McMullan RC, Ferris MT, Bell TA, Menachery VD, Baric RS, Hua K, Pomp D, Smith-Ryan AE, de Villena FP. CC002/Unc females are mouse models of exercise-induced paradoxical fat response.
Physiol Rep. 2018 Jun;6(12):e13716. doi: 10.14814/phy2.13716.
Rachel C McMullan University of North Carolina, Chapel Hill, NC|
Fernando Pardo-Manuel de Villena University of North Carolina, Chapel Hill, NC
With: Ferris MT, Bell TA, Menachery VD, Baric RS, Hua K, Pomp D, Smith-Ryan AE
|Contact||Fernando Pardo-Manuel de Villena firstname.lastname@example.org
|Acknowledgements||Funding provided by NIH DK056350, AI100625, AI109761, AG049092, MH100241, DK05350, Al100625|
|Phenotype archive study|
|MPD identifiers||McMullan5 MPD:614|
|No updates/corrections. Initial release date: 07/2018.|
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Purpose: To characterize CC002/Unc as a robust exercise-induced adverse fat response model in a controlled voluntary exercise study.
Mice: All mice were purchased from the Systems Genetics Core Facility (http://csbio.unc.edu/CCstatus/index.py) and housed in the Division of Comparative Medicine facilities at the University of North Carolina at Chapel Hill. All procedures performed within this experiment were approved by the University of North Carolina – Chapel Hill Institutional Animal Care and Use Committee (IACUC #15-015). Mice were housed in a temperature controlled (23° +/- 1° C) and humidity controlled vivarium with a standard 12:12h light:dark cycle (lights on at 0700h). Mice were allowed ad libitum access to standard laboratory chow (Envigo 2920 irradiated chow) and water.
Exercise treatment: Female mice (n=12 per strain; born September to October 2016) from CC002/Unc and CC037/TauUnc were used to assess robustness of the CC002/Unc model at a younger age (~4 months +/- 2 weeks) than tested in McMullan1 and McMullan4. Mice were assigned to control (CC002/Unc n=3; CC037/TauUnc n=5) or experimental (CC002/Unc n=9; CC037/TauUnc n=7) cohorts. Both cohorts were acclimated for two weeks to single housing with attached wheels in same vivarium room but without access to wheels. After acclimation, mice in the experimental cohort were given ad libitum access to running wheels for eight weeks. The control cohort did not have access to running wheels. Total weekly distance, total weekly duration and average weekly speed were calculated for each two week interval of wheel access and were labeled 1, 2, 3 and 4 (respectively: weeks 1-2, weeks 3-4, weeks 5-6, weeks 7-8 of wheel access).
Metabolic measurements: Body mass and composition were measured every two weeks over the 10 weeks of the experiment for all cohorts. Body composition was assessed (during mornings 0700-1200h) using whole body MRI (EchoMRI 3-in-1 Body Composition Analyzer, EchoMRI, Houston, TX) to determine fat and lean mass content (in grams) for each animal. Food was weighed at the same time points as body composition for both control and experimental cohorts.
Metabolic calculations: Body fat and lean mass percentages were calculated relative to body mass at each time point in every experiment. Body mass response was calculated as [(Post-mass – pre-mass)/pre-mass] x 100. Body composition percentage response was calculated as [(post-measurement % - pre-measurement %)/pre-measurement %] x 100. For each mouse, cumulative body mass and composition responses were calculated for every experimental time point interval (1, 2, 3, 4; respectively: weeks 0-2, weeks 0-4, weeks 0-6 and weeks 0-8 of treatment). Negative values represent a loss and positive values represent a gain in response to treatment. Food intake was calculated as the differential between baseline and post exercise food weights (g). Adjusted food intake was calculated as the food intake relative to the baseline body mass for each interval.
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