An AMP-activated protein kinase–stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00466490" target="_blank" >RIV/67985823:_____/16:00466490 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1038/nm.4171" target="_blank" >http://dx.doi.org/10.1038/nm.4171</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/nm.4171" target="_blank" >10.1038/nm.4171</a>
Alternative languages
Result language
angličtina
Original language name
An AMP-activated protein kinase–stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FB - Endocrinology, diabetology, metabolism, nutrition
OECD FORD branch
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Result continuities
Project
<a href="/en/project/7E12073" target="_blank" >7E12073: DIABAT - Recruitment and activation of brown adipocytes as preventive and curative therapy for type 2 diabetes</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Medicine
ISSN
1078-8956
e-ISSN
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Volume of the periodical
22
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
1120-1130
UT code for WoS article
000384872500015
EID of the result in the Scopus database
2-s2.0-84984622665