Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.
Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.
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DOI：
10.1073/pnas.93.8.3434
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发表时间：
1996-04
影响因子：
11.1
通讯作者：
T. M. Mizuno;H. Bergen;Toshiya Funabashi;S. Kleopoulos;Y. Zhong;W. Bauman;C. Mobbs
中科院分区：
文献类型：
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作者：
T. M. Mizuno;H. Bergen;Toshiya Funabashi;S. Kleopoulos;Y. Zhong;W. Bauman;C. Mobbs
肥胖（ob）基因突变会导致肥胖。该基因最近已被克隆，但调节其表达的因素尚未阐明。为了解决 ob 基因在体重和营养因素方面的调节问题，使用 Northern blot 分析来评估不同营养条件下小鼠（瘦、因饮食导致肥胖或遗传性（黄色刺豚鼠）肥胖）脂肪组织中的 ob mRNA。与瘦对照相比，两种肥胖形式的 ob mRNA 均升高，与血浆胰岛素和体重升高相关，但与血浆葡萄糖升高无关。在瘦 C57BL/6J 小鼠中，ob mRNA 在禁食 48 小时后下降，但在饮食引起的肥胖小鼠中则不然。同样，在瘦 C57BL/6J 对照中，但在肥胖的黄色小鼠中则不然，腹膜内注射。葡萄糖注射液显着增加ob mRNA。注射葡萄糖后长达 30 分钟，瘦小鼠的 ob mRNA 与血浆葡萄糖显着相关，但与血浆胰岛素无关。在一项仅针对瘦小鼠的单独研究中，ob mRNA 因禁食而被抑制 >90%，并且在腹腔注射后 30 分钟升高约 2 倍。注射葡萄糖或胰岛素。这些结果表明，在瘦动物中，葡萄糖和胰岛素增强 ob 基因表达。与我们在瘦小鼠中的结果相反，在肥胖动物中，ob mRNA 升高并且对营养状态相对不敏感，这可能是由于长期暴露于升高的血浆胰岛素和/或葡萄糖所致。
Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose.