Diet and sex modify exercise and cardiac adaptation in the mouse

Abstract

The heart adapts to exercise stimuli in a sex-dimorphic manner when mice are fed the traditional soy-based chow. Females undergo more voluntary exercise (4 wk) than males and exhibit more cardiac hypertrophy per kilometer run (18, 32). We have found that diet plays a critical role in cage wheel exercise and cardiac adaptation to the exercise stimulus in this sex dimorphism. Specifically, feeding male mice a casein-based, soy-free diet increases daily running distance over soy-fed counterparts to equal that of females. Moreover, casein-fed males have a greater capacity to increase their cardiac mass in response to exercise compared with soy-fed males. To further explore the biochemical mechanisms for these differences, we performed a candidate-based RT-PCR screen on genes previously implicated in diet- or exercise-based cardiac hypertrophy. Of the genes screened, many exhibit significant exercise, diet, or sex effects but only transforming growth factor-β1 shows a significant three-way interaction with no genes showing a two-way interaction. Finally, we show that the expression and activity of adenosine monophosphate-activated kinase-α2 and acetyl-CoA carboxylase is dependent on exercise, diet, and sex.

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

“…Consistent with previous studies (Lerman et al, 2002; Massett and Berk, 2005), we found that C57BL/6J mice have lower treadmill exercise capacity, which did not improve even when they were tested at night. Nevertheless, several studies show that C57BL/6J mice are quite adept at voluntary wheel exercise (e.g., Katzeff et al, 1988; Carter et al, 1995; Lerman et al, 2002; Massett and Berk, 2005; Werner et al, 2008, 2009; Falls et al, 2010; Konhilas et al, 2015), even load bearing wheels which simulate resistance training (Konhilas et al, 2005); and, consistent with their nocturnal behavior, wheel activity in C57BL/6J mice peaks during the night (Pugh et al, 2004). This suggests that the C57BL/6J strain is more amenable to the wheel running modality than treadmill exercise.…”

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

“…Interestingly, the mouse heart is able to recognize an intermittent, pathological overload meant to mimic the intermittent nature of an exercise load as distinctly pathological (Perrino et al, 2006). For this reason, we and others have employed a voluntary exercise paradigm, where rodents have free, unobstructed access to a cage wheel (Allen et al, 2001; Eldomiaty et al, 2016; Konhilas et al, 2015; Konhilas et al, 2004; McMullan et al, 2016). There is ample evidence that voluntary wheel running is a complex behavior resulting from natural rodent tendencies and laboratory environment (Konhilas et al, 2015; Meijer and Robbers, 2014; Richter et al, 2014).…”

“…For this reason, we and others have employed a voluntary exercise paradigm, where rodents have free, unobstructed access to a cage wheel (Allen et al, 2001; Eldomiaty et al, 2016; Konhilas et al, 2015; Konhilas et al, 2004; McMullan et al, 2016). There is ample evidence that voluntary wheel running is a complex behavior resulting from natural rodent tendencies and laboratory environment (Konhilas et al, 2015; Meijer and Robbers, 2014; Richter et al, 2014). Activity from cage wheel exercise generally improves depressive-like behaviors (Eldomiaty et al, 2016), although this is challenged by studies suggesting an anxiolytic or addictive-like component to wheel running (Duman et al, 2008; Fuss et al, 2010; Richter et al, 2014).…”

Sex‐dependent differences in voluntary physical activity

“…Wistar female rats exhibit elevated running rates relative to males regardless of being on ad libitum or food-restricted diet (Jones et al 1990). Likewise, female mice are more active, as exemplified by running an average of 6.5 ± 1.3 km compared to males who only run 3.9 ± 0.2 km in a 24 hour period, and show increased cardiac hypertrophy due to running than males (females = 15.5 ± 1.9% vs. males = 4.6 ± 0.5%) when both are maintained on a soy-based chow diet (Harlan Teklad 8640) (Konhilas et al 2015). However, males fed a casein-based diet (Research Diets D10001) demonstrate an increase in running distance and exercise-induced cardiac enlargement to levels approximating those of females maintained on this same diet (females = 17.5 ± 1.6% compared to males = 13.2 ± 2.7%).…”