FVB/NJ Mice Are a Useful Model for Examining Cardiac Adaptations to Treadmill Exercise.

Andrew A Gibb,Daniel W Riggs,Daniel J Conklin,Aruni Bhatnagar,Lindsey A Mcnally,Bradford G Hill

doi:10.3389/fphys.2016.00636

Abstract

Mice are commonly used to examine the mechanisms by which exercise improves cardiometabolic health; however, exercise compliance and adaptations are often strain-dependent or are variable due to inconsistency in exercise training protocols. In this study, we examined nocturnal/diurnal behavior, treadmill exercise compliance, and systemic as well as cardiac-specific exercise adaptations in two commonly used mouse strains, C57BL/6J, and FVB/NJ mice. Metabolic cage analysis indicated a strong nocturnal nature of C57BL/6J mice, whereas FVB/NJ mice showed no circadian element to activity, food or water intake, VO2, or VCO2. Initial exercise capacity tests revealed that, compared with C57BL/6J mice, FVB/NJ mice are capable of achieving nearly 2-fold higher workloads prior to exhaustion. FVB/NJ mice tested during the day were capable of achieving significantly more work compared with their night-tested counterparts. Following 4 weeks of training, FVB/NJ mice showed significant increases in exercise capacity as well as physiologic cardiac growth characterized by enlarged myocytes and higher mitochondrial DNA content. C57BL/6J mice showed no increases in exercise capacity or cardiac growth regardless of whether they exercised during the day or the night. This lack of adaptation in C57BL/6J mice was attributable, at least in part, to their progressive loss of compliance to the treadmill training protocol. We conclude that the FVB/NJ strain is a useful and robust mouse model for examining cardiac adaptations to treadmill exercise and that treadmill training during daytime hours does not negatively affect exercise compliance or capacity.

Highlights

Regular exercise improves cardiovascular health (Blair et al, 1996; Mora et al, 2007; Joyner and Green, 2009), augments musculoskeletal function (Egan and Zierath, 2013), and increases both healthspan (Mercken et al, 2012; Egan and Zierath, 2013; de Cabo et al, 2014) and lifespan (Paffenbarger et al, 1986; Blair et al, 1989, 1996; Myers et al, 2002)
Our study demonstrates that FVB/NJ mice are a superior strain for treadmill exercise and that the timing of treadmill exercise, at least in this strain, does not influence compliance or exercise-induced adaptation
We found that C57BL/6J mice have significantly lower treadmill exercise capacity compared with FVB/NJ mice

Summary

Introduction

Regular exercise improves cardiovascular health (Blair et al, 1996; Mora et al, 2007; Joyner and Green, 2009), augments musculoskeletal function (Egan and Zierath, 2013), and increases both healthspan (Mercken et al, 2012; Egan and Zierath, 2013; de Cabo et al, 2014) and lifespan (Paffenbarger et al, 1986; Blair et al, 1989, 1996; Myers et al, 2002). Mouse models cannot perfectly recapitulate the complex physiological changes occurring in humans with physical activity, they can phenocopy particular aspects of physiological adaptation For this purpose, three models of mouse exercise are used frequently: treadmill training, forced swimming, and voluntary wheel running. Three models of mouse exercise are used frequently: treadmill training, forced swimming, and voluntary wheel running While each of these models have advantages and limitations (Bernstein, 2003; Wang et al, 2010), treadmill training provides the investigative advantage of being able to control the amount of work performed in each training session. These include, but are not limited to, mouse strain, exercise environment, acclimatization, motivation, and assessments of exhaustion (Perrino et al, 2011; Platt et al, 2015)

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