PUBLICATION

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

Authors

Chen, Z., He, M., Wang, H., Li, X., Qin, R., Ye, D., Zhai, X., Zhu, J., Zhang, Q., Hu, P., Shui, G., Sun, Y.

ID

ZDB-PUB-241114-26

Date

2024

Source

Nature communications 15: 97699769 (Journal)

Registered Authors

He, Mudan, Sun, Yonghua, Ye, Ding

Keywords

none

MeSH Terms

Docosahexaenoic Acids*/metabolism
Zebrafish Proteins*/genetics
Zebrafish Proteins*/metabolism
Zebrafish*/embryology
Zebrafish*/metabolism
Intestinal Mucosa/metabolism
Lipid Metabolism
Embryo, Nonmammalian/metabolism
Gene Expression Regulation, Developmental
Embryonic Development
Animals
Egg Yolk/metabolism
Pancreas, Exocrine/metabolism
Larva/growth & development
Larva/metabolism
Intestines*/embryology

PubMed

39528516 Full text @ Nat. Commun.

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.

Genes / Markers

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