Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
J Cardiovasc Pharmacol. 2011 Jan;57(1):103-13. doi: 10.1097/FJC.0b013e31820014f9.
Leptin directly acts on peripheral tissues and alters energy metabolism in obese mice. It also has acute beneficial effects on these tissues via its hypothalamic action. However, it is not clear what effect chronic intracerebroventrical (ICV) leptin administration has on cardiac energy metabolism. We examined the effects of chronic ICV leptin on glucose and fatty acid metabolism in isolated working hearts from high-fat-fed and low-fat-fed mice. Mice were fed a high-fat (60% calories from fat) or low-fat (10% calories from fat) diet for 8 weeks before ICV leptin (5 [mu]g/d) for 7 days. In low-fat-fed mice, leptin increased glucose oxidation rates in isolated working hearts when compared with control [203 +/- 21 vs. 793 +/- 93 nmol[middle dot](g dry weight)-1[middle dot]min-1]. In high-fat-fed mice leptin inhibited fatty acid oxidation [476 +/- 73 vs. 251 +/- 38 nmol[middle dot](g[middle dot]dry[middle dot]wt)-1[middle dot]min-1]. The increase in glucose oxidation in low-fat-fed mice was accompanied by increased pyruvate dehydrogenase activity. In high-fat-fed mice, leptin increased cardiac malonyl coenzyme A levels, secondary to a decrease in malonyl coenzyme A decarboxylase expression. These results suggest that ICV leptin alters cardiac energy metabolism opposite to its peripheral effects and that these effects differ depending on energy substrate supply to the mice.
瘦素直接作用于外周组织，改变肥胖小鼠的能量代谢。它通过下丘脑作用对这些组织也有急性有益影响。然而，尚不清楚慢性脑室内（ICV）给予瘦素对心脏能量代谢有什么影响。我们研究了慢性 ICV 瘦素对高脂和低脂喂养小鼠分离工作心脏中葡萄糖和脂肪酸代谢的影响。小鼠高脂（60%热量来自脂肪）或低脂（10%热量来自脂肪）喂养 8 周后，给予 ICV 瘦素（5μg/d）7 天。在低脂喂养的小鼠中，与对照相比，瘦素增加了分离工作心脏中的葡萄糖氧化率[203±21 比 793±93 nmol（g 干重）-1 min-1]。在高脂喂养的小鼠中，瘦素抑制脂肪酸氧化[476±73 比 251±38 nmol（g 干重）-1 min-1]。低脂喂养小鼠中葡萄糖氧化的增加伴随着丙酮酸脱氢酶活性的增加。在高脂喂养的小鼠中，瘦素增加了心脏丙二酰辅酶 A 水平，这是由于丙二酰辅酶 A 脱羧酶表达减少所致。这些结果表明，ICV 瘦素改变了心脏能量代谢，与外周作用相反，这些作用因小鼠能量底物的供应而异。
