Faculty Arizona State University Phoenix, Arizona, United States
Objectives: Mirabegron, a beta-3 adrenergic receptor agonist, is a browning agent, but no study has delivered it directly to subcutaneous white adipose tissue (WAT) to induce its browning. The study objective was to directly inject mirabegron into the inguinal WAT (iWAT) of overweight and obese mice and determine the browning and anti-obesity effects.
Methods: Male C57BL/6J mice were fed with HFD (45% kcal from fat) for 5 weeks and 12 weeks to induce overweight and obesity, respectively. The saline control and mirabegron were directly injected biweekly into iWAT at 15 mg/kg body weight/injection for 5 weeks in both overweight and obese mice. Mouse body composition was measured by Echo MRI. The mRNA expression levels of genes associated with iWAT browning were quantified via real time-PCR. IWAT samples were sectioned and stained with H & E, and adipocyte size was measured using Image J software. Serum chemistry profile was measured by an Heska Dri-Chem Blood Chemistry Analyzer.
Results: Mirabegron decreased body weight by 12.4% and 7.0 %, body fat percentage by 17.4 % and 16.8 %, iWAT mass by 26.1% and 24.6 % that were associated with 5.2-fold and 3.1-fold increase of iWAT UCP1 expression in overweight and obese mice, respectively. Similarly, the gene expression of TMEM26 showed the same trends in these mice. As compared to control overweight and obese mice, the mirabegron-treated mice had significantly 2.2-fold and 1.9-fold smaller adipocyte sizes in iWAT, respectively. Mirabegron did not change food intake and lean mass. Serum chemistry analysis revealed no significant differences in renal function, liver function, or electrolyte levels between the control and mirabegron groups in both overweight and obese mice.
Conclusions: Direct administration of mirabegron into subcutaneous WAT can induce its browning, and result in body weight and fat loss without decreasing lean mass, suggesting its potential use as an effective and safe anti-obesity treatment.
