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Hypothalamic dopamine signaling regulates brown fat thermogenesis.

  • Folgueira C Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo. Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria, Santiago de Compostela, Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain.
  • Beiroa D CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Porteiro B CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Duquenne M Jean-Pierre Aubert Research Center (JPArc), Laboratory of Development and Plasticity of the Neuroendocrine Brain, Inserm UMR-S 1172, Lille, France.
  • Puighermanal E IGF, Inserm, CNRS, Univ. Montpellier, F-34094 Montpellier, France.
  • Fondevila MF CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Barja-Fernández S Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo. Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria, Santiago de Compostela, Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain.
  • Gallego R Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela, S. Francisco s/n, 15782 Santiago de Compostela (A Coruña), Spain.
  • Hernández-Bautista R CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Castelao C Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo. Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria, Santiago de Compostela, Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain.
  • Senra A CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Seoane P CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Gómez N Molecular Imaging Group, Department of Psychiatry, Radiology and Public Health, Faculty of Medicine Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782 Spain; Molecular Imaging Group. Health Research Institute of Santiago de Compostela (IDIS). Travesía da Choupana s/n Santiago de Compostela. Zip Code: 15706. Spain; Nuclear Medicine Department University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n. Santiago de Compostela 15706 Spain.
  • Aguiar P Molecular Imaging Group, Department of Psychiatry, Radiology and Public Health, Faculty of Medicine Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782 Spain; Molecular Imaging Group. Health Research Institute of Santiago de Compostela (IDIS). Travesía da Choupana s/n Santiago de Compostela. Zip Code: 15706. Spain; Nuclear Medicine Department University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n. Santiago de Compostela 15706 Spain.
  • Guallar D CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Fidalgo M CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Romero-Pico A CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Adan R Brain Center Rudolf Magnus, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
  • Blouet C MRC Metabolic Disease Unit. Institute of Metabolic Science. University of Cambridge, UK.
  • Labandeira-García JL CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Jeanrenaud F Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • Kallo I Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, HAS, 1083, Budapest, Hungary.
  • Liposits Z Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, HAS, 1083, Budapest, Hungary.
  • Salvador J CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Prevot V Jean-Pierre Aubert Research Center (JPArc), Laboratory of Development and Plasticity of the Neuroendocrine Brain, Inserm UMR-S 1172, Lille, France.
  • Dieguez C CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Lopez M CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
  • Valjent E IGF, Inserm, CNRS, Univ. Montpellier, F-34094 Montpellier, France.
  • Frühbeck G CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Seoane LM Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo. Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria, Santiago de Compostela, Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain.
  • Nogueiras R CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
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  • 2019-10-04
Published in:
  • Nature metabolism. - 2019
English Dopamine signaling is a crucial part of the brain reward system and can affect feeding behavior. Dopamine receptors are also expressed in the hypothalamus, which is known to control energy metabolism in peripheral tissues. Here we show that pharmacological or chemogenetic stimulation of dopamine receptor 2 (D2R) expressing cells in the lateral hypothalamic area (LHA) and the zona incerta (ZI) decreases body weight and stimulates brown fat activity in rodents in a feeding-independent manner. LHA/ZI D2R stimulation requires an intact sympathetic nervous system and orexin system to exert its action and involves inhibition of PI3K in the LHA/ZI. We further demonstrate that, as early as 3 months after onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the CNS to regulate energy balance.
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https://sonar.ch/global/documents/232604
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