Dietary intervention improves health metrics and life expectancy of the genetically obese Titan mouse

• Published in: Communications biology Vol. 5; no. 1; pp. 408 - 17
• Main Authors: Müller-Eigner, Annika, Sanz-Moreno, Adrián, de-Diego, Irene, Venkatasubramani, Anuroop Venkateswaran, Langhammer, Martina, Gerlini, Raffaele, Rathkolb, Birgit, Aguilar-Pimentel, Antonio, Klein-Rodewald, Tanja, Calzada-Wack, Julia, Becker, Lore, Palma-Vera, Sergio, Gille, Benedikt, Forne, Ignasi, Imhof, Axel, Meng, Chen, Ludwig, Christina, Koch, Franziska, Heiker, John T., Kuhla, Angela, Caton, Vanessa, Brenmoehl, Julia, Reyer, Henry, Schoen, Jennifer, Fuchs, Helmut, Gailus-Durner, Valerie, Hoeflich, Andreas, de Angelis, Martin Hrabe, Peleg, Shahaf
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 38/23; 38/39; 38/77; 631/337; 631/443; 631/45; 82/58; Animal models; Animals; Biology; Biomedical and Life Sciences; Body mass; Inbreeding; Life Expectancy; Life Sciences; Life span; Metabolism; Mice; Mice, Inbred Strains; Mice, Obese; Obesity; Obesity - genetics; Obesity - metabolism; Phenotype; Phenotypes; Proteomes; Quality Indicators, Health Care; Transcriptomes; Translation
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03339-3

Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The non-inbred mouse ( Mus musculus ) line Titan, also known as DU6, is one of the world’s longest selection experiments for high body mass and was previously described as a model for metabolic healthy (benign) obesity. The present study further characterizes the geno- and phenotypes of this non-inbred mouse line and tests its suitability as an interventional obesity model. In contrast to previous findings, our data suggest 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 also show modifications in the liver transcriptome, proteome, and epigenome linked to metabolic (dys)regulations. Importantly, 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. This study further characterizes the non-inbred Titan (also known as DU6) mouse line, which could be a useful model for obesity research.