The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids.

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Version: Final published version
Serval ID
serval:BIB_32435212F771
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids.
Journal
Cell Reports
Author(s)
Ding J., Loizides-Mangold U., Rando G., Zoete V., Michielin O., Reddy J.K., Wahli W., Riezman H., Thorens B.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
2013
Volume
5
Number
1
Pages
248-258
Language
english
Abstract
Specific metabolic pathways are activated by different nutrients to adapt the organism to available resources. Although essential, these mechanisms are incompletely defined. Here, we report that medium-chain fatty acids contained in coconut oil, a major source of dietary fat, induce the liver ω-oxidation genes Cyp4a10 and Cyp4a14 to increase the production of dicarboxylic fatty acids. Furthermore, these activate all ω- and β-oxidation pathways through peroxisome proliferator activated receptor (PPAR) α and PPARγ, an activation loop normally kept under control by dicarboxylic fatty acid degradation by the peroxisomal enzyme L-PBE. Indeed, L-pbe(-/-) mice fed coconut oil overaccumulate dicarboxylic fatty acids, which activate all fatty acid oxidation pathways and lead to liver inflammation, fibrosis, and death. Thus, the correct homeostasis of dicarboxylic fatty acids is a means to regulate the efficient utilization of ingested medium-chain fatty acids, and its deregulation exemplifies the intricate relationship between impaired metabolism and inflammation.
Pubmed
Web of science
Open Access
Yes
Create date
21/11/2013 11:56
Last modification date
20/08/2019 13:17
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