ArticleCell metabolism2016
Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.
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Article in Cell metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71citing papers in PubMed
13.5field-weighted citation impact, top 1% of its field
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Who cites it
71 citing papers in PubMed, 109 citations in OpenAlex.
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- Comparative analysis of muscle pathologies and metabolic signaling in mouse models of mitochondrial dysfunction.Scientific reports · 2026Article
- Physiological interplay among obesity, male fertility, and aryl hydrocarbon receptor in human and mice: A mini review.Open veterinary journal · 2026Review
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders.Metabolism open · 2025Review
- Involvement of NRF2 and AMPK signaling in aging and progeria: a digest.Redox biology · 2025Review
- Impact of Acute Endurance Exercise on Alternative Splicing in Skeletal Muscle.FASEB bioAdvances · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Impact of Acute Endurance Exercise on Alternative Splicing in Skeletal Muscle.bioRxiv : the preprint server for biology · 2025Article
- Obesity: pathophysiology and therapeutic interventions.Molecular biomedicine · 2025Review
- SF1-specific deletion of the energy sensor AMPKγ2 induces obesity.Molecular metabolism · 2025Article
- AMPK phosphosite profiling by label-free mass spectrometry reveals a multitude of mTORC1-regulated substrates.npj metabolic health and disease · 2025Article
- Hypothalamic GABAergic neurons: their roles in health and metabolic diseases.Frontiers in endocrinology · 2025Review
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- New developments in AMPK and mTORC1 cross-talk.Essays in biochemistry · 2024Review
- AMPK as a mediator of tissue preservation: time for a shift in dogma?Nature reviews. Endocrinology · 2024Review
- A brainstem to hypothalamic arcuate nucleus GABAergic circuit drives feeding.Current biology : CB · 2024Article
- Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures.Psychiatry research · 2024Article
- Refeeding-associated AMPKNature aging · 2023Article
- NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development.Nature communications · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
54 authors at 16 institutions in 4 countries.
Arash YavariExperimental Therapeutics, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. Electronic address: arash.yavari@well.ox.ac.uk.
Claire J StockerThe Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
Sahar GhaffariDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Edward T WargentThe Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
Violetta SteeplesDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Gabor CzibikDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Katalin PinterDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Mohamed BellahceneDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Angela WoodsCellular Stress Group, MRC Clinical Sciences Centre, Imperial College London, London SW7 2AZ, UK.
Pablo B Martínez de MorentinRowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Céline CansellRowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Brian Y H LamUniversity of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
André ChusterPos Graduação Ciências Médicas, Faculdade Ciências Médicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG 31270-901, Brazil.
Kasparas PetkeviciusUniversity of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Marie-Sophie Nguyen-TuCell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
Aida Martinez-SanchezCell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
Timothy J PullenCell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
Peter L OliverMRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, UK.
Alexander StockenhuberDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Chinh NguyenDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Merzaka LazdamDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
Jacqueline F O'DowdThe Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
Parvathy HarikumarThe Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
Mónika TóthDepartment of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
Craig BeallCardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK.
Theodosios KyriakouDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Julia ParnisDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Dhruv SarmaDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
George KatritsisDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Diana D J WortmannDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Andrew R HarperDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Laurence A BrownNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Robin WillowsCellular Stress Group, MRC Clinical Sciences Centre, Imperial College London, London SW7 2AZ, UK.
Silvia GandraPos Graduação Ciências Médicas, Faculdade Ciências Médicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG 31270-901, Brazil.
Victor PoncioUniversidade Estadual de Campinas, Campinas-SP 13083-970, Brazil.
Márcio J de Oliveira FigueiredoUniversidade Estadual de Campinas, Campinas-SP 13083-970, Brazil.
Nathan R QiDepartment of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Stuart N PeirsonNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Rory J McCrimmonCardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK.
Balázs GerebenDepartment of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
László TretterDepartment of Medical Biochemistry, Semmelweis University, Budapest 1085, Hungary; MTA-SE Laboratory for Neurobiochemistry, Semmelweis University, Budapest 1085, Hungary.
Csaba FeketeDepartment of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary; Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Charles RedwoodDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Giles S H YeoUniversity of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Lora K HeislerRowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Guy A RutterCell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London SW7 2AZ, UK.
Mark A SmithMetabolic Signalling Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, UK.
Dominic J WithersMetabolic Signalling Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, UK.
David CarlingCellular Stress Group, MRC Clinical Sciences Centre, Imperial College London, London SW7 2AZ, UK.
Eduardo B SternickPos Graduação Ciências Médicas, Faculdade Ciências Médicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG 31270-901, Brazil.
Jonathan R S ArchThe Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
Michael A CawthorneThe Buckingham Institute for Translational Medicine, University of Buckingham, Buckingham MK18 1EG, UK.
Hugh WatkinsDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Houman AshrafianExperimental Therapeutics, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Experimental Therapeutics, Clinical Science Group, New Medicines, UCB Pharma S.A., Slough, Berkshire SL1 3WE, UK. Electronic address: houman.ashrafian@cardiov.ox.ac.uk.
University of Oxford · GBImperial College London · GBCentre for Human Genetics · GBUniversity of Buckingham · GBUniversidade Federal de Minas Gerais · BRUniversity of Aberdeen · GBUniversidade Estadual de Campinas (UNICAMP) · BRUniversity of Dundee · GBWellcome Trust · GBHungarian Academy of Sciences · HUHUN-REN Institute of Experimental Medicine · HUNuffield Orthopaedic Centre · GBSemmelweis University · HUTufts Medical Center · USUniversity of Michigan · USWellcome/MRC Institute of Metabolic Science · GB
Funding
PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MPilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joyce Lee · 2010 to 2026
$20.3MMichigan Mouse Metabolic Phenotyping CenterU2CDK110768 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELIAS, CAROL FUZETI · 2016 to 2021
$6.2MBritish Heart Foundation RG/12/16/29939Diabetes UK 13/0004647Medical Research Council MC_U120027537Medical Research Council MC_U120097114Medical Research Council MR/K001981/1Medical Research Council MR/K019023/1NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK089503NIDDK NIH HHS P60 DK020572NIDDK NIH HHS U2C DK110768
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.
Indexed as
AdiposityAdultAgingAgouti-Related ProteinAMP-Activated Protein KinasesAnimalsArcuate Nucleus of HypothalamusEnergy MetabolismEnzyme ActivationFeeding BehaviorFemaleHeterozygoteHumansHyperphagiaHypothalamusInsulinAgouti-Related ProteinAMP-Activated Protein KinasesInsulinReceptors, Ghrelin
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