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

Eva Rial-Pensado; Oscar Freire-Agulleiro; Marcos Ríos; Deng Fu Guo; Cristina Contreras; Patricia Seoane-Collazo; Sulay Tovar; Rubén Nogueiras; Carlos Diéguez; Kamal Rahmouni; Miguel López

doi:10.1016/j.molmet.2022.101465

Back

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

Journal article

Open access

Peer reviewed

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

Eva Rial-Pensado, Oscar Freire-Agulleiro, Marcos Ríos, Deng Fu Guo, Cristina Contreras, Patricia Seoane-Collazo, Sulay Tovar, Rubén Nogueiras, Carlos Diéguez, Kamal Rahmouni, …

Molecular metabolism, Vol.59, 101465

02/23/2022

DOI: 10.1016/j.molmet.2022.101465

PMCID: PMC8933534

PMID: 35218946

Files and links (1)

url

https://doi.org/10.1016/j.molmet.2022.101465View

Published (Version of record) Open Access

Abstract

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 role in metabolism is affected by obesity and the possible molecular mechanisms underlying that action. Central treatments with BMP8B were performed in rats fed standard (SD) and high fat diet (HFD), as well as in genetic modified mice. Energy balance studies, infrared thermographic analysis of BAT and molecular analysis of the hypothalamus, BAT and WAT were carried out. 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 central response to BMP8B in mice carrying a single missense disease-causing mutation in the Bbs1 gene. Overall, our data uncover a new mechanism of central resistance to hormonal action that may be of relevance in the pathophysiology of obesity.

Obesity

BBS1

AMPK

BMP8B

BAT

hypothalamus

Details

Title: Subtitle: Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
Creators: Eva Rial-Pensado - 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
Oscar Freire-Agulleiro - 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
Marcos Ríos - 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
Deng Fu Guo - Department of Neuroscience & Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Cristina Contreras - 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
Patricia Seoane-Collazo - 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
Sulay Tovar - 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
Rubén Nogueiras - 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
Carlos Diéguez - 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
Kamal Rahmouni - Department of Neuroscience & Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address: kamal-rahmouni@uiowa.edu
Miguel López - 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
Resource Type: Journal article
Publication Details: Molecular metabolism, Vol.59, 101465
DOI: 10.1016/j.molmet.2022.101465
PMID: 35218946
PMCID: PMC8933534
NLM abbreviation: Mol Metab
ISSN: 2212-8778
Language: English
Date published: 02/23/2022
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984222737202771

Metrics

54 Record Views

12 Times Cited - Web of Science