Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production
Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production
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DOI：
10.1038/nm873
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发表时间：
2003-06-01
期刊：
影响因子：
82.9
通讯作者：
Rossetti, L
中科院分区：
文献类型：
--
作者：
Obici, S;Feng, ZH;Rossetti, L
酶肉毒碱棕榈酰转移酶-1（CPT 1）调节长链脂肪酸（LCFA）进入线粒体，其中LCFA进行β-氧化。为了研究脂质中枢代谢调节能量平衡的机制，我们选择性地减少了下丘脑中的脂质氧化。我们通过给大鼠施用含有核酶的质粒来降低CPT 1的活性，该质粒专门设计用于降低这种酶的表达，或者通过将其活性的药理学抑制剂注入第三脑室来降低CPT 1的活性。无论是遗传或生物化学抑制下丘脑CPT 1活性是足以大大减少食物摄入量和内源性葡萄糖的生产。这些结果表明，在选择性下丘脑神经元的脂质氧化速率的变化信号的营养供应到下丘脑，这反过来又调制的外源性和内源性输入的营养物质进入循环。
The enzyme carnitine palmitoyltransferase-1 (CPT1) regulates long-chain fatty acid (LCFA) entry into mitochondria, where the LCFAs undergo beta-oxidation. To investigate the mechanism(s) by which central metabolism of lipids can modulate energy balance, we selectively reduced lipid oxidation in the hypothalamus. We decreased the activity of CPT1 by administering to rats a ribozyme-containing plasmid designed specifically to decrease the expression of this enzyme or by infusing pharmacological inhibitors of its activity into the third cerebral ventricle. Either genetic or biochemical inhibition of hypothalamic CPT1 activity was sufficient to substantially diminish food intake and endogenous glucose production. These results indicated that changes in the rate of lipid oxidation in selective hypothalamic neurons signaled nutrient availability to the hypothalamus, which in turn modulated the exogenous and endogenous inputs of nutrients into the circulation.