Activation of Brown Adipose Tissue Metabolism Using Mirabegron

Summary

Could sympathomimetics and sympatholytics drugs safe for the management of Type 2 Diabetes (T2D)? Based on recent evidence, we propose that pharmacological stimulation of Beta-3 adrenergic receptor (ADBR3) at higher doses of Mirabegron may be required to elicit changes in glycemia, but should be combined with Beta-1 adrenergic receptor (ADRB1) antagonists to suppress the unwanted effects on the cardiovascular system. Together, several results establish a previously unappreciated cross-talk between Gs-coupled ADRB1 and ADRB3 in adipose tissue for the control of glucose homeostasis. Moreover, these data suggest that antagonizing ADRB1 may be a good way to significantly lower the dose of ADRB3 agonist required for glucose control. Therefore, we believe that there are therapeutic opportunities in targeting adrenergic receptors for the treatment of T2D at least in young/middle aged people.

Timeline

Start

2021-01-21

Primary completion

2022-04-04

Completion

2022-04-04

Publications

• Results Dumont L, Caron A, Richard G, Croteau E, Fortin M, Frisch F, Phoenix S, Dubreuil S, Guerin B, Turcotte EE, Carpentier AC, Blondin DP. The effects of the beta1-adrenergic receptor antagonist bisoprolol administration on mirabegron-stimulated human brown adipose tissue thermogenesis. Acta Physiol (Oxf). 2024 May;240(5):e14127. doi: 10.1111/apha.14127. Epub 2024 Mar 19.
• Chunchai T, Chinchapo T, Sripetchwandee J, Thonusin C, Chattipakorn N, Chattipakorn SC. Lipopolysaccharide exacerbates depressive-like behaviors in obese rats through complement C1q-mediated synaptic elimination by microglia. Acta Physiol (Oxf). 2024 May;240(5):e14130. doi: 10.1111/apha.14130. Epub 2024 Mar 10.

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Indications