Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function
| Autor: | Pullen, Timothy J |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Heterozygote Insulin/metabolism Mutation/genetics Insulin-Secreting Cells/enzymology AMP-Activated Protein Kinases/metabolism Neurons/metabolism Receptors Ghrelin/metabolism Agouti-Related Protein/metabolism Oxidative Phosphorylation Up-Regulation/genetics Mice Aging/pathology Mitochondria/metabolism Animals Humans Ribosomes/metabolism Energy Metabolism/genetics Hypothalamus/metabolism Feeding Behavior Transcriptome/genetics Enzyme Activation Obesity/blood Hyperphagia/complications Adiposity/genetics Signal Transduction/genetics Female Arcuate Nucleus of Hypothalamus/metabolism |
| Zdroj: | Pullen, T J 2016, ' Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function ', CELL METABOLISM, vol. 23, no. 5, pp. 821-836 . https://doi.org/10.1016/j.cmet.2016.04.003 |
| DOI: | 10.1016/j.cmet.2016.04.003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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