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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.
Afiliación
  • Rial-Pensado E; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Freire-Agulleiro O; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Ríos M; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Guo DF; Department of Neuroscience & Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
  • Contreras C; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Seoane-Collazo P; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Tovar S; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Nogueiras R; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Diéguez C; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Rahmouni K; Department of Neuroscience & Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA. Electronic address: kamal-rahmouni@uiowa.edu.
  • López M; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain. Electronic address: m.lopez@usc.es.
Mol Metab ; 59: 101465, 2022 05.
Article en En | MEDLINE | ID: mdl-35218946
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tejido Adiposo Pardo / Proteínas Morfogenéticas Óseas / Termogénesis Límite: Animals Idioma: En Revista: Mol Metab Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tejido Adiposo Pardo / Proteínas Morfogenéticas Óseas / Termogénesis Límite: Animals Idioma: En Revista: Mol Metab Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Alemania