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

Article Article scientifique Article The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids eng 2013 author Ding Jun author Loizides-Mangold Ursula Elfriede 668364 Ursula Loizides-Mangold author Rando Gianpaolo 802397 author Zoete Vincent author Michielin Olivier 0000-0003-4926-6355 903944 author Reddy Janardan K. author Wahli Walter 544127 author Riezman Howard 134430 author Thorens Bernard 639542 248-258 10.1016/j.celrep.2013.08.032 2211-1247 https://linkinghub.elsevier.com/retrieve/pii/S2211124713004737 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. Dewey 540 39 Département de biochimie 144 false Cell Reports 5 1 a86a5e26-6f71-470d-81df-c18bc92f817e Article (Published version) Public ThePeroxisomal_HR_13.pdf 3078717 application/pdf openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids	Cell Reports			2013	285	137

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Rando, Gianpaolo