The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1111/1440-1681.13566 http://hdl.handle.net/11449/233381 |
Resumo: | Mirabegron is a selective β₃-adrenergic receptors agonist, which has been recently shown to improve metabolic health in rodents and humans. In this study, we investigated the effects of 2-week mirabegron treatment on the metabolic parameters of mice with a diet-induced obesity (DIO). C57BL/6JUnib mice were divided into control (CTR) and obese (OB) groups treated with vehicle, and an OB group treated with mirabegron (OB + MIRA). The obese groups were fed a high-fat diet for 12 weeks. Mirabegron (10 mg/kg/day) was administrated orally by gavage from weeks 10–12. After 2 weeks of mirabegron treatment, the energy expenditure was assessed with indirect calorimetry. Blood glucose, insulin, glycerol, free fatty acids (FFA), thiobarbituric acid reactive substance (TBAR), and tumour necrosis factor (TNF)-α levels were also assessed, and the HOMA index was determined. Liver tissue, brown adipose tissue (BAT), and inguinal white adipose tissue (iWAT) samples were collected for histological examination. The protein expressions of uncoupling protein 1 (UCP1) and mitochondrial transcription factor A (TFAM) were assessed using western blotting of the BAT and iWAT samples. In this study, mirabegron increased the energy expenditure and decreased adiposity in OB + MIRA. Increased UCP1 expression in BAT without changes in iWAT was also found. Mirabegron decreased circulating levels of FFA, glycerol, insulin, TNF-α, TBARS and HOMA index. DIO significantly increased the lipid deposits in the liver and BAT, but mirabegron partially reversed this change. Our findings indicate that treatment with mirabegron decreased inflammation and improved metabolism in obese mice. This effect was associated with increased BAT-mediated energy expenditure, but not iWAT beiging, which suggests that mirabegron might be useful for the treatment of obesity and diabetes. |
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The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissuebeigingbrown adipose tissueinflammationinsulin resistancemirabegronobesityβ₃-AR agonistMirabegron is a selective β₃-adrenergic receptors agonist, which has been recently shown to improve metabolic health in rodents and humans. In this study, we investigated the effects of 2-week mirabegron treatment on the metabolic parameters of mice with a diet-induced obesity (DIO). C57BL/6JUnib mice were divided into control (CTR) and obese (OB) groups treated with vehicle, and an OB group treated with mirabegron (OB + MIRA). The obese groups were fed a high-fat diet for 12 weeks. Mirabegron (10 mg/kg/day) was administrated orally by gavage from weeks 10–12. After 2 weeks of mirabegron treatment, the energy expenditure was assessed with indirect calorimetry. Blood glucose, insulin, glycerol, free fatty acids (FFA), thiobarbituric acid reactive substance (TBAR), and tumour necrosis factor (TNF)-α levels were also assessed, and the HOMA index was determined. Liver tissue, brown adipose tissue (BAT), and inguinal white adipose tissue (iWAT) samples were collected for histological examination. The protein expressions of uncoupling protein 1 (UCP1) and mitochondrial transcription factor A (TFAM) were assessed using western blotting of the BAT and iWAT samples. In this study, mirabegron increased the energy expenditure and decreased adiposity in OB + MIRA. Increased UCP1 expression in BAT without changes in iWAT was also found. Mirabegron decreased circulating levels of FFA, glycerol, insulin, TNF-α, TBARS and HOMA index. DIO significantly increased the lipid deposits in the liver and BAT, but mirabegron partially reversed this change. Our findings indicate that treatment with mirabegron decreased inflammation and improved metabolism in obese mice. This effect was associated with increased BAT-mediated energy expenditure, but not iWAT beiging, which suggests that mirabegron might be useful for the treatment of obesity and diabetes.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Wexner Medical CenterDepartment of Physiology and Cell Biology The Ohio State University Wexner Medical CenterDepartment of Physical Education Institute of Biosciences São Paulo State University (UNESP)Department of Pharmacology Faculty of Medical Sciences University of Campinas (UNICAMP)Department of Structural and Functional Biology Institute of Biology University of Campinas (UNICAMP)Medical School Graduate Program in Environmental Health Metropolitan University of SantosDepartment of Physical Education Institute of Biosciences São Paulo State University (UNESP)The Ohio State University Wexner Medical CenterUniversidade Estadual Paulista (UNESP)Universidade Estadual de Campinas (UNICAMP)Metropolitan University of SantosPeres Valgas da Silva, Carmem [UNESP]Calmasini, FabianoAlexandre, Eduardo CostaRaposo, Helena FonsecaDelbin, Maria AndreiaMonica, Fabiola ZakiaZanesco, Angelina [UNESP]2022-05-01T08:15:12Z2022-05-01T08:15:12Z2021-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1477-1487http://dx.doi.org/10.1111/1440-1681.13566Clinical and Experimental Pharmacology and Physiology, v. 48, n. 11, p. 1477-1487, 2021.1440-16810305-1870http://hdl.handle.net/11449/23338110.1111/1440-1681.135662-s2.0-85112390164Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengClinical and Experimental Pharmacology and Physiologyinfo:eu-repo/semantics/openAccess2022-05-01T08:15:13Zoai:repositorio.unesp.br:11449/233381Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:50:53.032211Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue |
title |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue |
spellingShingle |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue Peres Valgas da Silva, Carmem [UNESP] beiging brown adipose tissue inflammation insulin resistance mirabegron obesity β₃-AR agonist |
title_short |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue |
title_full |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue |
title_fullStr |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue |
title_full_unstemmed |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue |
title_sort |
The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue |
author |
Peres Valgas da Silva, Carmem [UNESP] |
author_facet |
Peres Valgas da Silva, Carmem [UNESP] Calmasini, Fabiano Alexandre, Eduardo Costa Raposo, Helena Fonseca Delbin, Maria Andreia Monica, Fabiola Zakia Zanesco, Angelina [UNESP] |
author_role |
author |
author2 |
Calmasini, Fabiano Alexandre, Eduardo Costa Raposo, Helena Fonseca Delbin, Maria Andreia Monica, Fabiola Zakia Zanesco, Angelina [UNESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
The Ohio State University Wexner Medical Center Universidade Estadual Paulista (UNESP) Universidade Estadual de Campinas (UNICAMP) Metropolitan University of Santos |
dc.contributor.author.fl_str_mv |
Peres Valgas da Silva, Carmem [UNESP] Calmasini, Fabiano Alexandre, Eduardo Costa Raposo, Helena Fonseca Delbin, Maria Andreia Monica, Fabiola Zakia Zanesco, Angelina [UNESP] |
dc.subject.por.fl_str_mv |
beiging brown adipose tissue inflammation insulin resistance mirabegron obesity β₃-AR agonist |
topic |
beiging brown adipose tissue inflammation insulin resistance mirabegron obesity β₃-AR agonist |
description |
Mirabegron is a selective β₃-adrenergic receptors agonist, which has been recently shown to improve metabolic health in rodents and humans. In this study, we investigated the effects of 2-week mirabegron treatment on the metabolic parameters of mice with a diet-induced obesity (DIO). C57BL/6JUnib mice were divided into control (CTR) and obese (OB) groups treated with vehicle, and an OB group treated with mirabegron (OB + MIRA). The obese groups were fed a high-fat diet for 12 weeks. Mirabegron (10 mg/kg/day) was administrated orally by gavage from weeks 10–12. After 2 weeks of mirabegron treatment, the energy expenditure was assessed with indirect calorimetry. Blood glucose, insulin, glycerol, free fatty acids (FFA), thiobarbituric acid reactive substance (TBAR), and tumour necrosis factor (TNF)-α levels were also assessed, and the HOMA index was determined. Liver tissue, brown adipose tissue (BAT), and inguinal white adipose tissue (iWAT) samples were collected for histological examination. The protein expressions of uncoupling protein 1 (UCP1) and mitochondrial transcription factor A (TFAM) were assessed using western blotting of the BAT and iWAT samples. In this study, mirabegron increased the energy expenditure and decreased adiposity in OB + MIRA. Increased UCP1 expression in BAT without changes in iWAT was also found. Mirabegron decreased circulating levels of FFA, glycerol, insulin, TNF-α, TBARS and HOMA index. DIO significantly increased the lipid deposits in the liver and BAT, but mirabegron partially reversed this change. Our findings indicate that treatment with mirabegron decreased inflammation and improved metabolism in obese mice. This effect was associated with increased BAT-mediated energy expenditure, but not iWAT beiging, which suggests that mirabegron might be useful for the treatment of obesity and diabetes. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-11-01 2022-05-01T08:15:12Z 2022-05-01T08:15:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1111/1440-1681.13566 Clinical and Experimental Pharmacology and Physiology, v. 48, n. 11, p. 1477-1487, 2021. 1440-1681 0305-1870 http://hdl.handle.net/11449/233381 10.1111/1440-1681.13566 2-s2.0-85112390164 |
url |
http://dx.doi.org/10.1111/1440-1681.13566 http://hdl.handle.net/11449/233381 |
identifier_str_mv |
Clinical and Experimental Pharmacology and Physiology, v. 48, n. 11, p. 1477-1487, 2021. 1440-1681 0305-1870 10.1111/1440-1681.13566 2-s2.0-85112390164 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Clinical and Experimental Pharmacology and Physiology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1477-1487 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129257314975744 |