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Intestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids
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Journal Article
Intestinal DHA-PA-PG axis promotes digestive organ expansion by mediating usage of maternally deposited yolk lipids
2024
Overview
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.
Lipid utilization from the yolk sac plays a crucial role in embryonic development. Here, Chen et al. generate
hsd17b12a
mutant zebrafish and discover that a docosahexaenoic acid (DHA)-phosphatidic acid (PA)-phosphatidylglycerol (PG) (DHA-PA-PG) axis facilitates the uptake of yolk lipids and promotes the expansion of digestive organs.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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/ Animals
/ Defects
/ Docosahexaenoic Acids - metabolism
/ Embryo, Nonmammalian - metabolism
/ Gene Expression Regulation, Developmental
/ Humanities and Social Sciences
/ Intestinal Mucosa - metabolism
/ Larva - growth & development
/ Lipids
/ Organs
/ Pancreas, Exocrine - metabolism
/ Science
/ Yolk
/ Yolk sac
