Intestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids
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.
Authors
- Quanqing Zhang (ORCID: https://orcid.org/0000-0002-6400-8613)
- Houpeng Wang (ORCID: https://orcid.org/0000-0002-7462-6562)
- Zhengfang Chen
- Ruirui Qin
- Mudan He (ORCID: https://orcid.org/0000-0003-2018-9384)
- Guanghou Shui (ORCID: https://orcid.org/0000-0002-1621-9643)
- Xue Zhai
- Yonghua Sun (ORCID: https://orcid.org/0000-0001-9368-6969)
- Xuehui Li (ORCID: https://orcid.org/0000-0002-9644-2422)
- Junwen Zhu (ORCID: https://orcid.org/0009-0000-5554-445X)
- Ye Ding (ORCID: https://orcid.org/0000-0003-3460-1122)
- Peng Hu (ORCID: https://orcid.org/0000-0003-0173-3647)
Institutions
- Chinese Academy of Sciences (CN)
- Hainan University (CN)
- Institute of Hydrobiology (CN)
- Hainan Provincial Academy of Marine Fisheries and Aquaculture (CN)
- Institute of Genetics and Developmental Biology (CN)
- University of Chinese Academy of Sciences (CN)
- Shanghai Ocean University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1038/s41467-024-54258-2
- Citations
- 8
- Primary Topic
- Birth, Development, and Health
- Type
- article
- Field-Weighted Citation Impact
- 8.87
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Youth Innovation Promotion Association of the Chinese Academy of Sciences
- Institute of Hydrobiology
- Youth Innovation Promotion Association