Program in Molecular Medicine; Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine
Biochemical Phenomena, Metabolism, and Nutrition | Endocrinology, Diabetes, and Metabolism | Investigative Techniques | Nutritional and Metabolic Diseases | Pathological Conditions, Signs and Symptoms | Physiology
Maintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure. In humans and in laboratory mice these factors are experimentally measured by powerful and sensitive indirect calorimetry devices. 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 in results. Here we examine indirect calorimetry results from two experimental mouse projects, the Mouse Metabolic Phenotyping Centers and International Mouse Phenotyping Consortium to develop insights into large-scale trends in mammalian metabolism. Analysis of nearly 10,000 wildtype mice revealed that the largest experimental variances are consequences of institutional site. This institutional effect on variation eclipsed those of housing temperature, body mass, locomotor activity, sex, or season. We do not find support for the claim that female mice have greater metabolic variation than male mice. An analysis of these factors shows a normal distribution for energy expenditure in the phenotypic analysis of 2,246 knockout strains and establishes a reference for the magnitude of metabolic changes. Using this framework, we examine knockout strains with known metabolic phenotypes. We compare these effects with common environmental challenges including age, and exercise. We further examine the distribution of metabolic phenotypes exhibited by knockout strains of genes corresponding to GWAS obesity susceptibility loci. Based on these findings, we provide suggestions for how best to design and conduct energy balance experiments in rodents, as well as how to analyze and report data from these studies. These recommendations will move us closer to the goal of a centralized physiological repository to foster transparency, rigor and reproducibility in metabolic physiology experimentation.
Physiology, obesity, body weight, energy balance experiments, metabolism, laboratory mice
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.
DOI of Published Version
bioRxiv 839076; doi: https://doi.org/10.1101/839076. Link to preprint on bioRxiv service.
Corrigan JK, Ramachandran D, He Y, Palmer C, Jurczak MJ, Li B, Friedline RH, Kim JK, Ramsey JJ, Lantier L, McGuinness OP, Banks AS, Mouse Metabolic Phenotyping Center Energy Balance Working Group. (2019). A big-data approach to understanding metabolic rate and response to obesity in laboratory mice. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/839076. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1647
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This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.
Biochemical Phenomena, Metabolism, and Nutrition Commons, Endocrinology, Diabetes, and Metabolism Commons, Investigative Techniques Commons, Nutritional and Metabolic Diseases Commons, Pathological Conditions, Signs and Symptoms Commons, Physiology Commons