Martins, LuisSeoane-Collazo, PatriciaContreras, CristinaGonzalez-Garcia, IsmaelMartinez-Sanchez, NoeliaGonzalez, FranciscoZalvide, JuanGallego, RosaliaDieguez, CarlosNogueiras, RubenTena-Sempere, ManuelLopez, Miguel2023-01-252023-01-252016-07-15Martins L, Seoane-Collazo P, Contreras C, González-García I, Martínez-Sánchez N, González F, et al. A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance. Cell Rep. 2016 Aug 23;16(8):2231-2242http://hdl.handle.net/10668/10359AMP-activated protein kinase (AMPK) in the ventromedial nucleus of the hypothalamus (VMH) and orexin (OX) in the lateral hypothalamic area (LHA) modulate brown adipose tissue (BAT) thermogenesis. However, whether these two molecular mechanisms act jointly or independently is unclear. Here, we show that the thermogenic effect of bone morphogenetic protein 8B (BMP8B) is mediated by the inhibition of AMPK in the VMH and the subsequent increase in OX signaling via the OX receptor 1 (OX1R). Accordingly, the thermogenic effect of BMP8B is totally absent in ox-null mice. BMP8B also induces browning of white adipose tissue (WAT), its thermogenic effect is sexually dimorphic (only observed in females), and its impact on OX expression and thermogenesis is abolished by the knockdown of glutamate vesicular transporter 2 (VGLUT2), implicating glutamatergic signaling. Overall, our data uncover a central network controlling energy homeostasis that may be of considerable relevance for obesity and metabolic disorders.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Orexin ReceptorsOrexinsRats, Sprague-DawleySex FactorsSignal TransductionThermogenesisVentromedial Hypothalamic NucleusVesicular Glutamate Transport Protein 2AMP-Activated Protein KinasesAdipose Tissue, BrownAdipose Tissue, WhiteAnimalsBody WeightBone Morphogenetic ProteinsEnergy MetabolismFemaleGene Expression RegulationGlutamic AcidHypothalamic Area, LateralMaleMice, Knockoutresearch article27524625open accessMetabolismo energéticoPeso corporalProteínas morfogenéticas óseasProteínas quinasas activadas por AMPRatones noqueadosRegulación de la expresión génicaTejido adiposo blanco10.1016/j.celrep.2016.07.0452211-1247PMC4999418http://www.cell.com/article/S2211124716309767/pdf