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Type: Artigo
Title: Chronic activation of γ2 AMPK induces obesity and reduces β cell function
Author: Yavari, Arash
Stocker, Claire J.
Ghaffari, Sahar
Wargent, Edward T.
Steeples, Violetta
Czibik, Gabor
Pinter, Katalin
Bellahcene, Mohamed
Woods, Angela
Morentin, Pablo B. Martínez de
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
Figueiredo, Márcio J. de Oliveira
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.
Arch, Jonathan R.S.
Cawthorne, Michael A.
Watkins, Hugh
Ashrafian, Houman
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
Subject: Obesidade
Country: Países Baixos
Editor: Elsevier
Rights: Fechado
Identifier DOI: 10.1016/j.cmet.2016.04.003
Date Issue: 2016
Appears in Collections:FCM - Artigos e Outros Documentos

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