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

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.

Differences in Exercise Capacity and Responses to Training in 24 Inbred Mouse Strains

“…Conversely, several strains showed significant increases in endurance exercise capacity with training (129S1, CE/J, FVB/NJ, NOD/ShiLtJ, PL/J, SJL/J, and SWR/J). We, and others previously reported that FVB/NJ mice exhibit significant improvements in performance with exercise training (Massett and Berk, 2005 ; Chow et al, 2007 ; Massett et al, 2009 ; Gibb et al, 2016 ). Those changes in endurance exercise capacity were associated with physiological changes consistent with the expected cardiovascular and metabolic adaptations to training (Massett and Berk, 2005 ; Chow et al, 2007 ; Gibb et al, 2016 ), indicating this strain is useful for genetic and physiological studies of exercise training responses.…”

Modifications of Sarcoplasmic Reticulum Function Prevent Progression of Sarcomere-Linked Hypertrophic Cardiomyopathy Despite a Persistent Increase in Myofilament Calcium Response

“…Moreover, it has been previously presented in two HCM mouse models that mice expressing tropomyosin (Tm-E180G) developed a more pronounced hypertrophic phenotype in FVB/N than in C57BL/6 genetic background (Prabhakar et al, 2001;Michele et al, 2002), and in mice with a mutation in actin (ACTZ E99K), the probability of sudden cardiac death was almost completely eliminated in mice bred on C57/BL6 background (Rowlands et al, 2017). The importance of the mouse genetic background on the basal cardiac function, adaptations to exercise, or stress is also well-documented (Barnabei et al, 2010;Peng et al, 2011;Gibb et al, 2016).…”

Metabolic regulation of myocardial adaptation to exercise.

“…All studies began at 15 weeks of age; food and water were provided ad libitum; and the mice were maintained on a 12:12-h light-dark schedule, as described previously. 63 At the conclusion of animal experiments, and following a 6 h fast, mice were On the Friday immediately following treadmill familiarization, we subjected mice to an exercise capacity test. For this, the mice were acclimated to the treadmill for 10 min, with the speed and incline set initially to zero.…”

“…60 The most common metabolic adaptation of the heart to exercise is mitochondrial biogenesis. [61][62][63] While various signaling events likely lead to an increase in mitochondrial mass, exercise-induced increases in peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) play a critical role. 64 Interestingly, induction of PGC-1α in response to exercise was prevented in IGF1r knockout mice, and it has been shown that signaling through PI3K, but not AKT, is required for this biogenic response.…”

“…We chose this progressive intensity protocol to prevent training plateau and to stimulate systemic and cardiac adaptations. 63 To test the effects of chronic exercise in the adapted and recovery state, mice were euthanized 24 h or 1 h after the last training session of the 4 wk training regimen, respectively. To interrogate the effects of an acute, single-bout of exercise on cardiac metabolism, mice were subjected to familiarization as previously outlined and euthanized immediately following the completion of a 1 d, single exercise training session; 40 min at 75% intensity.…”