title: Lack of Hypophagia in CB1 Null Mice is Associated to Decreased Hypothalamic POMC and CART Expression.
abstract: BACKGROUND
  Cumulative data indicate that the endocannabinoid system plays a major role in feeding behavior and energy balance. Genetic silencing of cannabinoid receptor type 1 (CB1) reduces body weight gain, independently of food intake.
  
  
  METHODS
  In this work, we investigated whether the hypothalamic neuropeptide expression pattern supports the absence of the anorexigenic response observed under constitutive CB1 ablation, by using neuronal CB1 conditional null mice (CamK-CB1-KO) and whole body CB1 null mice (CB1-KO).
  
  
  RESULTS
  Our data showed that both CB1 null models display a marked decrease in proopiomelanocortin (POMC) and cocaine-amphetamine-regulated transcript (CART) expression in the arcuate nucleus of the hypothalamus (ARC).
  
  
  CONCLUSIONS
  This evidence suggests that a lack of hypophagia is associated with the suppression of ARC anorexigenic neuropeptides and that behavioral changes in food intake (or lack thereof) after constitutive CB1 ablation are likely mediated by impaired melanocortin and CART signaling in the hypothalamus.
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane). ricardo.lage@usc.es m.lopez@usc.es.
authors: Ricardo
authors: R
authors: Lage
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Claudia
authors: C
authors: Parisi
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Patricia
authors: P
authors: Seoane-Collazo
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Johan
authors: J
authors: Fernø
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Roberta
authors: R
authors: Mazza
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Fátima
authors: F
authors: Bosch
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Luisa M
authors: LM
authors: Seoane
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Ruben
authors: R
authors: Nogueiras
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Carlos
authors: C
authors: Diéguez
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Carmelo
authors: C
authors: Quarta
authors: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain (Drs Lage, Parisi, Seoane-Collazo, Fernø, Nogueiras, Diéguez, and López); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain (Drs Lage, Seoane-Collazo, Seoane, Nogueiras, Diéguez, and López); Center of Animal Biotechnology and Gene Therapy and Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Spain (Drs Lage and Bosch); Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy (Drs Parisi, Mazza, and Quarta); Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, N-5020, Norway (Dr Fernø); Grupo Fisiopatología Endocrina, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, 15706, Spain (Dr Seoane).
authors: Miguel
authors: M
authors: López
mesh_terms: D000818:Animals; D000855:Anorexia / Q000378:metabolism*; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001522:Behavior, Animal; D001835:Body Weight; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D063387:Cannabinoid Receptor Antagonists; D009419:Nerve Tissue Proteins; D043884:Receptor, Cannabinoid, CB1; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin
keywords: CART; CB1; POMC; food intake; hypothalamus
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