An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice.
Identifieur interne : 002384 ( Main/Exploration ); précédent : 002383; suivant : 002385An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice.
Auteurs : Maria Rohm [Allemagne] ; Michaela Sch Fer [Allemagne] ; Victor Laurent [Allemagne] ; Bilgen Ekim Üstünel [Allemagne] ; Katharina Niopek [Allemagne] ; Carolyn Algire [Allemagne] ; Oksana Hautzinger [Allemagne] ; Tjeerd P. Sijmonsma [Allemagne] ; Annika Zota [Allemagne] ; Dasa Medrikova [Allemagne] ; Natalia S. Pellegata [Allemagne] ; Mikael Ryden [Suède] ; Agné Kulyte [Suède] ; Ingrid Dahlman [Suède] ; Peter Arner [Suède] ; Natasa Petrovic [Suède] ; Barbara Cannon [Suède] ; Ez-Zoubir Amri [France] ; Bruce E. Kemp [Australie] ; Gregory R. Steinberg [Canada] ; Petra Janovska [République tchèque] ; Jan Kopecky [République tchèque] ; Christian Wolfrum [Suisse] ; Matthias Blüher [Allemagne] ; Mauricio Berriel Diaz [Allemagne] ; Stephan Herzig [Allemagne]Source :
- Nature medicine [ 1546-170X ] ; 2016.
Descripteurs français
- KwdFr :
- AMP-Activated Protein Kinases (métabolisme), AMP-Activated Protein Kinases (pharmacologie), Adipocytes blancs (), Adipocytes blancs (métabolisme), Animaux, Cachexie (métabolisme), Cachexie (étiologie), Cellules cultivées, Fragments peptidiques (pharmacologie), Lipogenèse (), Lipolyse (), Métabolisme des lipides (), Protéine-1 de découplage (), Protéine-1 de découplage (métabolisme), Protéines régulatrices de l'apoptose (), Protéines régulatrices de l'apoptose (métabolisme), Souris, Techniques in vitro, Thermogenèse (), Tissu adipeux blanc (), Tissu adipeux blanc (métabolisme), Tumeurs (), Tumeurs (métabolisme).
- MESH :
- métabolisme : AMP-Activated Protein Kinases, Adipocytes blancs, Cachexie, Protéine-1 de découplage, Protéines régulatrices de l'apoptose, Tissu adipeux blanc, Tumeurs.
- pharmacologie : AMP-Activated Protein Kinases, Fragments peptidiques.
- étiologie : Cachexie.
- Adipocytes blancs, Animaux, Cellules cultivées, Lipogenèse, Lipolyse, Métabolisme des lipides, Protéine-1 de découplage, Protéines régulatrices de l'apoptose, Souris, Techniques in vitro, Thermogenèse, Tissu adipeux blanc, Tumeurs.
English descriptors
- KwdEn :
- AMP-Activated Protein Kinases (metabolism), AMP-Activated Protein Kinases (pharmacology), Adipocytes, White (drug effects), Adipocytes, White (metabolism), Adipose Tissue, White (drug effects), Adipose Tissue, White (metabolism), Animals, Apoptosis Regulatory Proteins (drug effects), Apoptosis Regulatory Proteins (metabolism), Cachexia (etiology), Cachexia (metabolism), Cells, Cultured, In Vitro Techniques, Lipid Metabolism (drug effects), Lipogenesis (drug effects), Lipolysis (drug effects), Mice, Neoplasms (complications), Neoplasms (metabolism), Peptide Fragments (pharmacology), Thermogenesis (drug effects), Uncoupling Protein 1 (drug effects), Uncoupling Protein 1 (metabolism).
- MESH :
- chemical , drug effects : Apoptosis Regulatory Proteins, Uncoupling Protein 1.
- chemical , metabolism : AMP-Activated Protein Kinases, Apoptosis Regulatory Proteins, Uncoupling Protein 1.
- chemical , pharmacology : AMP-Activated Protein Kinases, Peptide Fragments.
- complications : Neoplasms.
- drug effects : Adipocytes, White, Adipose Tissue, White, Lipid Metabolism, Lipogenesis, Lipolysis, Thermogenesis.
- etiology : Cachexia.
- metabolism : Adipocytes, White, Adipose Tissue, White, Cachexia, Neoplasms.
- Animals, Cells, Cultured, In Vitro Techniques, Mice.
Abstract
Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.
DOI: 10.1038/nm.4171
PubMed: 27571348
Affiliations:
- Allemagne, Australie, Canada, France, République tchèque, Suisse, Suède
- Bohême centrale, District de Leipzig, Ontario, Provence-Alpes-Côte d'Azur, Saxe (Land), Svealand, Victoria (État)
- Hamilton (Ontario), Leipzig, Melbourne, Nice, Prague, Stockholm
- Université McMaster, Université de Melbourne, Université de Stockholm
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Le document en format XML
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Kemp</name><affiliation wicri:level="4"><nlm:affiliation>St Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>St Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R" last="Steinberg">Gregory R. Steinberg</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Janovska, Petra" sort="Janovska, Petra" uniqKey="Janovska P" first="Petra" last="Janovska">Petra Janovska</name><affiliation wicri:level="3"><nlm:affiliation>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Kopecky, Jan" sort="Kopecky, Jan" uniqKey="Kopecky J" first="Jan" last="Kopecky">Jan Kopecky</name><affiliation wicri:level="3"><nlm:affiliation>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Wolfrum, Christian" sort="Wolfrum, Christian" uniqKey="Wolfrum C" first="Christian" last="Wolfrum">Christian Wolfrum</name><affiliation wicri:level="1"><nlm:affiliation>Swiss Federal Institute of Technology, Institute of Food Nutrition and Health, Schwerzenbach, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Swiss Federal Institute of Technology, Institute of Food Nutrition and Health, Schwerzenbach</wicri:regionArea><wicri:noRegion>Schwerzenbach</wicri:noRegion></affiliation></author><author><name sortKey="Bluher, Matthias" sort="Bluher, Matthias" uniqKey="Bluher M" first="Matthias" last="Blüher">Matthias Blüher</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine, University of Leipzig, Leipzig, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine, University of Leipzig, Leipzig</wicri:regionArea><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Leipzig</region><settlement type="city">Leipzig</settlement></placeName></affiliation></author><author><name sortKey="Berriel Diaz, Mauricio" sort="Berriel Diaz, Mauricio" uniqKey="Berriel Diaz M" first="Mauricio" last="Berriel Diaz">Mauricio Berriel Diaz</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Herzig, Stephan" sort="Herzig, Stephan" uniqKey="Herzig S" first="Stephan" last="Herzig">Stephan Herzig</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27571348</idno><idno type="pmid">27571348</idno><idno type="doi">10.1038/nm.4171</idno><idno type="wicri:Area/PubMed/Corpus">001743</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001743</idno><idno type="wicri:Area/PubMed/Curation">001720</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001720</idno><idno type="wicri:Area/PubMed/Checkpoint">001720</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001720</idno><idno 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Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Sch Fer, Michaela" sort="Sch Fer, Michaela" uniqKey="Sch Fer M" first="Michaela" last="Sch Fer">Michaela Sch Fer</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Laurent, Victor" sort="Laurent, Victor" uniqKey="Laurent V" first="Victor" last="Laurent">Victor Laurent</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Ustunel, Bilgen Ekim" sort="Ustunel, Bilgen Ekim" uniqKey="Ustunel B" first="Bilgen Ekim" last="Üstünel">Bilgen Ekim Üstünel</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Niopek, Katharina" sort="Niopek, Katharina" uniqKey="Niopek K" first="Katharina" last="Niopek">Katharina Niopek</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Algire, Carolyn" sort="Algire, Carolyn" uniqKey="Algire C" first="Carolyn" last="Algire">Carolyn Algire</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Hautzinger, Oksana" sort="Hautzinger, Oksana" uniqKey="Hautzinger O" first="Oksana" last="Hautzinger">Oksana Hautzinger</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Sijmonsma, Tjeerd P" sort="Sijmonsma, Tjeerd P" uniqKey="Sijmonsma T" first="Tjeerd P" last="Sijmonsma">Tjeerd P. Sijmonsma</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Zota, Annika" sort="Zota, Annika" uniqKey="Zota A" first="Annika" last="Zota">Annika Zota</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Medrikova, Dasa" sort="Medrikova, Dasa" uniqKey="Medrikova D" first="Dasa" last="Medrikova">Dasa Medrikova</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Pellegata, Natalia S" sort="Pellegata, Natalia S" uniqKey="Pellegata N" first="Natalia S" last="Pellegata">Natalia S. Pellegata</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Ryden, Mikael" sort="Ryden, Mikael" uniqKey="Ryden M" first="Mikael" last="Ryden">Mikael Ryden</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Kulyte, Agne" sort="Kulyte, Agne" uniqKey="Kulyte A" first="Agné" last="Kulyte">Agné Kulyte</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Dahlman, Ingrid" sort="Dahlman, Ingrid" uniqKey="Dahlman I" first="Ingrid" last="Dahlman">Ingrid Dahlman</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Arner, Peter" sort="Arner, Peter" uniqKey="Arner P" first="Peter" last="Arner">Peter Arner</name><affiliation wicri:level="3"><nlm:affiliation>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Lipid Laboratory, Department of Medicine, Karolinska Institute, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Petrovic, Natasa" sort="Petrovic, Natasa" uniqKey="Petrovic N" first="Natasa" last="Petrovic">Natasa Petrovic</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region><settlement type="city">Stockholm</settlement></placeName><orgName type="university">Université de Stockholm</orgName></affiliation></author><author><name sortKey="Cannon, Barbara" sort="Cannon, Barbara" uniqKey="Cannon B" first="Barbara" last="Cannon">Barbara Cannon</name><affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region><settlement type="city">Stockholm</settlement></placeName><orgName type="university">Université de Stockholm</orgName></affiliation></author><author><name sortKey="Amri, Ez Zoubir" sort="Amri, Ez Zoubir" uniqKey="Amri E" first="Ez-Zoubir" last="Amri">Ez-Zoubir Amri</name><affiliation wicri:level="3"><nlm:affiliation>Université Côte d'Azur, Nice, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Côte d'Azur, Nice</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Kemp, Bruce E" sort="Kemp, Bruce E" uniqKey="Kemp B" first="Bruce E" last="Kemp">Bruce E. Kemp</name><affiliation wicri:level="4"><nlm:affiliation>St Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>St Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R" last="Steinberg">Gregory R. Steinberg</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Janovska, Petra" sort="Janovska, Petra" uniqKey="Janovska P" first="Petra" last="Janovska">Petra Janovska</name><affiliation wicri:level="3"><nlm:affiliation>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Kopecky, Jan" sort="Kopecky, Jan" uniqKey="Kopecky J" first="Jan" last="Kopecky">Jan Kopecky</name><affiliation wicri:level="3"><nlm:affiliation>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Wolfrum, Christian" sort="Wolfrum, Christian" uniqKey="Wolfrum C" first="Christian" last="Wolfrum">Christian Wolfrum</name><affiliation wicri:level="1"><nlm:affiliation>Swiss Federal Institute of Technology, Institute of Food Nutrition and Health, Schwerzenbach, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Swiss Federal Institute of Technology, Institute of Food Nutrition and Health, Schwerzenbach</wicri:regionArea><wicri:noRegion>Schwerzenbach</wicri:noRegion></affiliation></author><author><name sortKey="Bluher, Matthias" sort="Bluher, Matthias" uniqKey="Bluher M" first="Matthias" last="Blüher">Matthias Blüher</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medicine, University of Leipzig, Leipzig, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medicine, University of Leipzig, Leipzig</wicri:regionArea><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Leipzig</region><settlement type="city">Leipzig</settlement></placeName></affiliation></author><author><name sortKey="Berriel Diaz, Mauricio" sort="Berriel Diaz, Mauricio" uniqKey="Berriel Diaz M" first="Mauricio" last="Berriel Diaz">Mauricio Berriel Diaz</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Herzig, Stephan" sort="Herzig, Stephan" uniqKey="Herzig S" first="Stephan" last="Herzig">Stephan Herzig</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature medicine</title><idno type="eISSN">1546-170X</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP-Activated Protein Kinases (metabolism)</term><term>AMP-Activated Protein Kinases (pharmacology)</term><term>Adipocytes, White (drug effects)</term><term>Adipocytes, White (metabolism)</term><term>Adipose Tissue, White (drug effects)</term><term>Adipose Tissue, White (metabolism)</term><term>Animals</term><term>Apoptosis Regulatory Proteins (drug effects)</term><term>Apoptosis Regulatory Proteins (metabolism)</term><term>Cachexia (etiology)</term><term>Cachexia (metabolism)</term><term>Cells, Cultured</term><term>In Vitro Techniques</term><term>Lipid Metabolism (drug effects)</term><term>Lipogenesis (drug effects)</term><term>Lipolysis (drug effects)</term><term>Mice</term><term>Neoplasms (complications)</term><term>Neoplasms (metabolism)</term><term>Peptide Fragments (pharmacology)</term><term>Thermogenesis (drug effects)</term><term>Uncoupling Protein 1 (drug effects)</term><term>Uncoupling Protein 1 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>AMP-Activated Protein Kinases (métabolisme)</term><term>AMP-Activated Protein Kinases (pharmacologie)</term><term>Adipocytes blancs ()</term><term>Adipocytes blancs (métabolisme)</term><term>Animaux</term><term>Cachexie (métabolisme)</term><term>Cachexie (étiologie)</term><term>Cellules cultivées</term><term>Fragments peptidiques (pharmacologie)</term><term>Lipogenèse ()</term><term>Lipolyse ()</term><term>Métabolisme des lipides ()</term><term>Protéine-1 de découplage ()</term><term>Protéine-1 de découplage (métabolisme)</term><term>Protéines régulatrices de l'apoptose ()</term><term>Protéines régulatrices de l'apoptose (métabolisme)</term><term>Souris</term><term>Techniques in vitro</term><term>Thermogenèse ()</term><term>Tissu adipeux blanc ()</term><term>Tissu adipeux blanc (métabolisme)</term><term>Tumeurs ()</term><term>Tumeurs (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Apoptosis Regulatory Proteins</term><term>Uncoupling Protein 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term><term>Apoptosis Regulatory Proteins</term><term>Uncoupling Protein 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>AMP-Activated Protein Kinases</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Neoplasms</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Adipocytes, White</term><term>Adipose Tissue, White</term><term>Lipid Metabolism</term><term>Lipogenesis</term><term>Lipolysis</term><term>Thermogenesis</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Cachexia</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adipocytes, White</term><term>Adipose Tissue, White</term><term>Cachexia</term><term>Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term><term>Adipocytes blancs</term><term>Cachexie</term><term>Protéine-1 de découplage</term><term>Protéines régulatrices de l'apoptose</term><term>Tissu adipeux blanc</term><term>Tumeurs</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>AMP-Activated Protein Kinases</term><term>Fragments peptidiques</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Cachexie</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cells, Cultured</term><term>In Vitro Techniques</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adipocytes blancs</term><term>Animaux</term><term>Cellules cultivées</term><term>Lipogenèse</term><term>Lipolyse</term><term>Métabolisme des lipides</term><term>Protéine-1 de découplage</term><term>Protéines régulatrices de l'apoptose</term><term>Souris</term><term>Techniques in vitro</term><term>Thermogenèse</term><term>Tissu adipeux blanc</term><term>Tumeurs</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>France</li><li>République tchèque</li><li>Suisse</li><li>Suède</li></country><region><li>Bohême centrale</li><li>District de Leipzig</li><li>Ontario</li><li>Provence-Alpes-Côte d'Azur</li><li>Saxe (Land)</li><li>Svealand</li><li>Victoria (État)</li></region><settlement><li>Hamilton (Ontario)</li><li>Leipzig</li><li>Melbourne</li><li>Nice</li><li>Prague</li><li>Stockholm</li></settlement><orgName><li>Université McMaster</li><li>Université de Melbourne</li><li>Université de Stockholm</li></orgName></list><tree><country name="Allemagne"><noRegion><name sortKey="Rohm, Maria" sort="Rohm, Maria" uniqKey="Rohm M" first="Maria" last="Rohm">Maria Rohm</name></noRegion><name sortKey="Algire, Carolyn" sort="Algire, Carolyn" uniqKey="Algire C" first="Carolyn" last="Algire">Carolyn Algire</name><name sortKey="Berriel Diaz, Mauricio" sort="Berriel Diaz, Mauricio" uniqKey="Berriel Diaz M" first="Mauricio" last="Berriel Diaz">Mauricio Berriel Diaz</name><name sortKey="Bluher, Matthias" sort="Bluher, Matthias" uniqKey="Bluher M" first="Matthias" last="Blüher">Matthias Blüher</name><name sortKey="Hautzinger, Oksana" sort="Hautzinger, Oksana" uniqKey="Hautzinger O" first="Oksana" last="Hautzinger">Oksana Hautzinger</name><name sortKey="Herzig, Stephan" sort="Herzig, Stephan" uniqKey="Herzig S" first="Stephan" last="Herzig">Stephan Herzig</name><name sortKey="Laurent, Victor" sort="Laurent, Victor" uniqKey="Laurent V" first="Victor" last="Laurent">Victor Laurent</name><name sortKey="Medrikova, Dasa" sort="Medrikova, Dasa" uniqKey="Medrikova D" first="Dasa" last="Medrikova">Dasa Medrikova</name><name sortKey="Niopek, Katharina" sort="Niopek, Katharina" uniqKey="Niopek K" first="Katharina" last="Niopek">Katharina Niopek</name><name sortKey="Pellegata, Natalia S" sort="Pellegata, Natalia S" uniqKey="Pellegata N" first="Natalia S" last="Pellegata">Natalia S. Pellegata</name><name sortKey="Sch Fer, Michaela" sort="Sch Fer, Michaela" uniqKey="Sch Fer M" first="Michaela" last="Sch Fer">Michaela Sch Fer</name><name sortKey="Sijmonsma, Tjeerd P" sort="Sijmonsma, Tjeerd P" uniqKey="Sijmonsma T" first="Tjeerd P" last="Sijmonsma">Tjeerd P. Sijmonsma</name><name sortKey="Ustunel, Bilgen Ekim" sort="Ustunel, Bilgen Ekim" uniqKey="Ustunel B" first="Bilgen Ekim" last="Üstünel">Bilgen Ekim Üstünel</name><name sortKey="Zota, Annika" sort="Zota, Annika" uniqKey="Zota A" first="Annika" last="Zota">Annika Zota</name></country><country name="Suède"><region name="Svealand"><name sortKey="Ryden, Mikael" sort="Ryden, Mikael" uniqKey="Ryden M" first="Mikael" last="Ryden">Mikael Ryden</name></region><name sortKey="Arner, Peter" sort="Arner, Peter" uniqKey="Arner P" first="Peter" last="Arner">Peter Arner</name><name sortKey="Cannon, Barbara" sort="Cannon, Barbara" uniqKey="Cannon B" first="Barbara" last="Cannon">Barbara Cannon</name><name sortKey="Dahlman, Ingrid" sort="Dahlman, Ingrid" uniqKey="Dahlman I" first="Ingrid" last="Dahlman">Ingrid Dahlman</name><name sortKey="Kulyte, Agne" sort="Kulyte, Agne" uniqKey="Kulyte A" first="Agné" last="Kulyte">Agné Kulyte</name><name sortKey="Petrovic, Natasa" sort="Petrovic, Natasa" uniqKey="Petrovic N" first="Natasa" last="Petrovic">Natasa Petrovic</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Amri, Ez Zoubir" sort="Amri, Ez Zoubir" uniqKey="Amri E" first="Ez-Zoubir" last="Amri">Ez-Zoubir Amri</name></region></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Kemp, Bruce E" sort="Kemp, Bruce E" uniqKey="Kemp B" first="Bruce E" last="Kemp">Bruce E. Kemp</name></region></country><country name="Canada"><region name="Ontario"><name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R" last="Steinberg">Gregory R. Steinberg</name></region></country><country name="République tchèque"><region name="Bohême centrale"><name sortKey="Janovska, Petra" sort="Janovska, Petra" uniqKey="Janovska P" first="Petra" last="Janovska">Petra Janovska</name></region><name sortKey="Kopecky, Jan" sort="Kopecky, Jan" uniqKey="Kopecky J" first="Jan" last="Kopecky">Jan Kopecky</name></country><country name="Suisse"><noRegion><name sortKey="Wolfrum, Christian" sort="Wolfrum, Christian" uniqKey="Wolfrum C" first="Christian" last="Wolfrum">Christian Wolfrum</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
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