Effects of Mirabegron, a β‐Adrenergic Receptor Agonist, on Metabolic and Cardiovascular Parameters in Obese Mice
Authors: Zanesco Angelina , da silva Carmem P Valga , Calmasini Fabiano B , Alexandre Eduardo C , Candido Tuany , Monica Fabiola T , Delbin Maria A 
Published: November 2023

Background

Mirabegron, a selective β‐adrenergic receptor (β‐AR) agonist, has been approved for the treatment of overactive bladder. Given the pharmacological properties in activating β‐AR, studies of this compound on metabolism and adipose tissues could open new possibilities for obesity management.

Aims

The objective of this study was to examine the effect of Mirabegron on adipose tissue, metabolic parameters and cardiovascular system in obese mice.

Methods

C57BL/6J mice were divided into four groups: vehicle control group (CTR); control group treated with mirabegron (CTR‐Mira), obese fed with high‐fat diet (HFD) and obese fed with high‐fat diet treated with mirabegron (HFD‐Mira). High fat diet was given for 12 weeks. A 2‐week treatment of mirabegron (10 mg/kg) initiated at 11th‐week of the protocol design. The study lasted 12 weeks. Body weight, epididymal fat mass, energy intake, lipid profile, blood glucose, blood pressure and heart rate were evaluated. Concentration‐response curves to acetylcholine (ACh) and serotonin (5‐HT) were obtained in aorta with perivascular adipose tissue (PVAT+) or without (PVAT‐).

Results

A 2‐week treatment of mirabegron was effective in reducing epididymal fat in obese mice comparing with HFD group, approximately 25% (CTR: 0.2±01; CTR‐Mira: 0.1±0.01; HFD: 1.6±0.1; HFD‐Mira: 1.2±0.1 g) and body weight, approximately 9% % (CTR: 30.9 ± 0.5; CTR‐Mira: 29.8 ± 0.5; HFD: 41.8 ± 0.5; HFD‐Mira: 38.01 ± 0.2 g) even though energy intake was not affected by mirabegron in HFD‐Mira group. Atherogenic index based on lipid profile was reduced in HFD‐Mira group comparing with HFD group, approximately 122% (CTR: 0.33±0.02; CTR‐Mira: 0.31±0.04; HFD: 0.8±0.1; HFD‐Mira: 0.36±0.08). Mirabegron treatment failed to revert the increased blood glucose in HFD group. In addition, blood pressure and heart rate were not affected by any treatment (diet or mirabegron). As expected, HFD provokes an impairment of endothelium‐dependent relaxing responses in aorta with PVAT, at pEC50 level (CTR: 7.2±0.08; CTR‐Mira: 7.1±0.08; HFD: 6.7±0.1; HFD‐Mira: 6.4±0.3) that was not modified by mirabegron. In contrast, mirabegron increased the maximal responses to 5‐HT in aorta from HFD‐Mira group with PVAT (CTR: 69±8; CTR‐Mira: 77±11; HFD: 66±9; HFD‐Mira: 109±10 %). We found no alterations in the concentration‐responses curves to both agonists in aorta without PVAT in all groups.

Conclusions

A 2‐week treatment of mirabegron was effective in reducing the body weight and epididymal adipose tissue in obese mice without interfering with blood pressure, heart rate and endothelium‐dependent relaxing responses to ACh. In addition, atherogenic index was also improved in obese mice treated with β‐AR agonist. Therefore, mirabegron would be an interesting compound to be examined in the management of obesity in clinical trial.

Support or Funding Information

Sao Paulo Research Foundation and CAPES