RT Journal Article
T1 Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome
A1 Rial Pensado, Eva
A1 Freire-Agulleiro, Óscar
A1 Ríos García, Marcos
A1 Guo, Deng Fu
A1 Contreras Jiménez, Cristina
A1 Seoane Collazo, Patricia
A1 Tovar, Sulay
A1 Nogueiras Pozo, Rubén
A1 Diéguez González, Carlos
A1 Rahmouni, Kamal
A1 López Pérez, Miguel A.
K1 Obesity
K1 Hypothalamus
K1 AMPK
K1 BAT
K1 BMP8B
K1 BBS1
AB 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
PB Elsevier
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29037
UL http://hdl.handle.net/10347/29037
LA eng
NO Molecular Metabolism 59 (2022) 101465
NO The research leading to these results received funding from the Xunta de Galicia (RN: 2016-PG057); Ministerio de Ciencia e Innovación co-funded by the FEDER Program of EU (CD: BFU2017-87721; RN: BFU2015-70664R; ML: RTI2018–101840-B-I00); USA National Institutes of Health (KR: HL084207); the USA Department of Veterans Affairs (KR: I01BX004249); The University of Iowa Fraternal Order of Eagles Diabetes Research Center (KR); European Research Council (ERC Synergy Grant-2019-WATCH- 810331); Atresmedia Corporación (RN and ML: 2017-PO004) and “la Caixa” Foundation (ID 100010434) under agreement LCF/PR/HR19/52160022 (ML). CiMUS is supported by the Xunta de Galicia (2016–2019, ED431G/05).OF-A is recipeint of a fellowship of Xunta de Galicia (ED481A-2019/026). PS-C is recipient of a fellowship the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie actions
DS Minerva
RD 30 abr 2026