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

Author

Listed:
  • Zhengfang Chen

    (Chinese Academy of Sciences
    Hainan University
    University of Chinese Academy of Sciences)

  • Mudan He

    (Chinese Academy of Sciences)

  • Houpeng Wang

    (Chinese Academy of Sciences)

  • Xuehui Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ruirui Qin

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ding Ye

    (Chinese Academy of Sciences
    Hainan University
    University of Chinese Academy of Sciences)

  • Xue Zhai

    (Shanghai Ocean University)

  • Junwen Zhu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Quanqing Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Peng Hu

    (Shanghai Ocean University)

  • Guanghou Shui

    (Chinese Academy of Sciences)

  • Yonghua Sun

    (Chinese Academy of Sciences
    Hainan University
    University of Chinese Academy of Sciences)

Abstract

Although 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. 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. 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.

Suggested Citation

  • Zhengfang Chen & Mudan He & Houpeng Wang & Xuehui Li & Ruirui Qin & Ding Ye & Xue Zhai & Junwen Zhu & Quanqing Zhang & Peng Hu & Guanghou Shui & Yonghua Sun, 2024. "Intestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54258-2
    DOI: 10.1038/s41467-024-54258-2
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    References listed on IDEAS

    as
    1. Connor Ross & Thorsten E. Boroviak, 2020. "Origin and function of the yolk sac in primate embryogenesis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Qing Zhang & Deqiang Yao & Bing Rao & Liyan Jian & Yang Chen & Kexin Hu & Ying Xia & Shaobai Li & Yafeng Shen & An Qin & Jie Zhao & Lu Zhou & Ming Lei & Xian-Cheng Jiang & Yu Cao, 2021. "The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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