The combined effect of metformin and mirabegron on diet‐induced obesity
Abstract Anti‐obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti‐obesity effects during concurrent use of both have yet to be explored. In th...
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.207 |
| _version_ | 1797849274022625280 |
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| author | Xin‐Yuan Zhao Ying Liu Xuan Zhang Ben‐Chi Zhao George Burley Zhi‐Can Yang Yi Luo An‐Qi Li Ruo‐Xin Zhang Zhi‐Ying Liu Yan‐Chuan Shi Qiao‐Ping Wang |
| author_facet | Xin‐Yuan Zhao Ying Liu Xuan Zhang Ben‐Chi Zhao George Burley Zhi‐Can Yang Yi Luo An‐Qi Li Ruo‐Xin Zhang Zhi‐Ying Liu Yan‐Chuan Shi Qiao‐Ping Wang |
| author_sort | Xin‐Yuan Zhao |
| collection | DOAJ |
| description | Abstract Anti‐obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti‐obesity effects during concurrent use of both have yet to be explored. In this study, we investigated the anti‐obesity effects, metabolic benefits, and underlying mechanisms of Met/Mir combination therapy in two clinically relevant contexts: the prevention model and the treatment model. In the prevention model, Met/Mir caused further 12% and 14% reductions in body weight (BW) gain induced by a high‐fat diet compared to Met or Mir alone, respectively. In the treatment model, Met/Mir additively promoted 17% BW loss in diet‐induced obese mice, which was 13% and 6% greater than Met and Mir alone, respectively. Additionally, Met/Mir improved glucose tolerance and insulin sensitivity. These benefits of Met/Mir were associated with increased EE, activated brown adipose tissue thermogenesis, and white adipose tissue browning. Significantly, Met/Mir did not cause cardiovascular dysfunction in either model. Together, the combination of Met and Mir could be a promising approach for the prevention and treatment of obesity by targeting both EI and EE simultaneously. |
| first_indexed | 2024-04-09T18:41:14Z |
| format | Article |
| id | doaj.art-e98806f50d984fd699939b3df1646c3f |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-04-09T18:41:14Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-e98806f50d984fd699939b3df1646c3f2023-04-11T05:24:31ZengWileyMedComm2688-26632023-04-0142n/an/a10.1002/mco2.207The combined effect of metformin and mirabegron on diet‐induced obesityXin‐Yuan Zhao0Ying Liu1Xuan Zhang2Ben‐Chi Zhao3George Burley4Zhi‐Can Yang5Yi Luo6An‐Qi Li7Ruo‐Xin Zhang8Zhi‐Ying Liu9Yan‐Chuan Shi10Qiao‐Ping Wang11Laboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaObesity and Metabolic Disease Research Group Diabetes and Metabolism Division Garvan Institute of Medical Research Sydney New South Wales AustraliaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaObesity and Metabolic Disease Research Group Diabetes and Metabolism Division Garvan Institute of Medical Research Sydney New South Wales AustraliaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaObesity and Metabolic Disease Research Group Diabetes and Metabolism Division Garvan Institute of Medical Research Sydney New South Wales AustraliaLaboratory of Metabolism and AgingSchool of Pharmaceutical Sciences (Shenzhen)Shenzhen Campus of Sun Yat‐sen UniversitySun Yat‐sen University ShenzhenChinaAbstract Anti‐obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti‐obesity effects during concurrent use of both have yet to be explored. In this study, we investigated the anti‐obesity effects, metabolic benefits, and underlying mechanisms of Met/Mir combination therapy in two clinically relevant contexts: the prevention model and the treatment model. In the prevention model, Met/Mir caused further 12% and 14% reductions in body weight (BW) gain induced by a high‐fat diet compared to Met or Mir alone, respectively. In the treatment model, Met/Mir additively promoted 17% BW loss in diet‐induced obese mice, which was 13% and 6% greater than Met and Mir alone, respectively. Additionally, Met/Mir improved glucose tolerance and insulin sensitivity. These benefits of Met/Mir were associated with increased EE, activated brown adipose tissue thermogenesis, and white adipose tissue browning. Significantly, Met/Mir did not cause cardiovascular dysfunction in either model. Together, the combination of Met and Mir could be a promising approach for the prevention and treatment of obesity by targeting both EI and EE simultaneously.https://doi.org/10.1002/mco2.207β3‐adrenergic receptor agonistcombination therapy for obesityenergy expenditurefood intakemetforminthermogenesis |
| spellingShingle | Xin‐Yuan Zhao Ying Liu Xuan Zhang Ben‐Chi Zhao George Burley Zhi‐Can Yang Yi Luo An‐Qi Li Ruo‐Xin Zhang Zhi‐Ying Liu Yan‐Chuan Shi Qiao‐Ping Wang The combined effect of metformin and mirabegron on diet‐induced obesity MedComm β3‐adrenergic receptor agonist combination therapy for obesity energy expenditure food intake metformin thermogenesis |
| title | The combined effect of metformin and mirabegron on diet‐induced obesity |
| title_full | The combined effect of metformin and mirabegron on diet‐induced obesity |
| title_fullStr | The combined effect of metformin and mirabegron on diet‐induced obesity |
| title_full_unstemmed | The combined effect of metformin and mirabegron on diet‐induced obesity |
| title_short | The combined effect of metformin and mirabegron on diet‐induced obesity |
| title_sort | combined effect of metformin and mirabegron on diet induced obesity |
| topic | β3‐adrenergic receptor agonist combination therapy for obesity energy expenditure food intake metformin thermogenesis |
| url | https://doi.org/10.1002/mco2.207 |
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