Diet and sex modify exercise and cardiac adaptation in the mouse.
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.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado; Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona; konhilas@arizona.edu.
John P
JP
Konhilas
Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona;
Hao
H
Chen
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado;
Elizabeth
E
Luczak
Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona;
Laurel A
LA
McKee
Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona;
Jessica
J
Regan
University of Colorado Denver, and Department of Medicine, Division of Cardiology, University of Colorado, Denver, Colorado;
Peter A
PA
Watson
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado; Department of Medicine, Division of Cardiology, University of Colorado, Denver, Colorado; Department of Medicine, Division of Cardiology, Denver Health Medical Center, Denver, Colorado;
Brian L
BL
Stauffer
Department of Surgery, University of Arizona, Tucson, Arizona; and.
Zain I
ZI
Khalpey
Department of Medicine, Division of Cardiology, University of Colorado, Denver, Colorado;
Timothy A
TA
Mckinsey
Department of Medicine, Division of Cardiology, University of Colorado, Denver, Colorado;
Todd
T
Horn
Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.
Bonnie
B
LaFleur
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado;
Leslie A
LA
Leinwand
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D059267:Cardiomegaly, Exercise-Induced; D002364:Caseins / Q000009:adverse effects / Q000494:pharmacology; D004032:Diet; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D005082:Physical Exertion; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D030262:Soybean Proteins / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D002364:Caseins; D012333:RNA, Messenger; D030262:Soybean Proteins; D053773:Transforming Growth Factor beta1; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase
cardiac hypertrophy; diet; sex and exercise; soy