Requirement for the heart-type fatty acid binding protein in cardiac fatty acid utilization
Requirement for the heart-type fatty acid binding protein in cardiac fatty acid utilization
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DOI：
10.1096/fasebj.13.8.805
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发表时间：
1999-05-01
期刊：
影响因子：
4.8
通讯作者：
Clark, AJ
中科院分区：
文献类型：
--
作者：
Binas, B;Danneberg, H;Clark, AJ
非酶胞质脂肪酸结合蛋白（FABPs）在许多脂肪酸代谢率高的动物组织中大量表达。尽管这些蛋白质与游离长链脂肪酸（LCFAs）的运输和对LCFA毒性的保护有关，但没有证明任何FABP的生理作用。我们在这里报道，缺乏心脏型FABP （H-FABP）的小鼠表现出外周（非肝脏、非脂肪）LCFA利用的严重缺陷，在这些小鼠中，心脏不能有效地吸收血浆LCFAs，这通常是它的主要燃料，并转换为葡萄糖的使用。葡萄糖、乳酸和β -羟基丁酸与外周LCFA利用降低、碳水化合物使用加剧和肝脏LCFA氧化增加一致；这些变化在有利于LCFA氧化的条件下最为明显。然而，H-FABP缺乏只是不完全补偿，引起急性运动不耐受，并在老年时引起局部心脏肥厚。这些数据证实了H-FABP在心脏细胞内脂质转运和燃料选择中的需求，以及在代谢稳态中的主要作用。这种新的动物模型对于研究外周LCFA对心功能、胰岛素敏感性和血压的意义尤其有用。
Nonenzymatic cytosolic fatty acid binding proteins (FABPs) are abundantly expressed in many animal tissues with high rates of fatty acid metabolism. No physiological role has been demonstrated for any FABP, although these proteins have been implicated in transport of free long-chain fatty acids (LCFAs) and protection against LCFA toxicity, We report here that mice lacking heart-type FABP (H-FABP) exhibit a severe defect of peripheral (nonhepatic, non-fat) LCFA utilization, In these mice, the heart is unable to efficiently take up plasma LCFAs, which are normally its main fuel, and switches to glucose usage, Altered plasma levels of LCFAs, glucose, lactate and beta-hydroxybutyrate are consistent with depressed peripheral LCFA utilization, intensified carbohydrate usage, and increased hepatic LCFA oxidation; these changes are most pronounced under conditions favoring LCFA oxidation. H-FABP deficiency is only incompletely compensated, however, causing acute exercise intolerance and, at old age, a localized cardiac hypertrophy. These data establish a requirement for H-FABP in cardiac intracellular lipid transport and fuel selection and a major role in metabolic homeostasis. This new animal model should be particularly useful for investigating the significance of peripheral LCFA utilization for heart function, insulin sensitivity, and blood pressure.