ß3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on ß3-adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, ß3-receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased ß3-receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in ß3-adrenergic receptor gene expression in the brain. Greater reduction of ß3-adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of ß3-adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

Adipogenesis and aldosterone: a study in lean tryptophan-depleted rats.

Next to epithelial tissues, mineralocorticoid receptors are also expressed in adipose tissue and are involved in the process of adipogenesis. Mineralocorticoid receptors in adipose tissue are likely to be activated mainly by glucocorticoids. The aim of the present study was to test the hypothesis that the processes related to adipogenesis are modified under the conditions associated with high circulating aldosterone. We have made advantage of a model of depression based on tryptophan depletion in which we have previously demonstrated that the elevation of serum aldosterone precedes that of corticosterone. Sixty adult female Sprague-Dawley rats were fed either a low tryptophan diet or control diet for 4 (elevation of aldosterone only), 7 and 14 days (broader neuroendocrine activation) respectively. Gene expression of several adipogenic factors, CD31, interleukin-6, adiponectin, resistin and leptin were evaluated. Levels of mRNAs coding for adipogenic, angiogenic and inflammatory factors in adipose tissue were elevated at 4 and 7 days of tryptophan depletion. Additionally, gene expression of aldosterone sensing 11-ß-hydroxysteroid dehydrogenase 2 and mineralocorticoid receptors were elevated. All changes disappeared at 14 days of tryptophan depletion. Synchronously an increase of adipose tissue mass was observed. Although direct evidence is not provided, observed changes in gene expression may be related to the action of aldosterone on mineralocorticoid receptors. Our findings represent the first data on any changes in gene expression in adipose tissue in animal models of depression.