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Cell Rep. 2016 Aug 23;16(8):2231-2242. doi: 10.1016/j.celrep.2016.07.045. Epub 2016 Aug 11.

A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance.

Author information

1
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), Santiago de Compostela 15706, Spain.
2
Department of Surgery, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; Service of Ophthalmology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela 15706, Spain.
3
Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
4
Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
5
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Córdoba, Spain; Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Reina Sofía, 14004 Córdoba, Spain; FiDiPro Program, Department of Physiology, University of Turku, Kiinamyllynkatu10, 20520 Turku, Finland.
6
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), Santiago de Compostela 15706, Spain. Electronic address: m.lopez@usc.es.

Abstract

AMP-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.

PMID:
27524625
PMCID:
PMC4999418
DOI:
10.1016/j.celrep.2016.07.045
[Indexed for MEDLINE]
Free PMC Article

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