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

Abstract

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° rather than 22°.2. Adrenalectomized and sham-operated rats were therefore kept at 30°, 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 fu/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°, fa/fu 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.