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Rohm, M. ; Schäfer, M ; Laurent, V. ; Ekim Üstünel, B. ; Niopek, K. ; Algire, C. ; Hautzinger, O. ; Sijmonsma, T.P. ; Zota, A. ; Medrikova, D. ; Pellegata, N.S. ; Rydén, M.* ; Kulyte, A.* ; Dahlman, I.* ; Arner, P.* ; Petrovic, N.* ; Cannon, B.* ; Amri, E.Z.* ; Kemp, B.E.* ; Steinberg, G.R.* ; Janovska, P.* ; Kopecky, J.* ; Wolfrum, C.* ; Blüher, M.* ; Berriel Diaz, M. ; Herzig, S.

An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice.

J. Nat. Med. 22, 1120-1130 (2016)
Postprint DOI PMC
Open Access Green
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Whole-body Lipolysis; Adipocyte Lipolysis; Energy Homeostasis; Pancreatic-cancer; Lipid Homeostasis; Cell-death; Metabolism; Mechanism; Aicar; Obesity
ISSN (print) / ISBN 1340-3443
e-ISSN 1861-0293
Journal Journal of natural medicines
Quellenangaben Volume: 22, Issue: 10, Pages: 1120-1130 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Tokyo [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)