Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
Open accessAbstract
Polyunsaturated fatty acids (PUFAs) in phospholipids affect the physical properties of membranes, but it is unclear which biological processes are influenced by their regulation. For example, the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis remain largely unknown. Here, we show that the lack of lysophosphatidylcholine acyltransferase 3 (LPCAT3) leads to drastic reductions in membrane arachidonate levels, and that LPCAT3-deficient mice are neonatally lethal due to an extensive triacylglycerol (TG) accumulation and dysfunction in enterocytes. We found that high levels of PUFAs in membranes enable TGs to locally cluster in high density, and that this clustering promotes efficient TG transfer. We propose a model of local arachidonate enrichment by LPCAT3 to generate a distinct pool of TG in membranes, which is required for normal directionality of TG transfer and lipoprotein assembly in the liver and enterocytes.
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High phospholipid unsaturation may modify membrane physical properties and augment release of cholesteryl ester and triacylglycerol-containing vesicles from the endoplasmic reticulum.
“High PL unsaturation may modify membrane physical properties and augment release of CE and TAG-containing vesicles from ER45,46.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [45]
The Introduction and Discussion (page numbers unavailable) say PUFA-rich phospholipids make membranes more flexible and propose that this helps triglyceride transport. The Results report greater triglyceride clustering and MTP-mediated transfer with PUFA-rich membranes. The paper does not establish enhanced release of cholesteryl ester–containing vesicles from the ER, or directly show vesicle release as the mechanism. (LLM, conf=0.86)
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- Authors
- Hashidate-Yoshida, T., Harayama, T., Hishikawa, D., Morimoto, R., Hamano, F., Tokuoka, S. M., Eto, M., Tamura-Nakano, M., Yanobu-Takanashi, R., Mukumoto, Y., Kiyonari, H., Okamura, T., Kita, Y., Shindou, H., & Shimizu, T.
- Affiliations
- Department of Lipid Signaling, National Center for Global Health and Medicine, Tokyo, Japan
- National Center for Global Health and Medicine (JP)
- The University of Tokyo (JP)
- Communal Laboratory, National Center for Global Health and Medicine, Tokyo, Japan
- Department of Laboratory Animal Medicine, National Center for Global Health and Medicine, Tokyo, Japan
- Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan
- Japan Science and Technology Agency (JP)
- Corresponding author
- Shimizu, Takao
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-04-21
- Volume
- 4
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4436788
- OpenAlex
- W1976336399
- Cited by
- 270
- References
- 64
- Citations by year
- 2026: 31 · 2025: 32 · 2024: 40 · 2023: 26 · 2022: 31 · 2021: 26 · 2020: 17 · 2019: 17 · 2018: 21 · 2017: 13 · 2016: 12 · 2015: 4
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (JSPS) (24229003, 26460380, 26860202, 26870879)
- Takeda Science Foundation (Special Research grant 2013)
- National Center for Global Health and Medicine (24-001,25-201, 26A105)
- Japan Science and Technology Agency (JST) (CREST)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- LPCAT3, lysophosphatidylcholine acyltransferase, arachidonic acid, phospholipid membranes, polyunsaturated fatty acids, enterocytes, neonatal lethality, lipoprotein assembly, membrane lipid remodeling, hepatic lipoprotein secretion
- MeSH terms
- Animals, Cell Membrane, Fatty Acids, Fatty Acids, Unsaturated, Liver, 1-Acylglycerophosphocholine O-Acyltransferase, Phospholipids, Triglycerides, Arachidonic Acid, Cell Culture Techniques, Enterocytes, Mice
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