OVEREXPRESSION OF THE OBESE (OB) GENE IN ADIPOSE-TISSUE OF HUMAN OBESE SUBJECTS
OVEREXPRESSION OF THE OBESE (OB) GENE IN ADIPOSE-TISSUE OF HUMAN OBESE SUBJECTS
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DOI：
10.1038/nm0995-950
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发表时间：
1995-09-01
期刊：
影响因子：
82.9
通讯作者：
SCHALLING, M
中科院分区：
文献类型：
--
作者：
LONNQVIST, F;ARNER, P;SCHALLING, M
肥胖伴随着并发症，如高血压，非胰岛素依赖型糖尿病和动脉粥样硬化，这反过来又会导致缺血性心脏病，中风和过早死亡（1-3）。能量摄入和能量消耗失衡导致肥胖的潜在机制仍然存在争议。在大多数人群中，肥胖症在女性中比男性更常见，并且是一种多因素表型，可能由遗传和非遗传因素的复杂网络引起。遗传因素对肥胖的相对重要性正在讨论中（4-7）。在具有导致极度肥胖的表型的近交系小鼠中使用多态性标记进行基因组搜索（8，9），并且正在进行人类候选基因的研究，以试图鉴定导致肥胖的基因。有证据表明，体重是生理调节的（4，10，11），并且已经假设脂肪的储存可能向大脑提供身体肥胖的信号，这反过来可能使受试者吃得更少，燃烧更多的燃料（12，13）。其中一种可能参与这种信号传导的分子是肥胖（ob）基因产物。ob突变导致小鼠严重肥胖和II型糖尿病（14，15）。小鼠ob基因及其人类同源物已被克隆和测序（8）。该基因在脂肪组织中表达，产物具有分泌蛋白的特征。我们使用原位杂交组织化学研究了从非肥胖和严重肥胖受试者获得的皮下和网膜脂肪组织中的人ob表达，并报告了肥胖人群中的过度表达。
Obesity is accompanied by complications such as hypertension, non-insulin-dependent diabetes mellitus and atherosclerosis, which in turn cause ischaemic heart disease, stroke and premature death(1-3). The underlying mechanisms behind imbalance in energy intake and energy expenditure that lead to obesity are still controversial. In most populations, obesity is more common among women than men and is a multifactorial phenotype, which may result from a complex network of genetic and nongenetic factors. The relative importance of genetic factors for obesity is under debate(4-7). Genome searches using polymorphic markers in inbred mice with phenotypes that result in extreme obesity(8,9) and studies of human candidate genes are being performed in an attempt to identify genes that contribute to obesity. There is evidence that body weight is physiologically regulated(4,10,11) and it has been postulated that the storage of fat may provide signals to the brain that the body is obese, which in turn may make the subject eat less and burn more fuel(12,13). One of the molecules that may be involved in such signalling is the obese (ob) gene product. Mutations in ob result in profound obesity and type II diabetes in mice(14,15). The mouse ob gene and its human homologue have been cloned and sequenced(8). The gene is expressed in adipose tissue and the product has features of a secreted protein, We have investigated human ob expression in subcutaneous and omental adipose tissue obtained from non-obese and massively obese subjects using in situ hybridization histochemistry and report on overexpression in obese people.