Igel M, Kainulainen H, Brauers A, Becker W, Herberg L, Joost H G
Institute of Pharmacology and Toxicology, RWTH Aachen, Germany.
Diabetologia. 1996 Jul;39(7):758-65. doi: 10.1007/s001250050508.
Increased levels of mRNA transcribed from the ob gene in adipose tissue of obese/hyperinsulinaemic Zucker (fa/fa) rats were detectable as early as 3 weeks after birth and continued to rise there after in parallel with body weight and serum insulin. mRNA levels of two other fat-specific genes (ARL4, FST44) were unaltered. In C57BL/KsJ db/db mice, ob mRNA levels also increased in parallel with body weight and serum insulin, and remained elevated in older animals when insulin levels decreased. In heterozygous control animals (db/+; fa/Fa), mRNA levels were comparable with those in the homozygous controls. In normal Sprague Dawley rats, the ob mRNA increased continuously, but more slowly than in Zucker rats, in parallel with body weight and insulin levels, and reached 15 times higher levels in the heaviest rats (400 g) studied. In Sprague Dawley rats made diabetic by an injection of streptozotocin, ob mRNA levels were reduced by approximately 50% after 24 h. A 24-h fasting period reduced the ob mRNA by 50% in lean Sprague Dawley and Fa/Fa, but not in obese Zucker fa/fa rats, although insulin levels were reduced in both groups. These data indicate that ob mRNA levels increase in both normal and obese rodents in parallel with age, body weight and serum insulin, reflecting an early (Zucker rats, db-mice) or slowly developing (Sprague Dawley rats) resistance to leptin and insulin. This increase does not appear to be mediated by the recently described rapid regulation of ob mRNA by insulin, but seems to be due to a different, long-term control mechanism which signals the size of the fat depots.
早在出生后3周，就可检测到肥胖/高胰岛素血症的Zucker（fa/fa）大鼠脂肪组织中ob基因转录的mRNA水平升高，此后其随着体重和血清胰岛素水平持续上升。另外两个脂肪特异性基因（ARL4、FST44）的mRNA水平未发生改变。在C57BL/KsJ db/db小鼠中，ob mRNA水平也随着体重和血清胰岛素水平平行升高，并且在老年动物中，当胰岛素水平下降时仍保持升高。在杂合对照动物（db/+；fa/Fa）中，mRNA水平与纯合对照动物相当。在正常的Sprague Dawley大鼠中，ob mRNA持续升高，但比Zucker大鼠升高得慢，与体重和胰岛素水平平行，在研究的最重的大鼠（400 g）中达到了高15倍的水平。在注射链脲佐菌素诱导糖尿病的Sprague Dawley大鼠中，24小时后ob mRNA水平降低了约50%。24小时禁食使瘦的Sprague Dawley大鼠和Fa/Fa大鼠的ob mRNA降低了50%，但肥胖的Zucker fa/fa大鼠没有降低，尽管两组的胰岛素水平都降低了。这些数据表明，在正常和肥胖的啮齿动物中，ob mRNA水平均随着年龄、体重和血清胰岛素水平平行升高，反映出对瘦素和胰岛素的早期（Zucker大鼠、db小鼠）或缓慢发展（Sprague Dawley大鼠）的抵抗。这种升高似乎不是由最近描述的胰岛素对ob mRNA的快速调节介导的，而是似乎归因于一种不同的长期控制机制，该机制发出脂肪储存大小的信号。
