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.

Juvenile African catfish (Clarias gariepinus Burchell, 1822) were reared within two experiments (a research facility and a local catfish farm, E1 and E2, respectively) for 102 d each under commercial recirculating aquaculture conditions. The mixed-layer clay mineral montmorillonite–illite/muscovite (1g557) was applied as a feed additive at concentrations of 0.5% and 2.0%, which were compared with an unsupplemented control (0.0%) over 70 d. For E1, feeding was automatic at night, while E2 was fed manually during the day. The growth and physiological welfare parameters of the fish were monitored, including the mortality, skin lesions, stress responses after confinement (plasma cortisol and glucose), and additional blood parameters. Tendentially, the most efficient growth in both the experiments was observed in the 0.5% groups, which performed slightly better than the controls (E1: 0.8% and E2: 3.2%) despite a lower nutrient content (p > 0.05). In E1, the negative skewness of the leptokurtic distribution also revealed the highest number of larger-sized fish per batch. Mortality was low in all the treatment groups (E1 control/0.5%/2.0%: 3.6%/4.9%/2.9%; E2 control/0.5%: 2.6%/5.5%). After only 29 d in E1, the number of skin lesions per fish decreased significantly (p < 0.05 between each of the 0.5% and 2.0% groups, compared to the control (E1 control/0.5%/2.0%: 1.2/0.8/0.8). In both E1 and E2, the number of lesions per fish decreased even further after 70 d, significantly between the treatment groups and the control (E1 control/0.5%/2.0%: 0.9/0.4/0.5 and E2 control/0.5%: 0.6/0.3). In E1, the cortisol and glucose concentrations increased strongly in all the groups due to the induced stress, whereas this was not evident in E2 based on the different sampling procedure. The additional blood parameters (aspartate aminotransferase, glutamate dehydrogenase, urea, calcium, phosphate, total protein, leucocytes, erythrocytes, hematocrit, cholesterol, triglycerides, sodium, potassium, and chloride) revealed no significant difference between the treatment groups in either experiment, indicating no negative effects of 1g557 on the organs or metabolism of the fish. Supplementation with 0.5% 1g557 in the common commercial feeds for African catfish increases growth performance (p > 0.05), reduces size variance, and supports fish welfare under different commercial aquaculture conditions in the present study.

Wild-type murine models for aging research have lifespans of several years, which results in long experimental duration and late output. Here we explore the short-lived non-inbred Titan mouse as a mouse model to test longevity interventions. We show that Titan mice exhibit increased frailty and cellular senescence at an early age. Dietary intervention attenuates the frailty progression of Titan mice. Additionally, cyclic administration of the senolytic drug Navitoclax at early age increases the lifespan and reduces cellular senescence. Our data suggests that Titan mice can serve as a cost-effective and timely model for longevity interventions in mammals.

Butyrate has been proposed as a drug therapy by acting as a KDAC inhibitor and elevating protein acetylation, in particular on histones. Nonetheless, recent studies suggest that tissues such as the gut can utilize butyrate as a metabolite. We have previously shown that the addition of butyrate induces a rapid increase of oxygen consumption in whole Drosophila melanogaster heads. Here we show that while head oxygen consumption is increased by the addition of butyrate, no apparent changes are observed on the proteome and acetylome. Instead, we show that butyrate is metabolized and incorporated into the tricarboxylic acid cycle (TCA) cycle. Collectivity our data supports the notion that the therapeutic benefits of acute butyrate treatment may be also mediated by improving metabolic rates, rather than solely targeting the epigenome or acetylome.