（封面图片：出生12天后小鼠的下丘脑共聚焦图像，放大倍数4000。红色荧光部分为弓状核神经细胞轴突，它们支配室旁核活动。蓝色部分为细胞核。）
下丘脑（hypothalamus）是负责接收、整合以及发出食欲调节信号，并且维持体重稳定的脑部中枢。一旦生物肌体对于食欲的调节发生紊乱，就可能产生肥胖。动物的神经系统通过产生促进或抑制食欲的内分泌因子，从而形成下丘脑神经投射环路，它们构成食欲调节网络。其中，下丘脑的弓状核（arcuate nucleus）是调节能量平衡的关键结构，而瘦素（leptin）是下丘脑投射正常形成所必需的因素。
在2008年2月6日出版的《细胞—代谢》（Cell Metabolism）上，来自美国和法国的一组科学家发现，在遗传上更易发生肥胖的小鼠，其大脑的以上投射回路也存在明显的变化，这些变化会减少小鼠在出生后对于瘦素作用的反应。食物引起的肥胖（DIO）有多种遗传模式，而DIO个体在饮食中加入适量脂肪后会产生一定的代谢症状。
在研究中科学家们发现，通过饮食引起肥胖的小鼠中有一部分在变得肥胖之前就存在对瘦素的抵抗症状，而这些小鼠的下丘脑弓状核投射存在缺陷，并且这类缺陷将一直持续到成年期。在DIO新生儿个体中，瘦素活体激发下丘脑弓状核神经细胞内信号产生以及体外促进神经突起生长的能力被大大减弱。所以研究人员认为，对于那些易发生肥胖的动物而言，它们与能量平衡相关的下丘脑路径存在异常，而这种异常或许是出生后生长过程中，下丘脑弓状核神经细胞对瘦素反应力下降造成的。（科学网 何宏辉/编译）
（《细胞—代谢》（Cell Metabolism），Vol 7, 179-185, 06 February 2008，Sebastien G. Bouret, Richard B. Simerly）
生物谷推荐原始出处：
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.
