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Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists
Aldosterone exerts deleterious effects on the cardiovascular system and promotes adipose tissue expansion via mineralocorticoid receptor (MR) activation. We previously demonstrated that administration of steroidal mineralocorticoid receptor antagonists (MRA) in mice fed a moderate high-fat diet is a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285041/ https://www.ncbi.nlm.nih.gov/pubmed/34272678 http://dx.doi.org/10.1007/s40618-021-01635-z |
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author | Marzolla, V. Feraco, A. Limana, F. Kolkhof, P. Armani, A. Caprio, M. |
author_facet | Marzolla, V. Feraco, A. Limana, F. Kolkhof, P. Armani, A. Caprio, M. |
author_sort | Marzolla, V. |
collection | PubMed |
description | Aldosterone exerts deleterious effects on the cardiovascular system and promotes adipose tissue expansion via mineralocorticoid receptor (MR) activation. We previously demonstrated that administration of steroidal mineralocorticoid receptor antagonists (MRA) in mice fed a moderate high-fat diet is able to reduce white adipose tissue (WAT) expansion, stimulate browning of WAT and activate interscapular brown adipose tissue (iBAT). Here, we aimed to compare the metabolic and adipose tissue-specific effects of the novel non-steroidal MRA finerenone (Fine) and spironolactone (Spiro) in a mouse model of very high-fat diet (HFD)-induced obesity. C57BL/6 J male mice were fed a 60% HFD containing or not Spiro or Fine for 12 weeks. WAT and iBAT morphology and adipose tissue gene expression analysis were assessed. After 12 weeks, both groups of mice showed similar weight gain compared to the HFD group. Histological and molecular analyses of WAT did not show significant differences among all experimental groups; differently, iBAT histological analysis revealed that Fine was able to increase recruitment of brown adipocytes in this depot, whereas mice treated with Spiro failed to elicit any iBAT response, as indicated by no changes in lipid droplets size and iBAT density, compared to HFD. Increased iBAT recruitment could explain, at least in part, the improved insulin resistance observed in mice treated with Fine, as shown by a significant reduction in homeostasis model assessment of insulin resistance (HOMA) index. These findings were confirmed by gene expression analysis of ucp-1, pgc1-α, and beta-3 adrenoreceptor (Adrb3) in iBAT, revealing significantly higher expression of these thermogenic genes in HFD + Fine group compared to HFD, whereas Spiro did not modify their expression. In summary, we demonstrated that, differently from Fine, Spiro did not induce iBAT recruitment. Our current study suggests that Fine, through its direct effects on iBAT, represents a promising pharmacologic tool to treat human metabolic diseases associated with adipose tissue dysfunctions. |
format | Online Article Text |
id | pubmed-8285041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-82850412021-07-19 Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists Marzolla, V. Feraco, A. Limana, F. Kolkhof, P. Armani, A. Caprio, M. J Endocrinol Invest Brief Report Aldosterone exerts deleterious effects on the cardiovascular system and promotes adipose tissue expansion via mineralocorticoid receptor (MR) activation. We previously demonstrated that administration of steroidal mineralocorticoid receptor antagonists (MRA) in mice fed a moderate high-fat diet is able to reduce white adipose tissue (WAT) expansion, stimulate browning of WAT and activate interscapular brown adipose tissue (iBAT). Here, we aimed to compare the metabolic and adipose tissue-specific effects of the novel non-steroidal MRA finerenone (Fine) and spironolactone (Spiro) in a mouse model of very high-fat diet (HFD)-induced obesity. C57BL/6 J male mice were fed a 60% HFD containing or not Spiro or Fine for 12 weeks. WAT and iBAT morphology and adipose tissue gene expression analysis were assessed. After 12 weeks, both groups of mice showed similar weight gain compared to the HFD group. Histological and molecular analyses of WAT did not show significant differences among all experimental groups; differently, iBAT histological analysis revealed that Fine was able to increase recruitment of brown adipocytes in this depot, whereas mice treated with Spiro failed to elicit any iBAT response, as indicated by no changes in lipid droplets size and iBAT density, compared to HFD. Increased iBAT recruitment could explain, at least in part, the improved insulin resistance observed in mice treated with Fine, as shown by a significant reduction in homeostasis model assessment of insulin resistance (HOMA) index. These findings were confirmed by gene expression analysis of ucp-1, pgc1-α, and beta-3 adrenoreceptor (Adrb3) in iBAT, revealing significantly higher expression of these thermogenic genes in HFD + Fine group compared to HFD, whereas Spiro did not modify their expression. In summary, we demonstrated that, differently from Fine, Spiro did not induce iBAT recruitment. Our current study suggests that Fine, through its direct effects on iBAT, represents a promising pharmacologic tool to treat human metabolic diseases associated with adipose tissue dysfunctions. Springer International Publishing 2021-07-16 2022 /pmc/articles/PMC8285041/ /pubmed/34272678 http://dx.doi.org/10.1007/s40618-021-01635-z Text en © Italian Society of Endocrinology (SIE) 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Brief Report Marzolla, V. Feraco, A. Limana, F. Kolkhof, P. Armani, A. Caprio, M. Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists |
title | Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists |
title_full | Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists |
title_fullStr | Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists |
title_full_unstemmed | Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists |
title_short | Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists |
title_sort | class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285041/ https://www.ncbi.nlm.nih.gov/pubmed/34272678 http://dx.doi.org/10.1007/s40618-021-01635-z |
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