RT Journal Article
SR Electronic
T1 Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.11.088625
DO 10.1101/2020.05.11.088625
A1 Annika Müller-Eigner
A1 Adrián Sanz-Moreno
A1 Irene de-Diego
A1 Anuroop Venkateswaran Venkatasubramani
A1 Martina Langhammer
A1 Raffaele Gerlini
A1 Birgit Rathkolb
A1 Antonio Aguilar-Pimentel
A1 Tanja Klein-Rodewald
A1 Julia Calzada-Wack
A1 Lore Becker
A1 Sergio Palma-Vera
A1 Benedikt Gille
A1 Ignasi Forne
A1 Axel Imhof
A1 Chen Meng
A1 Christina Ludwig
A1 Franziska Koch
A1 Angela Kuhla
A1 Vanessa Caton
A1 Julia Brenmoehl
A1 Jennifer Schoen
A1 Helmut Fuchs
A1 Valerie Gailus-Durner
A1 Andreas Hoeflich
A1 Martin Hrabe de Angelis
A1 Shahaf Peleg
YR 2021
UL http://biorxiv.org/content/early/2021/06/09/2020.05.11.088625.abstract
AB Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The outbred mouse line Titan (DU6) results from the world’s longest selection experiment for high body mass and was previously described as a model for metabolic healthy (benign) obesity. The present study deeper characterized the geno- and phenotypes of this outbred mouse line and tested its suitability as an interventional obesity model. In contrast to previous findings, our data suggests that Titan mice are metabolically unhealthy obese and short-lived. Line-specific patterns of genetic invariability are in accordance with observed phenotypic traits. Titan mice show modifications in the liver transcriptome, proteome and epigenome that are linked to metabolic (dys)regulations. However, dietary intervention partially reversed the metabolic phenotype in Titan mice and significantly extended their life expectancy. Therefore, the Titan mouse line is a valuable resource for translational and interventional obesity research.Competing Interest StatementThe authors have declared no competing interest.