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

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-oxi...

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Main Authors:	Jun Ding, Ursula Loizides-Mangold, Gianpaolo Rando, Vincent Zoete, Olivier Michielin, Janardan K. Reddy, Walter Wahli, Howard Riezman, Bernard Thorens
Format:	Article
Language:	English
Published:	Elsevier 2013-10-01
Series:	Cell Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124713004737

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spelling	doaj-0d40bfc9b50e49d0845a7686b93f6df22020-11-24T21:37:16ZengElsevierCell Reports2211-12472013-10-015124825810.1016/j.celrep.2013.08.032The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty AcidsJun Ding0Ursula Loizides-Mangold1Gianpaolo Rando2Vincent Zoete3Olivier Michielin4Janardan K. Reddy5Walter Wahli6Howard Riezman7Bernard Thorens8Center for Integrative Genomics, University of Lausanne, Lausanne 1015, SwitzerlandDepartment of Biochemistry, NCCR Chemical Biology, University of Geneva, 1211 Geneva, SwitzerlandCenter for Integrative Genomics, University of Lausanne, Lausanne 1015, SwitzerlandSwiss Institute for Bioinformatics, University of Lausanne, 1015 Lausanne, SwitzerlandSwiss Institute for Bioinformatics, University of Lausanne, 1015 Lausanne, SwitzerlandDepartment of Pathology, Northwestern University, Chicago, IL 60611, USACenter for Integrative Genomics, University of Lausanne, Lausanne 1015, SwitzerlandDepartment of Biochemistry, NCCR Chemical Biology, University of Geneva, 1211 Geneva, SwitzerlandCenter for Integrative Genomics, University of Lausanne, Lausanne 1015, Switzerland 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. http://www.sciencedirect.com/science/article/pii/S2211124713004737
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Jun Ding Ursula Loizides-Mangold Gianpaolo Rando Vincent Zoete Olivier Michielin Janardan K. Reddy Walter Wahli Howard Riezman Bernard Thorens
spellingShingle	Jun Ding Ursula Loizides-Mangold Gianpaolo Rando Vincent Zoete Olivier Michielin Janardan K. Reddy Walter Wahli Howard Riezman Bernard Thorens The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids Cell Reports
author_facet	Jun Ding Ursula Loizides-Mangold Gianpaolo Rando Vincent Zoete Olivier Michielin Janardan K. Reddy Walter Wahli Howard Riezman Bernard Thorens
author_sort	Jun Ding
title	The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
title_short	The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
title_full	The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
title_fullStr	The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
title_full_unstemmed	The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
title_sort	peroxisomal enzyme l-pbe is required to prevent the dietary toxicity of medium-chain fatty acids
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2013-10-01
description	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.
url	http://www.sciencedirect.com/science/article/pii/S2211124713004737
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The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids

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