Cusin I, Sainsbury A, Doyle P, Rohner-Jeanrenaud F, Jeanrenaud B
Laboratories de Recherches Métaboliques, Faculty of Medicine, Geneva University, Switzerland.
Diabetes. 1995 Dec;44(12):1467-70. doi: 10.2337/diab.44.12.1467.
Obesity and non-insulin-dependent diabetes are estimated to affect millions of people in the world. This pathology is multifactorial, comprising complex interactions of genetic and environmental factors and lacking a specific therapy. Great interest arose from the recent discovery of the ob gene expressed only in adipose tissue and coding for a protein that appears to regulate adiposity, potentially by acting as a satiety factor. We report here that in normal rats, ob mRNA is respectively up- or downregulated by a rise in insulinemia (induced by 2-day insulin infusion while maintaining euglycemia) or a decrease in insulinemia (induced by a 3-day fast). Our results also show that in genetically obese fa/fa rats studied longitudinally, white adipose tissue ob mRNA levels increase in parallel with early occurring and steadily increasing hyperinsulinemia. This results in adult obese animals having markedly higher ob mRNA levels than age-matched normoinsulinemic lean rats. Furthermore, in adult obese rats, ob mRNA escapes down-regulation as normalization of hyperinsulinemia due to fasting fails to reduce the high ob mRNA levels.
据估计，肥胖症和非胰岛素依赖型糖尿病影响着全球数百万人。这种病理状况是多因素的，包括遗传和环境因素的复杂相互作用，并且缺乏特定的治疗方法。最近发现仅在脂肪组织中表达的ob基因编码一种蛋白质，该蛋白质似乎通过作为饱腹感因子来调节肥胖，这引起了人们极大的兴趣。我们在此报告，在正常大鼠中，胰岛素血症升高（通过维持血糖正常的2天胰岛素输注诱导）或胰岛素血症降低（通过3天禁食诱导）分别上调或下调ob mRNA。我们的结果还表明，在纵向研究的遗传性肥胖fa/fa大鼠中，白色脂肪组织ob mRNA水平与早期出现且持续增加的高胰岛素血症平行升高。这导致成年肥胖动物的ob mRNA水平明显高于年龄匹配的正常胰岛素水平的瘦大鼠。此外，在成年肥胖大鼠中，由于禁食导致高胰岛素血症正常化未能降低高ob mRNA水平，ob mRNA逃避了下调。
