Diet and sex modify exercise and cardiac adaptation in the mouse

John P. Konhilas, Hao Chen, Elizabeth Luczak, Laurel A. McKee, Jessica Regan, Peter A. Watson, Brian L. Stauffer, Zain I. Khalpey, Timothy A. McKinsey, Todd Horn, Bonnie LaFleur, Leslie A. Leinwand

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)H135-H145
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1
StatePublished - 2015


  • Cardiac hypertrophy
  • Diet
  • Sex and exercise
  • Soy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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