A big-data approach to understanding metabolic rate and response to obesity in laboratory mice
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 2,329 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.
Data availability
All data and code can be found at https://github.com/banks-lab/Cal-Repository. Repository data includes complete indirect calorimetry data for MMPC experiments including CalR files for 4 sites at 0, 4, and 11 week trials, our MMPC analysis database, corrected IMPC database, and additional data for Figures 5 and 7. The R code to reproduce all figures is also included.
Article and author information
Author details
Funding
National Institutes of Health (R01DK107717)
- Alexander Banks
National Institutes of Health (U24-DK092993)
- Jon J Ramsey
National Institutes of Health (U24-DK059635)
- Michael J Jurczak
National Institutes of Health (U24-DK076174)
- Owen P McGuinness
National Institutes of Health (U24-DK059637)
- Owen P McGuinness
National Institutes of Health (U24-DK059630)
- Owen P McGuinness
National Institutes of Health (U24-DK093000)
- Jason K Kim
National Institutes of Health (U24-DK076169)
- Alexander Banks
Swiss National Science Foundation (Postdoc mobility grant)
- Deepti Ramachandran
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: These studies were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) at the site where they were performed.
Copyright
© 2020, Corrigan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 8,311
- views
-
- 1,081
- downloads
-
- 53
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Immunology and Inflammation
- Neuroscience
Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.
-
- Computational and Systems Biology
- Neuroscience
Diffusional kurtosis imaging (DKI) is a methodology for measuring the extent of non-Gaussian diffusion in biological tissue, which has shown great promise in clinical diagnosis, treatment planning, and monitoring of many neurological diseases and disorders. However, robust, fast, and accurate estimation of kurtosis from clinically feasible data acquisitions remains a challenge. In this study, we first outline a new accurate approach of estimating mean kurtosis via the sub-diffusion mathematical framework. Crucially, this extension of the conventional DKI overcomes the limitation on the maximum b-value of the latter. Kurtosis and diffusivity can now be simply computed as functions of the sub-diffusion model parameters. Second, we propose a new fast and robust fitting procedure to estimate the sub-diffusion model parameters using two diffusion times without increasing acquisition time as for the conventional DKI. Third, our sub-diffusion-based kurtosis mapping method is evaluated using both simulations and the Connectome 1.0 human brain data. Exquisite tissue contrast is achieved even when the diffusion encoded data is collected in only minutes. In summary, our findings suggest robust, fast, and accurate estimation of mean kurtosis can be realised within a clinically feasible diffusion-weighted magnetic resonance imaging data acquisition time.