Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake
Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake
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DOI：
10.1073/pnas.0809255105
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发表时间：
2008-11-04
影响因子：
11.1
通讯作者：
Lane, M. Daniel
中科院分区：
文献类型：
--
作者：
Cha, Seung Hun;Wolfgang, Michael;Lane, M. Daniel
美国人的饮食，尤其是青少年的饮食，含有高能量含量的可口食物和大量的高果糖甜味剂。这些因素被认为是肥胖流行和胰岛素抵抗的原因之一。以往的研究表明，葡萄糖的中枢代谢抑制了下丘脑AMP-激酶/丙二酰辅酶A信号系统介导的食物摄取。与葡萄糖不同，中央管理的果糖增加了食物的摄入量。实验结果表明，中枢果糖代谢启动较快会消耗下丘脑ATP水平，而葡萄糖代谢调节较慢会提高下丘脑ATP水平。与对[ATP]/[AMP]比率的影响一致，果糖增加下丘脑AMP激酶的磷酸化/激活，导致乙酰辅酶A羧基酶的磷酸化/失活，而葡萄糖的作用相反。中枢给予果糖引起的变化降低了下丘脑丙二酰辅酶A水平，从而增加了食物摄入量。这些发现解释了果糖对食物摄入量的矛盾影响，并支持丙二酰辅酶A假说。
The American diet, especially that of adolescents, contains highly palatable foods of high-energy content and large amounts of high-fructose sweeteners. These factors are believed to contribute to the obesity epidemic and insulin resistance. Previous investigations revealed that the central metabolism of glucose suppresses food intake mediated by the hypothalamic AMP-kinase/malonyl-CoA signaling system. Unlike glucose, centrally administered fructose increases food intake. Evidence presented herein indicates that the more rapid initial steps of central fructose metabolism deplete hypothalamic ATP level, whereas the slower regulated steps of glucose metabolism elevate hypothalamic ATP level. Consistent with effects on the [ATP]/[AMP] ratio, fructose increases phosphorylation/activation of hypothalamic AMP kinase causing phosphorylation/inactivation of acetyl-CoA carboxylase, whereas glucose has the inverse effects. The changes provoked by central fructose administration reduce hypothalamic malonyl-CoA level and thereby increase food intake. These findings explain the paradoxical fructose effect on food intake and lend credence to the malonyl-CoA hypothesis.