The effects of adrenalectomy and aldosterone replacement in transgenic mice expressing antisense RNA to the type 2 glucocorticoid receptor
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Published on: September 26, 2018
T W Castonguay1, S Beaulieu, R L Eskay
1Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA. tc27@umail.umd.edu
Abstract:
Bilateral adrenalectomy (ADX) either prevents or attenuates obesity in several animal models. Mice that express an antisense RNA to the glucocorticoid receptor (GCR) are obese. The present study was conducted to examine the effects of ADX and aldosterone (ALDO) replacement on the rate of weight gain and body composition of mice bearing an antisense GCR gene construct. Twenty-eight male transgenic mice bearing the antisense GCR construct and 16 male B6C/3F1 mice were either bilaterally ADX or given sham operations. At the time of surgery, some of the ADX mice and all of the sham-operated mice were implanted with 100-mg cholesterol (CHOL) pellets inserted subcutaneously in the subscapular region. The remaining ADX mice were implanted with 100-mg 1% w/w ALDO pellets using CHOL as vehicle. All mice were returned to their home cages for 2 weeks. They were then decapitated and the blood was collected for corticosterone, ALDO, insulin, and leptin radioimmunoassay. Carcasses were eviscerated and prepared for gravimetric analyses, including bomb calorimetry. ADX resulted in a significant drop in carcass fat in both transgenic and wildtype groups. ALDO prevented the decrease in carcass fat in both groups. Two weeks after ADX, transgenic mice were as fat as sham-operated wildtype controls, whereas both sham-operated and ALDO-treated transgenic groups were significantly fatter. Despite observing a reliable decrease in carcass fat following ADX, no corresponding decrease in circulating leptin was found.
Insights
Bilateral adrenalectomy (ADX) reduces body fat in mice. Aldosterone (ALDO) replacement prevents this fat loss, indicating its role in regulating body composition in mice with altered glucocorticoid receptor (GCR) function.
Area of Science:
- Endocrinology
- Metabolic research
- Genetics
Background:
- Bilateral adrenalectomy (ADX) is known to prevent or reduce obesity in animal models.
- Mice engineered to express antisense RNA against the glucocorticoid receptor (GCR) exhibit obesity.
- The interplay between adrenal hormones and GCR function in obesity regulation requires further investigation.
Purpose of the Study:
- To investigate the impact of ADX and subsequent aldosterone (ALDO) replacement on weight gain and body composition.
- To examine these effects in transgenic mice with a GCR antisense gene construct.
Main Methods:
- Surgical procedures included bilateral adrenalectomy (ADX) or sham operations in transgenic and wildtype mice.
- Hormone replacement was achieved using subcutaneous cholesterol (CHOL) or aldosterone (ALDO) pellets.
- Body composition was assessed via gravimetric analysis and bomb calorimetry; blood was analyzed for hormone levels (corticosterone, ALDO, insulin, leptin).
Main Results:
- ADX significantly decreased carcass fat in both transgenic and wildtype mice.
- Aldosterone (ALDO) administration prevented the reduction in carcass fat observed after ADX.
- Transgenic mice treated with ALDO or sham-operated transgenic mice were significantly fatter than sham-operated wildtype controls.
Conclusions:
- Adrenalectomy leads to a reduction in body fat, which is reversed by aldosterone replacement.
- Aldosterone plays a crucial role in maintaining body fat, particularly in the context of altered glucocorticoid receptor signaling.
- Despite changes in body fat, adrenalectomy did not alter circulating leptin levels in these models.
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