Fasting regulates hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocortin in diabetic mice independent of changes in leptin or insulin
Fasting regulates hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocortin in diabetic mice independent of changes in leptin or insulin
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DOI：
10.1210/en.140.10.4551
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发表时间：
1999-10-01
期刊：
影响因子：
4.8
通讯作者：
Mobbs, CV
中科院分区：
文献类型：
--
作者：
Mizuno, TM;Makimura, H;Mobbs, CV
禁食增加下丘脑神经肽Y（NPY）和刺鼠相关肽（AGRP）信使RNA（mRNA）并减少下丘脑POMC mRNA，并且还以血浆瘦素、胰岛素和葡萄糖的减少为特征，其中每一种都涉及下丘脑基因表达的调节。为了进一步评估瘦素、胰岛素和葡萄糖在介导禁食效应中的作用，我们在随意进食和48小时禁食条件下检测了非糖尿病小鼠和链脲佐菌素（STZ）诱导的糖尿病小鼠下丘脑基因表达。在糖尿病和非糖尿病小鼠中，禁食刺激下丘脑NPY和AGRP mRNA，抑制下丘脑POMC mRNA和脂肪瘦素mRNA。然而，在糖尿病小鼠中，禁食对血浆瘦素和胰岛素没有影响，同时降低血糖，而在非糖尿病小鼠中，禁食降低血浆瘦素、胰岛素和血糖。此外，在非糖尿病禁食小鼠中，NPY和AGRP mRNA较高，POMC mRNA和血糖较低，比糖尿病自由进食小鼠，即使胰岛素和瘦素在这两组中相似。这些数据与以下假设一致：虽然瘦素和胰岛素调节下丘脑基因表达，但在低胰岛素和瘦素条件下，葡萄糖或其他因素可能对下丘脑和脂肪基因表达具有独立影响。
Fasting increases hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AGRP) messenger RNA (mRNA) and reduces hypothalamic POMC mRNA, and is also characterized by a reduction in plasma leptin, insulin, and glucose, each of which has been implicated in the regulation of hypothalamic gene expression. To further evaluate the roles of leptin, insulin, and glucose in mediating effects of fasting, we examined hypothalamic gene expression in nondiabetic and streptozotocin (STZ)-induced diabetic mice both under ad lib fed and 48-h fasted conditions. In both diabetic and nondiabetic mice, fasting stimulated hypothalamic NPY and AGRP mRNA and inhibited hypothalamic POMC mRNA and adipose leptin mRNA. However, in diabetic mice fasting had no effect on plasma leptin and insulin while decreasing plasma glucose, whereas in nondiabetic mice fasting decreased plasma leptin, insulin, and glucose. Furthermore, in nondiabetic fasted mice, NPY and AGRP mRNA were higher, and POMC mRNA and plasma glucose were lower, than in diabetic ad lib fed mice, even though insulin and leptin were similar in these two groups. These data are consistent with the hypothesis that although leptin and insulin regulate hypothalamic gene expression, glucose or other factors may have independent effects on hypothalamic and adipose gene expression under conditions of low insulin and leptin.