Fatty acyl-chain remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
- National Center for Global Health and Medicine, Japan
- National Center for Global Health and Medicine, Switzerland
- The University of Tokyo, Japan
- RIKEN Center for Developmental Biology, Japan
Abstract
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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Author details
Reviewing Editor
- Ben Cravatt, The Scripps Research Institute, United States
Ethics
Animal experimentation: All animal experiments were approved by and performed in accordance with the guidelines of the Animal Research Committee of National Center for Global Health and Medicine (12053, 13009, 14045), and the animal experimentation committee of the University of Tokyo (H09-144, P08-042).
Version history
- Received: January 8, 2015
- Accepted: April 19, 2015
- Accepted Manuscript published: April 21, 2015 (version 1)
- Version of Record published: May 19, 2015 (version 2)
Copyright
© 2015, Hashidate-Yoshida et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Fatty acyl-chain remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
eLife 4:e06328.
https://doi.org/10.7554/eLife.06328
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