PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Castoldi, F.* ; Hyvönen, M.T.* ; Durand, S.* ; Aprahamian, F.* ; Sauvat, A.* ; Malik, S.A.* ; Baracco, E.E.* ; Vacchelli, E.* ; Opolon, P.* ; Signolle, N.* ; Lefevre, D.* ; Bossut, N.* ; Eisenberg, T.* ; Dammbrueck, C.* ; Pendl, T.* ; Kremer, M.* ; Lachkar, S.* ; Einer, C. ; Michalke, B. ; Zischka, H. ; Madeo, F.* ; Keinänen, T.A.* ; Maiuri, M.C.* ; Pietrocola, F.*

Chemical activation of SAT1 corrects diet-induced metabolic syndrome.

Cell Death Differ. 27, 2904-2920 (2020)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Green
The pharmacological targeting of polyamine metabolism is currently under the spotlight for its potential in the prevention and treatment of several age-associated disorders. Here, we report the finding that triethylenetetramine dihydrochloride (TETA), a copper-chelator agent that can be safely administered to patients for the long-term treatment of Wilson disease, exerts therapeutic benefits in animals challenged with hypercaloric dietary regimens. TETA reduced obesity induced by high-fat diet, excessive sucrose intake, or leptin deficiency, as it reduced glucose intolerance and hepatosteatosis, but induced autophagy. Mechanistically, these effects did not involve the depletion of copper from plasma or internal organs. Rather, the TETA effects relied on the activation of an energy-consuming polyamine catabolism, secondary to the stabilization of spermidine/spermine N1-acetyltransferase-1 (SAT1) by TETA, resulting in enhanced enzymatic activity of SAT. All the positive effects of TETA on high-fat diet-induced metabolic syndrome were lost in SAT1-deficient mice. Altogether, these results suggest novel health-promoting effects of TETA that might be taken advantage of for the prevention or treatment of obesity.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
10.717
2.092
10
16
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Caloric Restriction Mimetics; Life-span; Spermidine; Autophagy; Disease; Spermidine/spermine-n-1-acetyltransferase; Triethylenetetramine; Derivatives; Mice; Mass
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 1350-9047
e-ISSN 1476-5403
Journal Cell Death and Differentiation
Quellenangaben Volume: 27, Issue: 10, Pages: 2904-2920 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)
Research Unit BioGeoChemistry and Analytics (BGC)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30202 - Environmental Health
Research field(s) Enabling and Novel Technologies
Environmental Sciences
PSP Element(s) G-505200-003
G-504800-002
DOI 10.1038/s41418-020-0550-z
WOS ID WOS:000530779800001
Scopus ID 85085120090
PubMed ID 32376874
Erfassungsdatum 2020-05-14
[➜Report correction]