The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice.

BACKGROUND: Metabolic disorders are commonly investigated using knockout and transgenic mouse models on the C57BL/6N genetic background due to its genetic susceptibility to the deleterious metabolic effects of high-fat diet (HFD). There is growing awareness of the need to consider sex in disease progression, but limited attention has been paid to sexual dimorphism in mouse models and its impact in metabolic phenotypes. We assessed the effect of HFD and the impact of sex on metabolic variables in this strain. METHODS: We generated a reference data set encompassing glucose tolerance, body composition and plasma chemistry data from 586 C57BL/6N mice fed a standard chow and 733 fed a HFD collected as part of a high-throughput phenotyping pipeline. Linear mixed model regression analysis was used in a dual analysis to assess the effect of HFD as an absolute change in phenotype, but also as a relative change accounting for the potential confounding effect of body weight. RESULTS: HFD had a significant impact on all variables tested with an average absolute effect size of 29%. For the majority of variables (78%), the treatment effect was modified by sex and this was dominated by male-specific or a male stronger effect. On average, there was a 13.2% difference in the effect size between the male and female mice for sexually dimorphic variables. HFD led to a significant body weight phenotype (24% increase), which acts as a confounding effect on the other analysed variables. For 79% of the variables, body weight was found to be a significant source of variation, but even after accounting for this confounding effect, similar HFD-induced phenotypic changes were found to when not accounting for weight. CONCLUSION: HFD and sex are powerful modifiers of metabolic parameters in C57BL/6N mice. We also demonstrate the value of considering body size as a covariate to obtain a richer understanding of metabolic phenotypes

Turbulent swirling flow in a model of a uniflow-scavenged two-stroke engine

The turbulent and swirling flow of a uniflow-scavenged two-stroke engine cylinder is investigated using a scale model with a static geometry and a transparent cylinder. The swirl is generated by 30 equally spaced ports with angles of 0°,10°,20°, and 30°. A detailed characterization of the flow field is performed using stereoscopic particle image velocimetry. Mean fields are calculated using both a fixed coordinate system and a coordinate system based on the instantaneous flow topology. Time-resolved measurements of axial velocity are performed with laser Doppler anemometry, and power spectra are calculated in order to determine vortex core precession frequencies. The results show a very different flow dynamics for cases with weak and strong swirl. In the strongly swirling cases, a vortex breakdown is observed. Downstream of the breakdown, the vortex becomes highly concentrated and the vortex core precesses around the exhaust valve, resulting in an axial suction effect at the vortex center. Mean fields based on the instantaneous flow topology are shown to be more representative than mean fields based on a fixed coordinate system in cases with significant variations in the swirl center locatio