TY - JOUR
T1 - The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
AU - Ding, Jun
AU - Loizides-Mangold, Ursula
AU - Rando, Gianpaolo
AU - Zoete, Vincent
AU - Michielin, Olivier
AU - Reddy, Janardan K.
AU - Wahli, Walter
AU - Riezman, Howard
AU - Thorens, Bernard
N1 - Funding Information:
The authors would like to thank Catherine Moret and Marianne Carrard (Phenotyping and Metabolic Evaluation Facility of Center for Integrative Genomics) and Isabelle Riezman (University of Geneva) for technical assistance. This work was supported by grants 3100A0-113525 (B.T.) and 3100A0-128670 (HR) from the Swiss National Science Foundation, the Swiss SystemsX.ch initiative, LipidX-2008/011 (H.R. and B.T.), the European Union Sixth Framework Program on Hepatic and Adipose Tissue and Functions in the Metabolic Syndrome (EU-FP6 HEPADIP) to B.T., the NCCR Frontiers in Genetics (W.W. and B.T.), the National Centre of Competence in Research Chemical Biology (H.R.), and in part by National Institutes of Health grant DK083163 (to J.K.R.).
PY - 2013/10/17
Y1 - 2013/10/17
N2 - 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
AB - 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
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U2 - 10.1016/j.celrep.2013.08.032
DO - 10.1016/j.celrep.2013.08.032
M3 - Article
C2 - 24075987
AN - SCOPUS:84885835004
SN - 2211-1247
VL - 5
SP - 248
EP - 258
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -