CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin
Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-10-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877814001306 |
| _version_ | 1818758984056700928 |
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| author | Pierre Cardinal Caroline André Carmelo Quarta Luigi Bellocchio Samantha Clark Melissa Elie Thierry Leste-Lasserre Marlene Maitre Delphine Gonzales Astrid Cannich Uberto Pagotto Giovanni Marsicano Daniela Cota |
| author_facet | Pierre Cardinal Caroline André Carmelo Quarta Luigi Bellocchio Samantha Clark Melissa Elie Thierry Leste-Lasserre Marlene Maitre Delphine Gonzales Astrid Cannich Uberto Pagotto Giovanni Marsicano Daniela Cota |
| author_sort | Pierre Cardinal |
| collection | DOAJ |
| description | Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change. |
| first_indexed | 2024-12-18T06:35:30Z |
| format | Article |
| id | doaj.art-9326a8123b5d476ba5f3994c9b1769e7 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-18T06:35:30Z |
| publishDate | 2014-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-9326a8123b5d476ba5f3994c9b1769e72022-12-21T21:17:47ZengElsevierMolecular Metabolism2212-87782014-10-013770571610.1016/j.molmet.2014.07.004CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptinPierre Cardinal0Caroline André1Carmelo Quarta2Luigi Bellocchio3Samantha Clark4Melissa Elie5Thierry Leste-Lasserre6Marlene Maitre7Delphine Gonzales8Astrid Cannich9Uberto Pagotto10Giovanni Marsicano11Daniela Cota12INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceEndocrinology Unit and Centro Unificato di Ricerca BioMedica Applicata, Dept. of Clinical Medicine, University of Bologna, I-40138 Bologna, ItalyINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceEndocrinology Unit and Centro Unificato di Ricerca BioMedica Applicata, Dept. of Clinical Medicine, University of Bologna, I-40138 Bologna, ItalyINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceINSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, FranceMetabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.http://www.sciencedirect.com/science/article/pii/S2212877814001306CB1 receptorEndocannabinoidVentromedial nucleusHypothalamusObesityLeptin |
| spellingShingle | Pierre Cardinal Caroline André Carmelo Quarta Luigi Bellocchio Samantha Clark Melissa Elie Thierry Leste-Lasserre Marlene Maitre Delphine Gonzales Astrid Cannich Uberto Pagotto Giovanni Marsicano Daniela Cota CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin Molecular Metabolism CB1 receptor Endocannabinoid Ventromedial nucleus Hypothalamus Obesity Leptin |
| title | CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin |
| title_full | CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin |
| title_fullStr | CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin |
| title_full_unstemmed | CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin |
| title_short | CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin |
| title_sort | cb1 cannabinoid receptor in sf1 expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin |
| topic | CB1 receptor Endocannabinoid Ventromedial nucleus Hypothalamus Obesity Leptin |
| url | http://www.sciencedirect.com/science/article/pii/S2212877814001306 |
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