Effects of adrenalectomy before weaning in the genetically obese Zucker rat (fa/fa).

1. Lean (Fa/?) and obese (fa/fa) Zucker rats were adrenalectomized or sham-operated at 19 d of age (3 d before weaning). Injection of corticosterone for 3 d after weaning (1.0 mg/d) was necessary to ensure survival of adrenalectomized fa/fa but not Fa/? rats. Intact and adrenalectomized fa/fa rats had a lower rectal temperature than Fa/? animals before and 3 d after adrenalectomy. The post-weaning survival of adrenalectomized fa/fa rats was enhanced by maintenance at an ambient temperature of 30 degrees rather than 22 degrees. 2. Adrenalectomized and sham-operated rats were therefore kept at 30 degrees, fed ad-lib. and killed at 34 d. Adrenalectomy had only small effects on the growth, body composition and appetite of Fa/? rats. The hyperphagia, greater lipid content, reduced protein content and hyperinsulinaemia of fa/fa rats were completely abolished by adrenalectomy. 3. Intact fa/fa rats had higher liver glycogen contents and higher activities of the hepatic enzymes tyrosine aminotransferase (EC 2.6.1.5) and acetyl CoA carboxylase (EC 6.4.1.2) than intact Fa/? animals. Adrenalectomy abolished these phenotypic differences. 4. Injection of adrenalectomized rats with 1.0 mg corticosterone-21-acetate daily from weaning to 34 d restored the abnormal body composition, hyperphagia, hyperinsulinaemia, higher hepatic glycogen and enzyme activities of fa/fa rats. 5. In a second experiment adrenalectomized rats were injected with 1.0 mg corticosterone-21-acetate daily from weaning to 34 d and kept at 22 degrees. fa/fa rats adrenalectomized and injected with corticosterone had a reduced body lipid content compared with intact fa/fa rats but still contained more lipid than intact or similarly treated Fa/? animals. 6. In both experiments adrenalectomized Fa/? and fa/fa rats injected daily with corticosterone had the same plasma concentrations of this hormone when killed 3 h after the last injection at 34 d. It is concluded that corticosterone is required for expression of the abnormal appetite, hyperinsulinaemia and body composition of the fa/fa rat.