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Chronic Activation of γ2 AMPK Induces Obesity and Reduces ß Cell Function.
Yavari, Arash; Stocker, Claire J; Ghaffari, Sahar; Wargent, Edward T; Steeples, Violetta; Czibik, Gabor; Pinter, Katalin; Bellahcene, Mohamed; Woods, Angela; Martínez de Morentin, Pablo B; Cansell, Céline; Lam, Brian Y H; Chuster, André; Petkevicius, Kasparas; Nguyen-Tu, Marie-Sophie; Martinez-Sanchez, Aida; Pullen, Timothy J; Oliver, Peter L; Stockenhuber, Alexander; Nguyen, Chinh; Lazdam, Merzaka; O'Dowd, Jacqueline F; Harikumar, Parvathy; Tóth, Mónika; Beall, Craig; Kyriakou, Theodosios; Parnis, Julia; Sarma, Dhruv; Katritsis, George; Wortmann, Diana D J; Harper, Andrew R; Brown, Laurence A; Willows, Robin; Gandra, Silvia; Poncio, Victor; de Oliveira Figueiredo, Márcio J; Qi, Nathan R; Peirson, Stuart N; McCrimmon, Rory J; Gereben, Balázs; Tretter, László; Fekete, Csaba; Redwood, Charles; Yeo, Giles S H; Heisler, Lora K; Rutter, Guy A; Smith, Mark A; Withers, Dominic J; Carling, David; Sternick, Eduardo B.
Afiliación
  • Yavari A; Experimental Therapeutics, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
  • Stocker CJ; The Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
  • Ghaffari S; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Wargent ET; The Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
  • Steeples V; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Czibik G; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Pinter K; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Bellahcene M; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Woods A; Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College London, London SW7 2AZ, UK.
  • Martínez de Morentin PB; Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.
  • Cansell C; Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.
  • Lam BY; University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
  • Chuster A; Pos Graduação Ciências Médicas, Faculdade Ciências Médicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG 31270-901, Brazil.
  • Petkevicius K; University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
  • Nguyen-Tu MS; Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
  • Martinez-Sanchez A; Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
  • Pullen TJ; Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
  • Oliver PL; MRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, UK.
  • Stockenhuber A; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Nguyen C; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Lazdam M; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
  • O'Dowd JF; The Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
  • Harikumar P; The Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
  • Tóth M; Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
  • Beall C; Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK.
  • Kyriakou T; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Parnis J; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Sarma D; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Katritsis G; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Wortmann DD; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Harper AR; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Brown LA; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
  • Willows R; Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College London, London SW7 2AZ, UK.
  • Gandra S; Pos Graduação Ciências Médicas, Faculdade Ciências Médicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG 31270-901, Brazil.
  • Poncio V; Universidade Estadual de Campinas, Campinas-SP 13083-970, Brazil.
  • de Oliveira Figueiredo MJ; Universidade Estadual de Campinas, Campinas-SP 13083-970, Brazil.
  • Qi NR; Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Peirson SN; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
  • McCrimmon RJ; Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK.
  • Gereben B; Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
  • Tretter L; Department of Medical Biochemistry, Semmelweis University, Budapest 1085, Hungary; MTA-SE Laboratory for Neurobiochemistry, Semmelweis University, Budapest 1085, Hungary.
  • Fekete C; Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary; Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
  • Redwood C; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Yeo GS; University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
  • Heisler LK; Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.
  • Rutter GA; Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
  • Smith MA; Metabolic Signalling Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, UK.
  • Withers DJ; Metabolic Signalling Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, UK.
  • Carling D; Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College London, London SW7 2AZ, UK.
  • Sternick EB; Pos Graduação Ciências Médicas, Faculdade Ciências Médicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG 31270-901, Brazil.
Cell Metab ; 23(5): 821-36, 2016 May 10.
Article en En | MEDLINE | ID: mdl-27133129
ABSTRACT
Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Secretoras de Insulina / Proteínas Quinasas Activadas por AMP / Obesidad Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Secretoras de Insulina / Proteínas Quinasas Activadas por AMP / Obesidad Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido