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. [...]