Nature medicine, 2016-10, Vol.22 (10), p.1120-1130
- Rohm, Maria
- Schäfer, Michaela
- Laurent, Victor
- Üstünel, Bilgen Ekim
- Niopek, Katharina
- Algire, Carolyn
- Hautzinger, Oksana
- Sijmonsma, Tjeerd P
- Zota, Annika
- Medrikova, Dasa
- Pellegata, Natalia S
- Ryden, Mikael
- Kulyte, Agné
- Dahlman, Ingrid
- Arner, Peter
- Petrovic, Natasa
- Cannon, Barbara
- Amri, Ez-Zoubir
- Kemp, Bruce E
- Steinberg, Gregory R
- Janovska, Petra
- Kopecky, Jan
- Wolfrum, Christian
- Blüher, Matthias
- Berriel Diaz, Mauricio
- Herzig, Stephan
2016
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- Autor(en) / Beteiligte
- Rohm, Maria
- Schäfer, Michaela
- Laurent, Victor
- Üstünel, Bilgen Ekim
- Niopek, Katharina
- Algire, Carolyn
- Hautzinger, Oksana
- Sijmonsma, Tjeerd P
- Zota, Annika
- Medrikova, Dasa
- Pellegata, Natalia S
- Ryden, Mikael
- Kulyte, Agné
- Dahlman, Ingrid
- Arner, Peter
- Petrovic, Natasa
- Cannon, Barbara
- Amri, Ez-Zoubir
- Kemp, Bruce E
- Steinberg, Gregory R
- Janovska, Petra
- Kopecky, Jan
- Wolfrum, Christian
- Blüher, Matthias
- Berriel Diaz, Mauricio
- Herzig, Stephan
- Titel
- An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice
- Ist Teil von
- Nature medicine, 2016-10, Vol.22 (10), p.1120-1130
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1078-8956, 1546-170XeISSN: 1546-170XDOI: 10.1038/nm.4171Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_134371900
- Format
- –
- Schlagworte
- Adipocytes, Adipocytes, White - drug effects, Adipocytes, White - metabolism, Adipose tissue, Adipose Tissue, White - drug effects, Adipose Tissue, White - metabolism, Adipose tissues, AMP, AMP-activated protein kinase, AMP-Activated Protein Kinases - metabolism, AMP-Activated Protein Kinases - pharmacology, Animals, Apoptosis Regulatory Proteins - drug effects, Apoptosis Regulatory Proteins - metabolism, Cachexia, Cachexia - etiology, Cachexia - metabolism, Cancer, Cells, Cultured, Deactivation, Energy, Genetic aspects, Health aspects, Homeostasis, In Vitro Techniques, Inactivation, Kinases, Lipid Metabolism - drug effects, Lipogenesis - drug effects, Lipolysis - drug effects, Medicin och hälsovetenskap, Mice, Muscles, Neoplasms - complications, Neoplasms - metabolism, Peptide Fragments - pharmacology, Peptides, Phosphates, Preservation, Protein kinases, Proteins, Shielding, Skeletal muscle, Thermogenesis, Thermogenesis - drug effects, Tumors, Uncoupling protein 1, Uncoupling Protein 1 - drug effects, Uncoupling Protein 1 - metabolism