Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice

Area of Science:

• Endocrinology
• Obesity Research
• Molecular Biology

Background:

• Adipsin expression is significantly reduced in various mouse models of obesity, including genetic (db/db, ob/ob) and chemically induced forms.
• The adipsin structural gene is located on chromosome 10, distinct from known mouse obesity genes.

Purpose of the Study:

• To investigate the role of the adrenal gland and glucocorticoids in the regulation of adipsin expression in obesity.
• To determine if glucocorticoids directly influence adipsin levels in vivo.

Main Methods:

• Adrenalectomy in ob/ob mice to assess adipsin protein and mRNA levels.
• Administration of corticosterone to both obese and lean mice to evaluate its effect on adipsin expression.
• Quantitative analysis of adipsin mRNA and protein levels.

Main Results:

• Adrenalectomy in ob/ob mice increased adipsin protein and mRNA, but not to lean control levels.
• Corticosterone administration blocked the effects of adrenalectomy and suppressed adipsin in lean mice.
• Glucocorticoids were shown to regulate adipsin expression in vivo, with a more severe suppression observed in obese mice.

Conclusions:

• The hyperglucocorticoid state in certain obese models significantly contributes to the lowering of adipsin mRNA and protein levels.
• Glucocorticoids play a key role in regulating adipsin expression.
• Additional unknown neuroendocrine factors may also suppress adipsin in obesity.