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BIBTEX RIS

Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function

2016; Cell Press; Volume: 23; Issue: 5 Linguagem: Inglês

10.1016/j.cmet.2016.04.003

ISSN

1932-7420

Autores

Arash Yavari, Claire J. Stocker, Sahar Ghaffari, Edward T. Wargent, Violetta Steeples, Gábor Czibik, Katalin Pintér, Mohamed Bellahcene, Angela Woods, Pablo B. Martínez de Morentin, Céline Cansell, Brian Lam, André Chuster, Kasparas Petkevicius, Marie‐Sophie Nguyen‐Tu, Aida Martínez-Sánchez, Timothy J. Pullen, Peter L. Oliver, Alexander Stockenhuber, Chinh Nguyen, Merzaka Lazdam, Jacqueline O’Dowd, Parvathy E. Harikumar, Mónika Tóth, Craig Beall, Theodosios Kyriakou, Julia Parnis, Dhruv Sarma, George Katritsis, Diana D. J. Wortmann, Andrew R. Harper, Laurence A. Brown, Robin Willows, Silvia Gandra, Victor Augusto Poncio, Márcio Jansen de Oliveira Figueiredo, Nathan Qi, Stuart N. Peirson, Rory J. McCrimmon, Balázs Gereben, László Tretter, Csaba Fekete, Charles Redwood, Giles S.H. Yeo, Lora K. Heisler, Guy A. Rutter, Mark A. Smith, Dominic J. Withers, David Carling, Eduardo Back Sternick, Jonathan R.S. Arch, Michael A. Cawthorne, Hugh Watkins, Houman Ashrafian,

Tópico(s)

Regulation of Appetite and Obesity

Resumo

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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