（封面圖片：出生12天后小鼠的下丘腦共聚焦圖像，放大倍數(shù)4000,。紅色熒光部分為弓狀核神經(jīng)細(xì)胞軸突，它們支配室旁核活動(dòng)。藍(lán)色部分為細(xì)胞核,。）
下丘腦（hypothalamus）是負(fù)責(zé)接收、整合以及發(fā)出食欲調(diào)節(jié)信號(hào),，并且維持體重穩(wěn)定的腦部中樞,。一旦生物肌體對(duì)于食欲的調(diào)節(jié)發(fā)生紊亂，就可能產(chǎn)生肥胖,。動(dòng)物的神經(jīng)系統(tǒng)通過(guò)產(chǎn)生促進(jìn)或抑制食欲的內(nèi)分泌因子,，從而形成下丘腦神經(jīng)投射環(huán)路,，它們構(gòu)成食欲調(diào)節(jié)網(wǎng)絡(luò)。其中,，下丘腦的弓狀核（arcuate nucleus）是調(diào)節(jié)能量平衡的關(guān)鍵結(jié)構(gòu),，而瘦素（leptin）是下丘腦投射正常形成所必需的因素。
在2008年2月6日出版的《細(xì)胞—代謝》（Cell Metabolism）上,，來(lái)自美國(guó)和法國(guó)的一組科學(xué)家發(fā)現(xiàn),，在遺傳上更易發(fā)生肥胖的小鼠，其大腦的以上投射回路也存在明顯的變化,，這些變化會(huì)減少小鼠在出生后對(duì)于瘦素作用的反應(yīng),。食物引起的肥胖（DIO）有多種遺傳模式，而DIO個(gè)體在飲食中加入適量脂肪后會(huì)產(chǎn)生一定的代謝癥狀,。
在研究中科學(xué)家們發(fā)現(xiàn),，通過(guò)飲食引起肥胖的小鼠中有一部分在變得肥胖之前就存在對(duì)瘦素的抵抗癥狀，而這些小鼠的下丘腦弓狀核投射存在缺陷,，并且這類(lèi)缺陷將一直持續(xù)到成年期,。在DIO新生兒個(gè)體中，瘦素活體激發(fā)下丘腦弓狀核神經(jīng)細(xì)胞內(nèi)信號(hào)產(chǎn)生以及體外促進(jìn)神經(jīng)突起生長(zhǎng)的能力被大大減弱,。所以研究人員認(rèn)為,，對(duì)于那些易發(fā)生肥胖的動(dòng)物而言，它們與能量平衡相關(guān)的下丘腦路徑存在異常,，而這種異?；蛟S是出生后生長(zhǎng)過(guò)程中，下丘腦弓狀核神經(jīng)細(xì)胞對(duì)瘦素反應(yīng)力下降造成的,。（科學(xué)網(wǎng) 何宏輝/編譯）
（《細(xì)胞—代謝》（Cell Metabolism）,，Vol 7, 179-185, 06 February 2008，Sebastien G. Bouret, Richard B. Simerly）
生物谷推薦原始出處：
Cell Metabolism, Vol 7, 179-185, 06 February 2008
Short Article
Hypothalamic Neural Projections Are Permanently Disrupted in Diet-Induced Obese Rats
Sebastien G. Bouret,1,2, Judith N. Gorski,3,4,5 Christa M. Patterson,3,4 Stephen Chen,1 Barry E. Levin,3,4 and Richard B. Simerly1
1 Neuroscience Program, The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA
2 Inserm, U837, Jean-Pierre Aubert Research Center, Université Lille 2, 59045 Lille, France
3 Neurology Service, Veterans Affairs Medical Center, East Orange, NJ 07018, USA
4 Department of Neurology and Neurosciences, New Jersey Medical School, Newark, NJ 07103, USA
5 Department of Pharmacology, Merck Research Laboratories, Rahway, NJ 07065, USA
Corresponding author
Sebastien G. Bouret
[email protected]
The arcuate nucleus of the hypothalamus (ARH) is a key component of hypothalamic pathways regulating energy balance, and leptin is required for normal development of ARH projections. Diet-induced obesity (DIO) has a polygenic mode of inheritance, and DIO individuals develop the metabolic syndrome when a moderate amount of fat is added to the diet. Here we demonstrate that rats selectively bred to develop DIO, which are known to be leptin resistant before they become obese, have defective ARH projections that persist into adulthood. Furthermore, the ability of leptin to activate intracellular signaling in ARH neurons in vivo and to promote ARH neurite outgrowth in vitro is significantly reduced in DIO neonates. Thus, animals that are genetically predisposed toward obesity display an abnormal organization of hypothalamic pathways involved in energy homeostasis that may be the result of diminished responsiveness of ARH neurons to the trophic actions of leptin during postnatal development.
