Sims J S, Lorden J F
Behav Brain Res. 1986 Dec;22(3):265-81. doi: 10.1016/0166-4328(86)90071-9.
Lesions of the paraventricular nucleus of the hypothalamus (PVN) produce obesity and hyperphagia. However, the underlying mechanism is unknown. The connections of the PVN with brainstem centers for autonomic control suggest that a change in autonomic function could mediate the PVN obesity syndrome. We examined this hypothesis in a series of 3 experiments, searching specifically for changes in insulin secretion. Rats with PVN lesions were hyperphagic and hyperinsulinemic, when obese. However, hyperinsulinemia could not be detected prior to the onset of obesity or following weight reduction. Subdiaphragmatic vagotomy reversed the PVN obesity and lowered insulin levels below those of sham-vagotomized rats. Since noradrenergic innervation of the hypothalamus is implicated in feeding, hypothalamic norepinephrine (NE) was depleted by injection of 6-hydroxydopamine into the central tegmental tract, posterior to the hypothalamus. The effects of NE depletion was compared with those of PVN lesions. Loss of hypothalamic NE resulted in hyperphagia with no increase in body weight and no change in insulin. Histological analyses indicated that the posterior PVN was the most effective lesion focus for producing disturbances in body weight and food intake. Although the results of these experiments implicate the autonomic nervous system in PVN obesity, basal hyperinsulinemia does not appear to be a primary feature of the syndrome.
下丘脑室旁核（PVN）损伤会导致肥胖和食欲亢进。然而，其潜在机制尚不清楚。PVN与自主神经控制的脑干中枢之间的联系表明，自主神经功能的改变可能介导了PVN肥胖综合征。我们在一系列3个实验中检验了这一假设，特别寻找胰岛素分泌的变化。PVN损伤的大鼠在肥胖时食欲亢进且胰岛素水平升高。然而，在肥胖开始之前或体重减轻之后均未检测到高胰岛素血症。膈下迷走神经切断术可逆转PVN肥胖，并使胰岛素水平降至假手术迷走神经切断术大鼠以下。由于下丘脑的去甲肾上腺素能神经支配与进食有关，通过向位于下丘脑后方的中央被盖束注射6-羟基多巴胺来耗尽下丘脑去甲肾上腺素（NE）。将NE耗尽的影响与PVN损伤的影响进行比较。下丘脑NE的缺失导致食欲亢进，但体重没有增加，胰岛素也没有变化。组织学分析表明，PVN后部是导致体重和食物摄入量紊乱的最有效损伤部位。尽管这些实验结果表明自主神经系统与PVN肥胖有关，但基础高胰岛素血症似乎并不是该综合征的主要特征。
