dc.contributor.authorDing, Jun
dc.contributor.authorLoizides-Mangold, Ursula
dc.contributor.authorRando, Gianpaolo
dc.contributor.authorZoete, Vincent
dc.contributor.authorMichielin, Olivier
dc.contributor.authorReddy, Janardan K.
dc.contributor.authorWahli, Walter
dc.contributor.authorRiezman, Howard
dc.contributor.authorThorens, Bernard
dc.identifier.citationDing, J., Loizides-Mangold, U., Rando, G., Zoete, V., Michielin, O., Reddy, J. K., et al. (2013). The peroxisomal enzyme L-PBE is required to prevent the dietary toxicity of medium-chain Fatty acids. Cell reports, 5(1), 248-258.en_US
dc.description.abstractSpecific 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.en_US
dc.relation.ispartofseriesCell reportsen_US
dc.rights© 2013 The Authors. This paper was published in Cell Reports and is made available as an electronic reprint (preprint) with permission of The Authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1016/j.celrep.2013.08.032].  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.en_US
dc.titleThe peroxisomal enzyme L-PBE is required to prevent the dietary toxicity of medium-chain Fatty acidsen_US
dc.typeJournal Article
dc.contributor.schoolLee Kong Chian School of Medicine
dc.description.versionPublished versionen_US

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