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An AMP-activated pr...
An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-08-29
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Springer Science and Business Media LLC,2016
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-136107
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-136107URI
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https://doi.org/10.1038/nm.4171DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:134371900URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
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Schäfer, Michaela
(author)
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Laurent, Victor
(author)
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Üstünel, Bilgen Ekim
(author)
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Niopek, Katharina
(author)
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Algire, Carolyn
(author)
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Hautzinger, Oksana
(author)
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Sijmonsma, Tjeerd P.
(author)
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Zota, Annika
(author)
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Medrikova, Dasa
(author)
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Pellegata, Natalia S.
(author)
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Ryden, MikaelKarolinska Institutet
(author)
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Kulyte, AgnéKarolinska Institutet
(author)
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Dahlman, IngridKarolinska Institutet
(author)
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Arner, PeterKarolinska Institutet
(author)
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Petrovic, NatasaStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)npetr
(author)
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Cannon, BarbaraStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)canno
(author)
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Amri, Ez-Zoubir
(author)
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Kemp, Bruce E.
(author)
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Steinberg, Gregory R.
(author)
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Janovska, Petra
(author)
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Kopecky, Jan
(author)
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Wolfrum, Christian
(author)
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Blüher, Matthias
(author)
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Diaz, Mauricio Berriel
(author)
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Herzig, Stephan
(author)
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Karolinska InstitutetInstitutionen för molekylär biovetenskap, Wenner-Grens institut
(creator_code:org_t)
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In:Nature Medicine: Springer Science and Business Media LLC22:10, s. 1120-11301078-89561546-170X
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Rohm, Maria
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Schäfer, Michael ...
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Laurent, Victor
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Üstünel, Bilgen ...
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Niopek, Katharin ...
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Algire, Carolyn
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Hautzinger, Oksa ...
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Sijmonsma, Tjeer ...
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Zota, Annika
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Medrikova, Dasa
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Pellegata, Natal ...
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Ryden, Mikael
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Kulyte, Agné
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Dahlman, Ingrid
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Arner, Peter
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Petrovic, Natasa
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Cannon, Barbara
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Amri, Ez-Zoubir
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Kemp, Bruce E.
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Steinberg, Grego ...
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Janovska, Petra
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Kopecky, Jan
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Wolfrum, Christi ...
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Blüher, Matthias
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Diaz, Mauricio B ...
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Herzig, Stephan
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NATURAL SCIENCES
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MEDICAL AND HEAL ...
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Nature Medicine
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Stockholm University
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Karolinska Institutet