（封面圖片：出生12天後小鼠的下丘腦共聚焦圖像，放大倍數4000。紅色螢光部分為弓狀核神經細胞軸突，它們支配室旁核活動。藍色部分為細胞核。）
下丘腦（hypothalamus）是負責接收、整合以及發出食慾調節信號，並且維持體重穩定的腦部中樞。一旦生物肌體對於食慾的調節發生紊亂，就可能產生肥胖。動物的神經系統通過產生促進或抑制食慾的內分泌因子，從而形成下丘腦神經投射環路，它們構成食慾調節網絡。其中，下丘腦的弓狀核（arcuate nucleus）是調節能量平衡的關鍵結構，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《細胞—代謝》（Cell Metabolism）上，來自美國和法國的一組科學家發現，在遺傳上更易發生肥胖的小鼠，其大腦的以上投射迴路也存在明顯的變化，這些變化會減少小鼠在出生後對於瘦素作用的反應。食物引起的肥胖（DIO）有多種遺傳模式，而DIO個體在飲食中加入適量脂肪後會產生一定的代謝症狀。
在研究中科學家們發現，通過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瘦素的抵抗症狀，而這些小鼠的下丘腦弓狀核投射存在缺陷，並且這類缺陷將一直持續到成年期。在DIO新生兒個體中，瘦素活體激發下丘腦弓狀核神經細胞內信號產生以及體外促進神經突起生長的能力被大大減弱。所以研究人員認為，對於那些易發生肥胖的動物而言，它們與能量平衡相關的下丘腦路徑存在異常，而這種異常或許是出生後生長過程中，下丘腦弓狀核神經細胞對瘦素反應力下降造成的。（科學網 何宏輝/編譯）
（《細胞—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
sbouret@chla.usc.edu
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.