SF1-Specific AMPKα1 Deletion Protects Against Diet-Induced Obesity.

Autor: Seoane-Collazo P; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Roa J; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain., Rial-Pensado E; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Liñares-Pose L; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Beiroa D; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Ruíz-Pino F; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain., López-González T; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Morgan DA; Department of Pharmacology, University of Iowa, Iowa City, IA., Pardavila JÁ; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain., Sánchez-Tapia MJ; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain., Martínez-Sánchez N; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Contreras C; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Fidalgo M; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain., Diéguez C; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Coppari R; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Diabetes Center of the Faculty of Medicine, University of Geneva, Geneva, Switzerland., Rahmouni K; Department of Pharmacology, University of Iowa, Iowa City, IA.; Department of Internal Medicine, University of Iowa, Iowa City, IA., Nogueiras R; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain., Tena-Sempere M; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica (IMIBIC)/Hospital Universitario Reina Sofía, Córdoba, Spain.; FiDiPro Program, Institute of Biomedicine, University of Turku, Turku, Finland., López M; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain m.lopez@usc.es.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.
Jazyk: angličtina
Zdroj: Diabetes [Diabetes] 2018 Nov; Vol. 67 (11), pp. 2213-2226. Date of Electronic Publication: 2018 Aug 13.
DOI: 10.2337/db17-1538
Abstrakt: AMPK is a cellular gauge that is activated under conditions of low energy, increasing energy production and reducing energy waste. Current evidence links hypothalamic AMPK with the central regulation of energy balance. However, it is unclear whether targeting hypothalamic AMPK has beneficial effects in obesity. Here, we show that genetic inhibition of AMPK in the ventromedial nucleus of the hypothalamus (VMH) protects against high-fat diet (HFD)-induced obesity by increasing brown adipose tissue (BAT) thermogenesis and subsequently energy expenditure. Notably, this effect depends upon the AMPKα1 isoform in steroidogenic factor 1 (SF1) neurons of the VMH, since mice bearing selective ablation of AMPKα1 in SF1 neurons display resistance to diet-induced obesity, increased BAT thermogenesis, browning of white adipose tissue, and improved glucose and lipid homeostasis. Overall, our findings point to hypothalamic AMPK in specific neuronal populations as a potential druggable target for the treatment of obesity and associated metabolic disorders.
(© 2018 by the American Diabetes Association.)
Databáze: MEDLINE