-to-exogenous nutrient source transition (eeNST), which mainly occurs at 5 days post-fertilization (5 dpf)4. In zebrafish, the yolk syncytial layer (YSL) hydrolyzes lipids to release fatty acids and produces lipoproteins that export lipids to the developing embryos until exogenous nutrients are absorbed5.

斑马鱼作为卵生生物，在内源营养源向外源营养源转化（eENT）之前，仅依赖单个卵黄进行营养，这主要发生在受精后5天（5 dpf）4。在斑马鱼中，卵黄合胞体层（YSL）水解脂质释放脂肪酸，并产生脂蛋白，将脂质输出到发育中的胚胎，直到外源营养被吸收5。

Previous studies also suggest that the primitive intestine is involved in the absorption of yolk lipids during embryonic development. For instance, lipid droplets were detected in the intestinal epithelial cells of sea bass during the lecithotrophic period6, and yolk-deposited fatty acids could be transported to the primitive intestine, and participate in lipid synthesis of zebrafish7.

先前的研究还表明，原始肠道参与胚胎发育过程中卵黄脂质的吸收。例如，在卵磷脂营养期间，在鲈鱼的肠上皮细胞中检测到脂滴6，卵黄沉积的脂肪酸可以转运到原始肠道，并参与斑马鱼的脂质合成7。

Dietary phosphatidylcholines (PCs) have been shown to accelerate the metabolism of triglycerides (TAGs) in the intestinal epithelium8. Nevertheless, the regulation of yolk lipid absorption by the primitive intestine has yet to be investigated.Phospholipids (PLs), including phosphatidic acids (PAs), phosphatidylglycerols (PGs), and PCs, can be distinguished based on the variations in the sn-1 and sn-2-linked fatty acid (FA) composition9.

膳食磷脂酰胆碱（PC）已被证明可加速肠上皮细胞中甘油三酯（TAG）的代谢8。然而，尚未研究原始肠道对卵黄脂质吸收的调节。磷脂（PLs），包括磷脂酸（PA），磷脂酰甘油（PGs）和PC，可以根据sn-1和sn-2连接脂肪酸（FA）组成的变化来区分9。

Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) are prefe.

饱和脂肪酸（SFAs）和单不饱和脂肪酸（MUFA）是首选。

Data availability

数据可用性

The sequence data that support the findings of this study have been deposited in the Genome Sequence Archive at the National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (CRA018363 [https://ngdc.cncb.ac.cn/gsa/search?searchTerm=CRA018363], CRA018331, and CRA018335) are publicly accessible at https://ngdc.cncb.ac.cn/gsa.

支持这项研究结果的序列数据已保存在中国国家生物信息中心/中国科学院北京基因组研究所国家基因组数据中心的基因组序列档案中（CRA018363[https://ngdc.cncb.ac.cn/gsa/search?searchTerm=CRA018363]，CRA018331和CRA018335）可在https://ngdc.cncb.ac.cn/gsa.

The lipidomics data are provided in Supplementary Data 3. Public bulk RNA-seq data are available in the GSA database under the accession numbers CRA005219 and CRA005220. The remaining data are available within the Article, Supplementary Information or Source data file. Source data are provided with this paper..

脂质组学数据在补充数据3中提供。GSA数据库中提供了公共批量RNA-seq数据，登录号为CRA005219和CRA005220。其余数据可在文章，补充信息或源数据文件中找到。本文提供了源数据。。

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We would like to thank Kuoyu Li and Luyuan Pan at the China Zebrafish Resource Center, National Aquatic Biological Resource Center (CZRC, NABRC, http://zfish.cn) for raising the zebrafish, Zhixian Qiao, Xiaocui Chai, Fang Zhou, Yuan Xiao, and Zhenfei Xing at the Analysis and Testing Center, Institute of Hydrobiology, Chinese Academy of Sciences, for their assistance with experiments.

我们要感谢中国斑马鱼资源中心，国家水生生物资源中心（CZRC，NABRC，http://zfish.cn)。

This work was funded by the National Natural Science Foundation of China (32025037), Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB0730300), National Key R&D Program of China (2023YFD2401603), Ministry of Agriculture and Rural Affairs (NK2022010207), Natural Science Foundation of Wuhan, Science and Technology Special Fund of Hainan Province (ZDYF2024XDNY256), and the Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture (CAS) to Y.S., and by the National Natural Science Foundation of China (grant No 32273134) and the Youth Innovation Promotion Association CAS (grant No.

这项工作由国家自然科学基金（32025037）、中国科学院战略重点研究计划（XDB0730300）、国家重点研发计划（2023YFD2401603）、农业和农村事务部（NK2022010207）、武汉市自然科学基金、海南省科学技术专项基金（ZDYF2024XDNY256）和Y.S育种生物技术与可持续水产养殖（CAS）重点实验室以及国家自然科学基金（批准号32273134）和中国科学院青年创新促进会（批准号：。

2023353) to M.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author informationAuthors and AffiliationsKey Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, Institute of Hydrobiology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Wuhan, 430072, ChinaZhengfang Che.

2023353）给M.H。资助者在研究设计，数据收集和分析，决定发表或准备手稿方面没有任何作用。作者信息作者和附属机构育种生物技术与可持续水产养殖实验室，湖北洪山实验室，中国科学院种子设计创新研究院水生生物研究所，武汉，430072，中国郑方车。

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PubMed Google ScholarContributionsZ.C. designed the research, performed experiments, analyzed data, and wrote the manuscript. M.H., H.W., X.L., R.Q., D.Y., X.Z., J.Z., and Q.Z. provided assistance with experiments. P.H. provided assistance with single-cell RNA-seq analyses. G.S.

PubMed谷歌学术贡献。C、。M、 H.，H.W.，X.L.，R.Q.，D.Y.，X.Z.，J.Z。和Q.Z.为实验提供了帮助。P、 H.为单细胞RNA-seq分析提供了帮助。G、 S。

provided assistance with lipidomic analyses. Y.S. designed the research, analyzed data, wrote and revised the manuscript.Corresponding authorCorrespondence to.

提供了脂质组学分析的帮助。Y、美国设计了这项研究，分析了数据，撰写并修改了手稿。对应作者对应。

Yonghua Sun.Ethics declarations

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Reprints and permissionsAbout this articleCite this articleChen, Z., He, M., Wang, H. et al. Intestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids.

转载和许可本文引用本文Chen，Z.，He，M.，Wang，H。等人。肠道DHA-PA-PG轴通过介导母体沉积的卵黄脂质的使用来促进消化器官的扩张。

Nat Commun 15, 9769 (2024). https://doi.org/10.1038/s41467-024-54258-2Download citationReceived: 30 January 2024Accepted: 01 November 2024Published: 12 November 2024DOI: https://doi.org/10.1038/s41467-024-54258-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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