The role of corticosterone in the defective control of brown adipose tissue thermogenesis in mice with gold thioglucose-induced obesity.

Abstract

Gold thioglucose (GTG) leads to hypothalamic obesity in mice. The purpose of this study was to determine if hypersensitivity to corticosterone is present in mice with hypothalamic obesity. Mice were injected with either saline or GTG and sham-adrenalectomized or adrenalectomized (adx). The adx animals received cholesterol implants containing corticosterone. Certain abnormalities of GTG-mice, namely hyperphagia, increased white adipose tissue and brown adipose tissue (BAT) weights and hyperinsulinemia are normalized by adrenalectomy and returned in virtually full force at low levels of corticosterone. Other abnormalities like high body weight and reduced BAT mitochondrial GDP binding are not affected. BAT protein was not affected by adrenalectomy in either lean or obese animals and was reduced by corticosterone replacement in both. It is concluded that GTG-mice are hypersensitive to an action of corticosterone which plays an important role in the development of their obesity. However, some abnormalities, like the suppressed BAT thermogenesis, persist in the adx state and seem to be due to metabolic defects primarily caused by the GTG lesions that are not dependent on corticosterone. (Abstract shortened by UMI.)