The hepatic vagus mediates fat-induced inhibition of diabetic hyperphagia
The hepatic vagus mediates fat-induced inhibition of diabetic hyperphagia
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DOI：
10.2337/diabetes.52.9.2321
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发表时间：
2003-09-01
期刊：
影响因子：
7.7
通讯作者：
Dallman, MF
中科院分区：
文献类型：
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作者：
la Fleur, SE;Ji, H;Dallman, MF
糖尿病大鼠摄入过多的高碳水化合物饮食，并改变了下丘脑神经肽 Y (NPY) 和促肾上腺皮质激素释放因子 (CRF)。相比之下，高脂肪饮食可将糖尿病患者的热量摄入降低至正常水平，这可以通过正常的下丘脑 NPY 和 CRF 含量反映出来。大脑如何感知饮食的这些变化尚不清楚。迄今为止，还没有荷尔蒙的变化可以解释这些饮食引起的热量摄入变化。我们测试了肝迷走神经的共同分支是否介导脂肪信号。我们以两种方式呈现脂肪。首先，除了正常的高碳水化合物饮食外，还给糖尿病和媒介物治疗的大鼠提供了一杯猪油。其次，我们将糖尿病大鼠从高碳水化合物饮食改为高脂肪饮食，没有选择。在链脲佐菌素治疗的大鼠中，两种方法均导致脂肪诱导的热量摄入抑制和下丘脑神经肽正常化至非糖尿病水平。引人注目的是，普通分支肝迷走神经切断术（与胃十二指肠迷走神经切断术不同）完全阻止了这些脂肪引起的变化。尽管肝能量状态的变化不能解释猪油引起的糖尿病大鼠的变化，但数据表明，常见的肝分支迷走神经切断术不会干扰肝能量状态。此外，没有糖尿病的普通分支肝迷走神经切断术会诱发肥胖指数。肝迷走神经功能异常（如糖尿病神经病变）可能导致糖尿病性肥胖。
Diabetic rats both overeat high-carbohydrate diet and have altered hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). In contrast, a high-fat diet reduces caloric intake of diabetics to normal, reflected by normal hypothalamic NPY and CRF content. How the brain senses these changes in diet is unknown. To date, no hormonal changes explain these diet-induced changes in caloric intake. We tested whether the common branch of the hepatic vagus mediates the fat signal. We presented fat in two ways. First, diabetic and vehicle-treated rats were offered a cup of lard in addition to their normal high-carbohydrate diet. Second, we switched diabetic rats from high-carbohydrate diet to high-fat diet, without choice. In streptozotocin-treated rats, both methods resulted in fat-induced inhibition of caloric intake and normalization of hypothalamic neuropeptides to nondiabetic levels. Strikingly, common branch hepatic vagotomy (unlike gastroduodenal vagotomy) entirely blocked these fat-induced changes. Although a shift in hepatic energy status did not explain the lard-induced changes in diabetic rats, the data suggested that common hepatic branch vagotomy does not interfere with hepatic energy status. Furthermore, common branch hepatic vagotomy without diabetes induced indexes of obesity. Abnormal function of the hepatic vagus, as occurs in diabetic neuropathy, may contribute to diabetic obesity.