Enhancing hepatic mitochondrial fatty acid oxidation stimulates eating in food-deprived mice.
Enhancing hepatic mitochondrial fatty acid oxidation stimulates eating in food-deprived mice.
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增强肝线粒体脂肪酸氧化可刺激食物匮乏小鼠的进食。
DOI：
10.1152/ajpregu.00279.2014
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Morral,Núria
中科院分区：
文献类型：
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作者：
Mansouri,Abdelhak;Pacheco-López,Gustavo;Ramachandran,Deepti;Arnold,Myrtha;Leitner,Claudia;Prip-Buus,Carina;Langhans,Wolfgang;Morral,Núria
肝脂肪酸氧化（FAO）长期以来被认为与饮食控制有关。然而，肝脏粮农组织变化与食物摄入量变化之间存在因果关系的直接证据仍然缺乏。在这里，我们测试了通过腺病毒介导的线粒体FAO肉碱棕榈酰基转移酶1A （CPT1mt）关键调控酶突变形式的表达增加肝脏FAO是否会影响小鼠的进食和代谢，CPT1mt具有活性，但对丙二酰辅酶a的抑制不敏感。CPT1mt表达增加肝细胞CPT1蛋白水平。这导致禁食cpt1mt表达小鼠的循环酮体水平增加，表明肝脏FAO增加。这些小鼠在食物剥夺4小时后，在累积食物摄入量、能量消耗或呼吸商方面没有表现出任何显著变化。然而，在24小时的食物剥夺后，表达cpt1mt的小鼠表现出增加的食物摄入量。因此，肝脏中CPT1mt的表达增加了肝脏的FAO能力，但不抑制进食。相反，它甚至可能在长时间的食物剥夺后刺激进食。这些数据不支持肝脏中粮农组织的增加会减少食物摄入量的假设。
Hepatic fatty acid oxidation (FAO) has long been implicated in the control of eating. Nevertheless, direct evidence for a causal relationship between changes in hepatic FAO and changes in food intake is still missing. Here we tested whether increasing hepatic FAO via adenovirus-mediated expression of a mutated form of the key regulatory enzyme of mitochondrial FAO carnitine palmitoyltransferase 1A (CPT1mt), which is active but insensitive to inhibition by malonyl-CoA, affects eating and metabolism in mice. CPT1mt expression increased hepatocellular CPT1 protein levels. This resulted in an increase in circulating ketone body levels in fasted CPT1mt-expressing mice, suggesting an increase in hepatic FAO. These mice did not show any significant changes in cumulative food intake, energy expenditure, or respiratory quotient after 4-h food deprivation. After 24-h food deprivation, however, the CPT1mt-expressing mice displayed increased food intake. Thus expression of CPT1mt in the liver increases hepatic FAO capacity, but does not inhibit eating. Rather, it may even stimulate eating after prolonged food deprivation. These data do not support the hypothesis that an increase in hepatic FAO decreases food intake.