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Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome

OBJECTIVE: Bone morphogenetic protein 8B (BMP8B) plays a major role in the regulation of energy homeostasis by modulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. Here, we investigated whether BMP8B's role in metabolism is affected by obesity and the pos...

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Autores principales: Rial-Pensado, Eva, Freire-Agulleiro, Oscar, Ríos, Marcos, Guo, Deng Fu, Contreras, Cristina, Seoane-Collazo, Patricia, Tovar, Sulay, Nogueiras, Rubén, Diéguez, Carlos, Rahmouni, Kamal, López, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933534/
https://www.ncbi.nlm.nih.gov/pubmed/35218946
http://dx.doi.org/10.1016/j.molmet.2022.101465
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author Rial-Pensado, Eva
Freire-Agulleiro, Oscar
Ríos, Marcos
Guo, Deng Fu
Contreras, Cristina
Seoane-Collazo, Patricia
Tovar, Sulay
Nogueiras, Rubén
Diéguez, Carlos
Rahmouni, Kamal
López, Miguel
author_facet Rial-Pensado, Eva
Freire-Agulleiro, Oscar
Ríos, Marcos
Guo, Deng Fu
Contreras, Cristina
Seoane-Collazo, Patricia
Tovar, Sulay
Nogueiras, Rubén
Diéguez, Carlos
Rahmouni, Kamal
López, Miguel
author_sort Rial-Pensado, Eva
collection PubMed
description OBJECTIVE: Bone morphogenetic protein 8B (BMP8B) plays a major role in the regulation of energy homeostasis by modulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. Here, we investigated whether BMP8B's role in metabolism is affected by obesity and the possible molecular mechanisms underlying that action. METHODS: Central treatments with BMP8B were performed in rats fed a standard (SD) and high-fat diet (HFD), as well as in genetically modified mice. Energy balance studies, infrared thermographic analysis of BAT and molecular analysis of the hypothalamus, BAT and WAT were carried out. RESULTS: We show for the first time that HFD-induced obesity elicits resistance to the central actions of BMP8B on energy balance. This obesity-induced BMP8B resistance is explained by i) lack of effects on AMP-activated protein kinase (AMPK) signaling, ii) decreased BMP receptors signaling and iii) reduced expression of Bardet-Biedl Syndrome 1 (BBS1) protein, a key component of the protein complex BBSome in the ventromedial nucleus of the hypothalamus (VMH). The possible mechanistic involvement of BBS1 in this process is demonstrated by lack of a central response to BMP8B in mice carrying a single missense disease-causing mutation in the Bbs1 gene. CONCLUSIONS: Overall, our data uncover a new mechanism of central resistance to hormonal action that may be of relevance in the pathophysiology of obesity.
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spelling pubmed-89335342022-03-20 Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome Rial-Pensado, Eva Freire-Agulleiro, Oscar Ríos, Marcos Guo, Deng Fu Contreras, Cristina Seoane-Collazo, Patricia Tovar, Sulay Nogueiras, Rubén Diéguez, Carlos Rahmouni, Kamal López, Miguel Mol Metab Original Article OBJECTIVE: Bone morphogenetic protein 8B (BMP8B) plays a major role in the regulation of energy homeostasis by modulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. Here, we investigated whether BMP8B's role in metabolism is affected by obesity and the possible molecular mechanisms underlying that action. METHODS: Central treatments with BMP8B were performed in rats fed a standard (SD) and high-fat diet (HFD), as well as in genetically modified mice. Energy balance studies, infrared thermographic analysis of BAT and molecular analysis of the hypothalamus, BAT and WAT were carried out. RESULTS: We show for the first time that HFD-induced obesity elicits resistance to the central actions of BMP8B on energy balance. This obesity-induced BMP8B resistance is explained by i) lack of effects on AMP-activated protein kinase (AMPK) signaling, ii) decreased BMP receptors signaling and iii) reduced expression of Bardet-Biedl Syndrome 1 (BBS1) protein, a key component of the protein complex BBSome in the ventromedial nucleus of the hypothalamus (VMH). The possible mechanistic involvement of BBS1 in this process is demonstrated by lack of a central response to BMP8B in mice carrying a single missense disease-causing mutation in the Bbs1 gene. CONCLUSIONS: Overall, our data uncover a new mechanism of central resistance to hormonal action that may be of relevance in the pathophysiology of obesity. Elsevier 2022-02-23 /pmc/articles/PMC8933534/ /pubmed/35218946 http://dx.doi.org/10.1016/j.molmet.2022.101465 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Rial-Pensado, Eva
Freire-Agulleiro, Oscar
Ríos, Marcos
Guo, Deng Fu
Contreras, Cristina
Seoane-Collazo, Patricia
Tovar, Sulay
Nogueiras, Rubén
Diéguez, Carlos
Rahmouni, Kamal
López, Miguel
Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
title Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
title_full Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
title_fullStr Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
title_full_unstemmed Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
title_short Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
title_sort obesity induces resistance to central action of bmp8b through a mechanism involving the bbsome
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933534/
https://www.ncbi.nlm.nih.gov/pubmed/35218946
http://dx.doi.org/10.1016/j.molmet.2022.101465
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