Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2S2, Canada.
Physiol Behav. 2013 Jun 13;118:165-70. doi: 10.1016/j.physbeh.2013.03.030. Epub 2013 May 13.
Fatty acid metabolism is an important pathway involved in the hypothalamus-mediated control of food intake. Previous studies using whole hypothalamic tissue lysates have shown that fatty acid metabolism plays a key role in ghrelin's effect on feeding. Here, we report site-specific effects of central ghrelin on fatty acid metabolism in two critical hypothalamic nuclei, the ventral medial nucleus (VMN) and the arcuate nucleus (Arc). Intracerebroventricular administration of ghrelin to rats activates AMP-activated protein kinase in both the VMN and the Arc, while ghrelin treatment has a site-specific effect on fatty acid metabolic pathways in these two nuclei. In the VMN, central ghrelin increases the phosphorylation level of ACC, indicating the decrease in activity, and decreases the level of malonyl-CoA (the product of ACC). Malonyl-CoA is an inhibitor of carnitine palmitoyltransferase-1 (CPT-1) that is a key enzyme in mitochondrial fatty acid oxidation. Consistent with this action of malonyl-CoA on CPT-1, central ghrelin treatment increases the activity of CPT-1 in the VMN. In contrast, in the Arc, neither malonyl-CoA level nor CPT-1 activity is affected following central ghrelin. Taken together, our data suggest ghrelin exerts differential effects on fatty acid metabolic pathways in the VMN and the Arc.
脂肪酸代谢是下丘脑介导的摄食控制途径中的一个重要途径。以前使用整个下丘脑组织裂解物的研究表明，脂肪酸代谢在 ghrelin 对摄食的影响中起着关键作用。在这里，我们报告了中央 ghrelin 对两个关键下丘脑核（腹内侧核 (VMN) 和弓状核 (Arc)）中脂肪酸代谢的特定部位的影响。向大鼠侧脑室给予 ghrelin 可激活 VMN 和 Arc 中的 AMP 激活的蛋白激酶，而 ghrelin 处理对这两个核中的脂肪酸代谢途径具有特定的影响。在 VMN 中，中央 ghrelin 增加 ACC 的磷酸化水平，表明活性降低，并降低丙二酰辅酶 A（ACC 的产物）的水平。丙二酰辅酶 A 是肉碱棕榈酰基转移酶-1（CPT-1）的抑制剂，CPT-1 是线粒体脂肪酸氧化的关键酶。丙二酰辅酶 A 对 CPT-1 的这种作用一致，中央 ghrelin 处理增加了 VMN 中的 CPT-1 活性。相比之下，在 Arc 中，中央 ghrelin 处理后丙二酰辅酶 A 水平或 CPT-1 活性均不受影响。总之，我们的数据表明 ghrelin 对 VMN 和 Arc 中的脂肪酸代谢途径产生了不同的影响。
