Abstract
Maintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure. To understand the genetic and environmental factors that contribute to the regulation of body weight, an important first step is to establish the normal range of metabolic values and primary sources contributing to variability. Energy metabolism is measured by powerful and sensitive indirect calorimetry devices. Analysis of nearly 10,000 wild-type mice from two large-scale experiments revealed that the largest variation in energy expenditure is due to body composition, ambient temperature, and institutional site of experimentation. We also analyze variation in 2329 knockout strains and establish a reference for the magnitude of metabolic changes. Based on these findings, we provide suggestions for how best to design and conduct energy balance experiments in rodents. These recommendations will move us closer to the goal of a centralized physiological repository to foster transparency, rigor and reproducibility in metabolic physiology experimentation.
Highlights
Mice are an instructive tool for the study of human metabolism as they can mirror human physiology in their responses to age-related and diet-induced obesity, and their physiological compensations to resist weight loss (Speakman et al, 2007)
To understand the different components affecting mouse metabolism, cohorts of genetically identical mice were shipped to four independent US Mouse Metabolic Phenotyping Centers (MMPCs) and assessed longitudinally over 12 weeks in indirect calorimeters while on low-fat diet (LFD) or high-fat diet (HFD)
Regression plots of 24 hr average energy expenditure (EE) versus total body mass showed distinct site-specific metabolic rates which could be attributed to differences in body mass for mice on LFD or HFD (Figure 1C and D)
Summary
Mice are an instructive tool for the study of human metabolism as they can mirror human physiology in their responses to age-related and diet-induced obesity, and their physiological compensations to resist weight loss (Speakman et al, 2007). The study of genetic and environmental factors influencing energy balance using laboratory animals has been advanced by the introduction of indirect calorimetry systems (Even and Nadkarni, 2012). Indirect calorimeters measure metabolic rates using gas sensors to capture rates of change in O2 consumption and CO2 production within an open flow system. Physical activity is monitored by recording infrared beam breaks or using electromagnetic receivers. Food intake is measured using sensitive mass balances. Weight gain results when food intake outpaces metabolic rate. When food intake falls below metabolic rate, weight loss
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