LONG-TERM AND RAPID REGULATION OF OB MESSENGER-RNA LEVELS IN ADIPOSE-TISSUE FROM NORMAL (SPRAGUE-DAWLEY RATS) AND OBESE (DB DB MICE, FA/FA RATS) RODENTS/

Increased levels of mRNA transcribed from the ob gene in adipose tissu e of obese/hyperinsulinaemic Zucker (fa/fa) rats were detectable as ea rly as 3 weeks after birth and continued to rise there after in parall el with body weight and serum insulin. mRNA levels of two other fat-sp ecific genes (ARL4, FST44) were unaltered. In C57BL/KsJ db/db mice, ob mRNA levels also increased in parallel with body weight and serum ins ulin, and remained elevated in older animals when insulin levels decre ased. In heterozygous control animals (db/ +; fa/Fa), mRNA levels were comparable with those in the homozygous controls. In normal Sprague D awley rats, the ob mRNA increased continuously, but more slowly than i n Zucker rats, in parallel with body weight and insulin levels, and re ached 15 times higher levels in the heaviest rats (400 g) studied. In Sprague Dawley rats made diabetic by an injection of streptozotocin, o b mRNA levels were reduced by approximately 50 % after 24h. A 24-h fas ting 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 r educed in both groups. These data indicate that ob mRNA levels increas e in both normal and obese rodents in parallel with age, body weight a nd serum insulin, reflecting an early (Zucker rats, db-mice) or slowly developing (Sprague Dawley rats) resistance to leptin and insulin. Th is increase does not appear to be mediated by the recently described r apid regulation of ob mRNA by insulin, but seems to be due to a differ ent, long-term control mechanism which signals the size of the fat dep ots.