Adipose tissue remodeling in response to corticosterone and β3-adrenergic receptor agonist mirabegron

Abstract

With the rise of metabolic diseases including obesity and type 2 diabetes, the need to investigate one of the most dynamic endocrine organs is critical for combating these diseases. Adipose tissue (AT) exists predominantly in two forms: white AT (WAT) and brown AT (BAT). This study set out to investigate how chronic levels of glucocorticoids (GC), namely corticosterone, influence AT, and if the negative effects of GCs can be combated with a β3-adrenergic receptor (β3AR) agonist, mirabegron. Mice were subjected to oral treatments of either, corticosterone (500µg/day), mirabegron (either 0.024mg/day or 0.24mg/day), a combination of the two, or naïve or vehicle (<1% ethanol) controls for four weeks. The corticosterone dose was chosen to match the level of corticosterone circulating in Cushing’s syndrome patients, and the mirabegron treatments were chosen to be a much lower dose (0.024mg/day) than or to closely resemble the maximal dosage approved (0.24mg/day) for overactive bladder patients. We hypothesized that mirabegron would offset the negative impacts of corticosterone-induced metabolic dysfunction and lipid accumulation within the AT depots. Corticosterone treatment resulted in BAT whitening, significantly (p≤0.05) increased body and AT weights, whole-body insulin resistance and circulating leptin levels. [...]