Energy sensing mechanism of the brain regulating feeding and reproduction

葡萄糖激酶（Glucokinase，GK）是一种在感知血糖水平中起关键作用的酶，它在脑的不同区域均有表达。本研究发现GK基因在第四脑室壁（4V）、下丘脑腹内侧核、下丘脑外侧核和中缝隐核等脑区的转录起始位点位于胰腺型启动子附近。在上述脑区中，在外周注射2-脱氧葡萄糖（一种葡萄糖抑制剂）后，4V区壁的GK主要B1亚型的转录减少，表明该脑区可能在转录水平上感受到葡萄糖可用性的减少。目前的研究表明，注射3-羟基丁酸酯（3 HB），一种酮体，到4V饥饿反应，如增加食物摄入， ...更多信息 正常大鼠促性腺激素释放减少。接下来，我们假设室管膜细胞衬里，4V感觉酮体，以及葡萄糖，调节生殖功能和摄食行为。为探讨糖尿病大鼠4V内单羧酸转运体介导的摄食量增加以及4V内室管膜细胞对3 HB的反应，将单羧酸转运体1（MCT 1）抑制剂对氯汞苯磺酸（pCMBS）注射到正常或链脲佐菌素（STZ）诱导的糖尿病大鼠4V内。此外，在离体条件下测定了正常大鼠4V室管膜细胞内游离钙浓度（[Ca^<2+>]i）对酮体的反应。结果表明，在糖尿病大鼠中，通过将pCMBS以剂量依赖性方式施用到4V中来减少增加的食物摄入。在体外实验中，3 HB可增加室管膜细胞[Ca^<2+>]i。免疫组化显示MCT 1定位于4V室管膜细胞。这些结果表明，食物摄入量增加是由循环中酮体增加引起的。后脑的室管膜细胞可能是介导食物摄入的病理或生理变化的酮体感受器。少

The present study aimed to understant the energy sensing mechanism in the brain to regulate feeding and reproduction.Glucokinase (GK), an enzyme playing a key role in sensing blood glucose levels, is expressed in the various brain areas. The present study revealed that the transcription start sites of GK gene in the brain areas, such as the wall of the fourth ventricle (4V), hypothalamic ventromedial nucleus, lateral hypothalamus, and raphe obsculus nuclei, were located near the pancreatic-type promoter. Of the above brain areas, the wall of the 4V sowed decreased transcription of the major B1 isoform of GK after the peripheral injection of 2-deoxyglucose, a glucose inhibitor, suggesting that the brain area may sense the decreased availability of glucose at the transcriptional level.Diabetic rats show increased food intake and severe ketosis. The present study revealed that injection of 3-hydroxybutylate (3HB), a ketone body, into the 4V hunger responses, such as increased food intake … More and decreased gonadotropin release in normal rats. Next, we hypothesized that the ependymocytes lining, the 4V sense ketone bodies, as well as glucose, to regulate reproductive functions and feeding behavior. To determine if the increased food intake is mediated by monocarboxylate transporter in the 4V in diabetic rats and if the ependymocytes lining 4V respond to 3HB in vitro, p-Chloromercuri benzese sulphonic acid (pCMBS), a monocarboxylate transporter 1 (MCT1) inhibitor, was injected into the 4V of normal or streptozotocin (STZ)-induced diabetic rats. In addition, in vitro responses of the intracellular calcium concentration ([Ca^<2+>]i) to ketone bodies was determined in dispersed ependymocytes taken from the 4V of normal rats. The results showed that increased food intake was reduced by the administration pCMBS into the 4V in a dose-dependent manner in the diabetic rats. In vitro [Ca^<2+>]i was increased by 3HB in the ependymocytes. Immunohistochemistry showed that MCT1 was located in the 4V ependymocytes. These results suggest that increased food intake is induced by the increased ketone bodies in the circulation. The ependymocytes in the hindbrain may be a ketone body sensor mediating pathological or physiological changes in the food intake. Less