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.

Keywords: cardiac hypertrophy; diet; sex and exercise; soy.

Fig. 1.

Voluntary cage wheel exercise in male and female mice eating a soy- or casein-based diet. A: average running distance (km/day) for every 24 h over the 21-day study period. B: average running time (h/day) for every 24 h over the 21-day study period. ANOVA interaction of sex × diet: P < 0.05, *P < 0.05, from males eating the casein-based diet and from females eating the soy-based diet.

Fig. 2.

Voluntary cage running speed in male and female mice eating a soy- or casein-based diet. A: average weekly running speed (km/h) for every 24-h period over the 21-day study period. B: total average running speed (km/h) for every 24 h over the 21-day study period. ANOVA main effect of diet: P < 0.01, *P < 0.05, females eating the soy-based diet.

Fig. 3.

Cardiac adaptation in sedentary and exercised male and female mice eating a soy- or casein-based diet. The impact of cardiac adaption is displayed to show the impact of sex (A and B) or diet (C and D). A: cardiac adaptation expressed as percent change from respective mean sedentary normalized heart weight comparing males and females eating a soy-based diet. B: cardiac adaptation comparing males and females eating a casein-based diet. C: cardiac adaptation expressed as percent change from respective mean sedentary normalized heart weight comparing males eating a soy- or casein-based diet. D: cardiac adaptation comparing females eating a soy- or casein-based diet. *P < 0.05, from values obtained sedentary animals. §P < 0.05.

Fig. 4.

Cardiac adaptation normalized to activity. Normalized heart weight (HW/BW) divided by mean distance (HW/distance) run in a given 24-h period. ANOVA interaction of sex × diet: P < 0.05, *P < 0.05, from males eating the casein-based diet and from females eating the soy-based diet.

Fig. 5.

The impact of exercise, diet, or sex on mRNA transcripts MyHCα and TNF-α. A: bar graph representation of MyHCα transcript expression as impacted by exercise, diet, or sex. B: bar graph representation of TNF-α transcript expression as impacted by exercise, diet, or sex. Experimental groups as follows: FSoy, female soy; FC, female casein; MSoy, male soy; MC, male casein; FS, female sedentary; FE, female exercise; MS, male sedentary; ME, male exercise; SoyS, soy sedentary; SoyE, soy exercise; CS, casein sedentary; CE, casein exercise.

Fig. 6.

Quantification of class I, IIa, and IIb histone deacetylase (HDAC) catalytic activity in cardiac tissue homogenates from sedentary and exercised male and female mice eating a soy- or casein-based diet. Cardiac left ventricular extracts from each experimental group was incubated with different HDAC substrates. Each bar graph represents exercise-dependent HDAC activity such relative to sedentary control counterparts. Left: class I-selective substrate and corresponding HDAC activity data. Middle: class IIa substrate and corresponding HDAC activity data. Right: Class IIb substrate and corresponding activity data.

Fig. 7.

AMPK and acetyl-CoA carboxylase (ACC) protein expression in sedentary and exercised male and female mice eating a soy- or casein-based diet. A: representative Western Blots of AMPKα, p-AMPK¹⁷², ACC, and p-ACC. B: sedentary: Western blots represented as dot blots of AMPKα (left) and ACC (right) in sedentary male (circles) and female (triangles) mice eating a soy (open symbols) or casein (closed symbols). Mean value represented by horizontal line. C: exercise: means ± SE fold change following the exercise protocol relative to each respective sedentary control. D: activity: means ± SE fold change following the exercise protocol relative to each respective sedentary control. *P < 0.05, from indicated groups. Experimental groups as follows: MSS, male soy sedentary; MCS, male casein sedentary; FSS, female soy sedentary; FCS, female casein sedentary; MSE, male soy exercise; MCE, male casein exercise; FSE, female soy exercise; FCE, female casein exercise.