Himms-Hagen J
Int J Obes. 1985;9 Suppl 2:17-24.
Defective BAT thermogenesis is associated with obesity in all the different types of obese animal so far studied. The deficit in normal energy expenditure may be presumed to contribute to the high metabolic efficiency and, together with the hyperphagia, to the obesity of these animals. In two types of obese animal (the ob/ob mouse, the db/db mouse) an increased propensity to become torpid provides an additional energy conserving mechanism that contributes to the high metabolic efficiency. In all these animals an abnormality of hypothalamic function appears likely. Obviously animals with induced hypothalamic lesions (the VMH-lesioned rat, the GTG-obese mouse) have an interruption in the normal pathway that links diet and the sympathetic innervation of BAT. The fa/fa rat resembles these animals in failing to activate BAT thermogenesis in response to diet: the lesion may lie in the hypothalamus itself or elsewhere in the food-intestine-hypothalamus-BAT axis, for example in intestinal peptide hormones. The ob/ob mouse has a peculiar hypothalamic defect that interferes with control of thermogenesis in BAT as well as impairing or exaggerating some aspects of thermoregulation. The db/db mouse resembles the ob/ob mouse but, since the defect is genetically distinct, presumably has a different lesion at the molecular level.
在迄今所研究的所有不同类型的肥胖动物中，褐色脂肪组织（BAT）产热缺陷均与肥胖有关。正常能量消耗的不足可能被认为导致了高代谢效率，并且与食欲亢进一起，导致了这些动物的肥胖。在两种肥胖动物（ob/ob小鼠、db/db小鼠）中，变得蛰伏的倾向增加提供了一种额外的能量保存机制，这有助于提高代谢效率。在所有这些动物中，下丘脑功能异常似乎是可能的。显然，患有诱发性下丘脑损伤的动物（VMH损伤大鼠、GTG肥胖小鼠）在连接饮食与BAT交感神经支配的正常途径上存在中断。fa/fa大鼠在对饮食做出反应时未能激活BAT产热，这一点与这些动物相似：病变可能位于下丘脑本身或食物-肠道-下丘脑-BAT轴的其他部位，例如肠道肽激素。ob/ob小鼠有一个特殊的下丘脑缺陷，它既干扰BAT产热的控制，又损害或夸大体温调节的某些方面。db/db小鼠与ob/ob小鼠相似，但由于缺陷在基因上是不同的，推测在分子水平上有不同的病变。
