Belke D D, Wang L C, Lopaschuk G D
Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Biochim Biophys Acta. 1998 Mar 6;1391(1):25-36. doi: 10.1016/s0005-2760(97)00199-9.
Although mammalian hibernators rely on stored body fat as a source of energy, direct measurement of energy substrate preference in heart tissue during hibernation, as well as potential mechanisms controlling fatty acid oxidation has not been examined. In order to determine whether an increase in fatty acid utilization occurs during hibernation, glucose and palmitate oxidation were measured in isolated working hearts from hibernating and non-hibernating Richardson's ground Squirrels. Hearts were perfused at either 37 degrees or 5 degrees C with perfusate containing 11 mM [U-14C]glucose and 1.2 mM [9,10-3H]palmitate, which allowed for direct measurement of both glucose oxidation (14CO2 production) and fatty acid oxidation (3H2O production). The contribution of fatty acid oxidation as a source of citric acid cycle acetyl-CoA was significantly greater in hearts from hibernating animals, compared to hearts from non-hibernating animals. Since acetyl-CoA carboxylase (ACC) regulates cardiac fatty acid oxidation (producing malonyl-CoA, a potent inhibitor of mitochondrial fatty acid uptake), we measured the activity and expression of ACC in these hearts. ACC activity was significantly decreased in hibernating ground squirrels, regardless of whether ACC was assayed at 37 degrees or 5 degrees C. This decrease in activity could not be explained by a change in the activity of 5'AMP-activated protein kinase, which can phosphorylate and inhibit ACC. Rather, the expression of the 280 kDa isoform of ACC (which predominates in cardiac muscle) was decreased in hearts from hibernating squirrel hearts. This suggests that a down regulation of ACC expression occurs as an adaptation for the increased utilization of fatty acid in hearts of hibernating ground squirrels.
尽管哺乳动物冬眠者依靠储存的身体脂肪作为能量来源，但在冬眠期间心脏组织中能量底物偏好的直接测量以及控制脂肪酸氧化的潜在机制尚未得到研究。为了确定冬眠期间脂肪酸利用是否增加，我们测量了冬眠和非冬眠的理查森地松鼠离体工作心脏中的葡萄糖和棕榈酸氧化。心脏在37℃或5℃下用含有11mM [U-14C]葡萄糖和1.2mM [9,10-3H]棕榈酸的灌注液灌注，这使得能够直接测量葡萄糖氧化（14CO2产生）和脂肪酸氧化（3H2O产生）。与非冬眠动物的心脏相比，冬眠动物心脏中脂肪酸氧化作为柠檬酸循环乙酰辅酶A来源的贡献显著更大。由于乙酰辅酶A羧化酶（ACC）调节心脏脂肪酸氧化（产生丙二酰辅酶A，一种线粒体脂肪酸摄取的有效抑制剂），我们测量了这些心脏中ACC的活性和表达。无论在37℃还是5℃下测定ACC，冬眠地松鼠的ACC活性均显著降低。这种活性降低不能用5'AMP激活的蛋白激酶活性的变化来解释，5'AMP激活的蛋白激酶可以磷酸化并抑制ACC。相反，冬眠松鼠心脏中ACC的280kDa同工型（在心肌中占主导）的表达降低。这表明ACC表达的下调是冬眠地松鼠心脏中脂肪酸利用增加的一种适应性变化。
