|
| Status |
Public on May 03, 2016 |
| Title |
Chronic Activation of γ2 AMPK Induces Obesity and Reduces Beta Cell Function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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 signalling-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 can have adverse metabolic consequences with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease.
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| |
|
| Overall design |
Transcriptomic profiling of the hypothalamic arcuate nucleus from AMPK γ2 R299Q knock-in mice
|
| |
|
| Contributor(s) |
Lam BY, Yavari A, Petkevicius K, Ma MK, Yeo GS, Ashrafian H |
| Citation(s) |
27133129 |
| |
| Submission date |
Sep 25, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Brian Yee Hong Lam |
| E-mail(s) |
yhbl2@cam.ac.uk
|
| Organization name |
University of Cambridge
|
| Department |
Metabolic Research Laboratories
|
| Street address |
Box 289 Addenbookes Hospital, Hills Road
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0QQ |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA296960 |
| SRA |
SRP064190 |
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