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.
Keywords: energy expenditure; food intake; genetics; human biology; medicine; metabolic rate; mouse; neuroscience; obesity; thermogenesis.
Maintaining a healthy weight requires the body to balance energy intake and expenditure. The body converts food to energy through a process called energy metabolism. Genetic and environmental factors can affect energy metabolism and energy balance contributing to conditions like obesity. To better understand metabolism, scientists often study mice in laboratories, but mice from different laboratories appear to convert food to energy at different rates. This makes it hard to determine what is ‘normal’ for mouse metabolism. These discrepancies could be due to small differences between how mice are kept in different laboratories. For example, the temperatures of the mouse cages or how active the mice are might differ depending on the laboratory. Identifying the effects of such differences is essential, but it requires looking at data from hundreds of mice. Corrigan et al. examined data from more than 30,000 mice at laboratories around the world to show that room temperatures and the amount of muscle and fat in a mouse’s body have the biggest influence on energy balance. These two factors affected the metabolism of both typical mice and mice with mutations that affect their energy balance. These results suggest that it is important for scientists to report factors like room temperatures, the body make-up of the mice, or the animals’ activity levels in metabolism studies. This can help scientists compare results and repeat experiments, which could speed up research into mouse metabolism. Corrigan et al. also found that other unknown factors also affect mouse metabolism in different laboratories. Further studies are needed to identify these factors.
© 2020, Corrigan et al.