Mechanisms responsible for enhanced fatty acid utilization by perfused hearts from type 2 diabetic db/db mice
Mechanisms responsible for enhanced fatty acid utilization by perfused hearts from type 2 diabetic db/db mice
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DOI：
10.1080/13813450701422617
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发表时间：
2007-04-01
影响因子：
3
通讯作者：
Severson, D. L.
中科院分区：
文献类型：
--
作者：
Carley, A. N.;Atkinson, L. L.;Severson, D. L.
本研究的目的是确定 2 型糖尿病 db/db 小鼠灌注心脏增强 FA 利用率（氧化和酯化）的生化机制。 db/db 心脏中脂肪酸转运蛋白 FAT/CD36 和 FABPpm 的质膜含量升高。还检查了可能导致 FA 氧化速率升高的线粒体机制。 db/db 心脏线粒体中的肉碱棕榈酰转移酶 1 活性没有变化，对丙二酰辅酶 A 抑制的敏感性也没有变化。在 db/db 心脏中，丙二酰辅酶 A 含量升高，AMP 激酶活性降低，这与 FA 氧化速率升高的心脏中的预期相反。 db/db 心脏线粒体中解偶联蛋白 3 的表达没有变化。因此，db/db 心脏中 FA 利用率的提高很可能是由于 FA 转运蛋白质膜含量增加导致 FA 摄取增加所致；所检查的线粒体机制不会导致 db/db 心脏中观察到的 FA 氧化升高。
The aim of this study was to determine the biochemical mechanism(s) responsible for enhanced FA utilization (oxidation and esterification) by perfused hearts from type 2 diabetic db/db mice. The plasma membrane content of fatty acid transporters FAT/CD36 and FABPpm was elevated in db/db hearts. Mitochondrial mechanisms that could contribute to elevated rates of FA oxidation were also examined. Carnitine palmitoyl transferase-1 activity was unchanged in mitochondria from db/db hearts, and sensitivity to inhibition by malonyl-CoA was unchanged. Malonyl-CoA content was elevated and AMP kinase activity was decreased in db/db hearts, opposite to what would be expected in hearts exhibiting elevated rates of FA oxidation. Uncoupling protein-3 expression was unchanged in mitochondria from db/db hearts. Therefore, enhanced FA utilization in db/db hearts is most likely due to increased FA uptake caused by increased plasma membrane content of FA transporters; the mitochondrial mechanisms examined do not contribute to elevated FA oxidation observed in db/db hearts.