Effects of adrenalectomy and hormone replacement on B6C3F1 mice fed a high-fat diet

Bilateral adrenalectomy (ADX) causes decreased circulating leptin in both obese and lean mice. It remains unclear whether the decreased plasma leptin after ADX is due to decreased adipose tissue or is due to decreased circulating glucocorticoids. The present experiment was performed to test the hypothesis that the absence of glucocorticoids from circulation is sufficient to decrease circulating leptin. Sixty-four adult male B6C3F1 mice were individually housed and fed either Purina rat chow or an experimental diet. After 6 weeks, mice fed the experimental diet gained more weight than mice fed the control diet. Each dietary group was then subdivided into four groups: ADX with cholesterol replacement (ADX-CHOL), ADX with corticosterone (CORT) replacement (ADX+CORT), ADX with aldosterone (ALDO) replacement (ADX+ALDO), and sham operation (SHAM). Two days after surgery, mice were killed and exsanguinated and the carcasses were prepared for gravimetric analyses. Blood was collected and centrifuged and the plasma was assayed for leptin, CORT, and ALDO. Blood glucose was determined using whole blood taken before centrifugation. There was no difference in body weight due to ADX after 2 days. Mice fed the experimental diet had higher circulating leptin than those fed the control diet. The ADX+CORT groups (both experimental and control diets) had higher plasma leptin concentrations than the other groups. No differences were observed between ADX-CHOL and SHAM groups. These results suggest that circulating leptin is not directly controlled by glucocorticoids. The effect of ADX on circulating leptin reported by others may be the consequence of decreased adiposity.