The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
The Peroxisomal Enzyme L-PBE Is Required to Prevent the Dietary Toxicity of Medium-Chain Fatty Acids
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DOI：
10.1016/j.celrep.2013.08.032
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发表时间：
2013-10-01
期刊：
影响因子：
8.8
通讯作者：
Thorens, Bernard
中科院分区：
文献类型：
--
作者：
Ding, Jun;Loizides-Mangold, Ursula;Thorens, Bernard
特定的代谢途径被不同的营养物质激活，以使有机体适应可用的资源。尽管这些机制是必不可少的，但它们的定义并不完整。在这里，我们报告了椰子油中所含的中链脂肪酸，这是饮食脂肪的主要来源，诱导肝脏omega氧化基因Cyp4a10和Cyp4a14增加二羧酸的产生。此外，它们通过过氧化物酶体增殖物激活受体(PPAR)α和PPARγ激活所有的omega和β-氧化途径，这是一个激活循环，通常由过氧化体酶L-pBE降解二羧酸来控制。事实上，喂食椰子油的L-pBE(-/-)小鼠体内二羧酸过量积累，激活了所有脂肪酸氧化途径，导致肝脏炎症、纤维化和死亡。因此，正确的二羧酸动态平衡是调节摄入的中链脂肪酸有效利用的一种手段，而它的解除调节体现了新陈代谢受损和炎症之间的复杂关系。
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 omega-oxidation genes Cyp4a10 and Cyp4a14 to increase the production of dicarboxylic fatty acids. Furthermore, these activate all omega- and beta-oxidation pathways through peroxisome proliferator activated receptor (PPAR) alpha and PPAR gamma, 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.