Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.
| Title: | Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function. |
|---|---|
| Authors: | A Yavari; CJ Stocker; S Ghaffari; ET Wargent; V Steeples; G Czibik; K Pinter; M Bellahcene; A Woods; PB Martínez de Morentin; C Cansell; BY Lam; A Chuster; K Petkevicius; MS Nguyen-Tu; A Martinez-Sanchez; TJ Pullen; PL Oliver; A Stockenhuber; C Nguyen; M Lazdam; JF O'Dowd; P Harikumar; M Tóth; C Beall; T Kyriakou; J Parnis; D Sarma; G Katritsis; DD Wortmann; AR Harper; LA Brown; R Willows; S Gandra; V Poncio; MJ de Oliveira Figueiredo; NR Qi; SN Peirson; RJ McCrimmon; B Gereben; L Tretter; C Fekete; C Redwood; GS Yeo; LK Heisler; GA Rutter; MA Smith; DJ Withers; D Carling; EB Sternick; JR Arch; MA Cawthorne; H Watkins; H Ashrafian |
| Publication Year: | 2016 |
| Collection: | Erasmus University Rotterdam (EUR): Figshare |
| Subject Terms: | No keyword |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| Language: | unknown |
| Relation: | 10871/21392; https://figshare.com/articles/journal_contribution/Chronic_Activation_of_2_AMPK_Induces_Obesity_and_Reduces_Cell_Function_/29718794 |
| Availability: | https://figshare.com/articles/journal_contribution/Chronic_Activation_of_2_AMPK_Induces_Obesity_and_Reduces_Cell_Function_/29718794 |
| Rights: | All rights reserved |
| Accession Number: | edsbas.5F88C657 |
| Database: | BASE |