ORCHIECTOMY AND RESPONSE TO TESTOSTERONE IN THE DEVELOPMENT OF OBESITY IN YOUNG OTSUKA-LONG-EVANS-TOKUSHIMA FATTY (OLETF) RATS

OBJECTIVE: Withdrawal of testosterone prevents the development of hype rglycaemia in male Otsuha-Long-Evans-Tokushima Fatty (OLETF) rats, a m odel of non-insulin-dependent diabetes mellitus (NIDDM), but the exact mechanism has not been established. The present studies were undertak en to examine a possible role of testosterone in the development of ob esity in young OLETF rats who have not shown marked hyperphagia. METHO DS: Body weight, food intake and circulating concentrations of metabol ic factors including immunoreactive leptin (IRL) were measured at five weeks of age in young male OLETF rats and their lean controls, Long-E vans-Tokushima-Otsuka (LETO) rats. At six weeks of age, both LETO and OLETF rats were bilaterally orchiectomized (Orchx) and half of each gr oup implanted with a silastic tube containing testosterone. After a th ree week observation period, all animals were killed and circulating c oncentrations of metabolic factors and the ob gene expression in retro peritoneal white adipose tissues were measured. RESULTS: Body weight a nd 24 h food intake were already increased in OLETF rats at five weeks of age. Serum testosterone concentrations were significantly lower in OLETF rats than in LETO rats. Expression of the ob gene was significa ntly decreased in the retroperitoneal white adipose tissue of OLETF ra ts, and their serum IRL concentrations were lower. Food intake and bod y weight gain for three weeks after the operation were significantly l ower in the Orchx group of OLETF rats than in the sham-operated group. Hyperglycaemia, accompanied by hyperinsulinaemia, was attenuated by o rchiectomy in OLETF rats. Circulating IRL concentrations were signific antly higher in OLETF rats than in LETO rats and decreased by orchiect omy. Testosterone supplement reversed all of the changes caused by orc hiectomy in OLETF rats. In contrast, the changes, which were observed after orchiectomy in OLETF rats, were not obvious in LETO rats. CONCLU SION: The present data indicate that testosterone plays a role in the development of obesity and NIDDM in young OLETF rats, but that changes of leptin production in white adipose tissue may not be important in the development of obesity in young OLETF rats.