Redox Biology (May 2021)
Sirt3 in POMC neurons controls energy balance in a sex- and diet-dependent manner
- Mar Quiñones,
- René Hernández-Bautista,
- Daniel Beiroa,
- Violeta Heras,
- Francisco L. Torres-Leal,
- Brian Y.H. Lam,
- Ana Senra,
- Johan Fernø,
- Alicia García Gómez-Valadés,
- Markus Schwaninger,
- Vincent Prevot,
- Giles Yeo,
- Marc Claret,
- Miguel López,
- Carlos Diéguez,
- Omar Al-Massadi,
- Ruben Nogueiras
Affiliations
- Mar Quiñones
- 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), 15706, Spain; Corresponding author. Centro de Investigaciones Médicas de la Universidad de Santiago (CIMUS), University of Santiago de Compostela & CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Avenida de Barcelona s/n, 15782, Santiago de Compostela (A Coruña), Spain.
- René Hernández-Bautista
- 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), 15706, Spain
- Daniel Beiroa
- 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), 15706, Spain
- Violeta Heras
- 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), 15706, Spain
- Francisco L. Torres-Leal
- Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; Metabolic Diseases, Exercise and Nutrition (DOMEN) Research Group, Federal University of Piauí, Teresina, Brazil
- Brian Y.H. Lam
- MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
- Ana Senra
- Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain
- Johan Fernø
- Hormone Laboratory, Haukeland University Hospital, Bergen, Norway
- Alicia García Gómez-Valadés
- Neuronal Control of Metabolism (NeuCoMe) Laboratory, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036, Barcelona, Spain
- Markus Schwaninger
- Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
- Vincent Prevot
- Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, European Genomic Institute for Diabetes (EGID), F-59000, Lille, France
- Giles Yeo
- MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
- Marc Claret
- Neuronal Control of Metabolism (NeuCoMe) Laboratory, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036, Barcelona, Spain; School of Medicine, Universitat de Barcelona, Barcelona, Spain
- Miguel López
- 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), 15706, Spain
- Carlos Diéguez
- 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), 15706, Spain
- Omar Al-Massadi
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain; Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Travesía da Choupana S/n, 15706, Santiago de Compostela, Spain; Corresponding author. Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain.
- Ruben Nogueiras
- 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), 15706, Spain; Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, Spain; Corresponding author. Centro de Investigaciones Médicas de la Universidad de Santiago (CIMUS), University of Santiago de Compostela & CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Avenida de Barcelona s/n, 15782, Santiago de Compostela (A Coruña), Spain.
- Journal volume & issue
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Vol. 41
p. 101945
Abstract
Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene that has emerged as an important player in the regulation of energy metabolism in peripheral tissues. However, its role in the hypothalamus has not been explored. Herein, we show that the genetic inhibition of SIRT3 in the hypothalamic arcuate nucleus (ARC) induced a negative energy balance and improvement of several metabolic parameters. These effects are specific for POMC neurons, because ablation of SIRT3 in POMC, but not in AgRP neurons, decreased body weight and adiposity, increased energy expenditure and brown adipose tissue (BAT) activity, and induced browning in white adipose tissue (WAT). Notably, the depletion of SIRT3 in POMC neurons caused these effects in male mice fed a chow diet but failed to affect energy balance in males fed a high fat diet and females under both type of diets. Overall, we provide the first evidence pointing for a key role of SIRT3 in POMC neurons in the regulation of energy balance.
