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CC BY-NC-ND 4.0 · Sports Med Int Open 2020; 4(01): E13-E18
DOI: 10.1055/a-1115-6373
Physiology & Biochemistry
Eigentümer und Copyright ©Georg Thieme Verlag KG 2020

Sex Differences in Cardiac AMP-Activated Protein Kinase Following Exhaustive Exercise

Kevin D. Brown‡
1   Division of Kinesiology & Health, University of Wyoming, College of Health Sciences, Laramie, United States
,
Edward D. Waggy‡
1   Division of Kinesiology & Health, University of Wyoming, College of Health Sciences, Laramie, United States
,
Sreejayan Nair 
2   School of Pharmacy, University of Wyoming, Laramie, United States
3   WWAMI Medical Education, University of Wyoming, Laramie, United States
,
Timothy J. Robinson
3   WWAMI Medical Education, University of Wyoming, Laramie, United States
,
Emily E. Schmitt
1   Division of Kinesiology & Health, University of Wyoming, College of Health Sciences, Laramie, United States
3   WWAMI Medical Education, University of Wyoming, Laramie, United States
,
Danielle R Bruns
1   Division of Kinesiology & Health, University of Wyoming, College of Health Sciences, Laramie, United States
3   WWAMI Medical Education, University of Wyoming, Laramie, United States
,
D.Paul Thomas
1   Division of Kinesiology & Health, University of Wyoming, College of Health Sciences, Laramie, United States
› Author Affiliations Funding: This study was supported by funding from the College of Health Sciences at the University of Wyoming to KDB and EDW (now deceased, “Ed you will be sorely missed”).
Further Information

Publication History

received 23 December 2019
revised 25 January 2020

accepted 05 February 2020

Publication Date:
20 March 2020 (online)

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Abstract

Ischemic heart disease presents with significant differences between sexes. Endurance exercise protects the heart against ischemic disease and also distinctly impacts male and female patients through unidentified mechanisms, though some evidence implicates 5′-AMP-activated protein kinase (AMPK). The purpose of this investigation was to assess the impact of training and sex on cardiac AMPK activation following exhaustive exercise. AMPK activation was measured in trained and sedentary mice of both sexes. Trained mice ran on a treadmill at progressively increasing speeds and duration for 12 weeks. Trained and sedentary mice of both sexes were euthanized immediately following exhaustive exercise and compared to sedentary controls. Endurance training elicited adaptations indicative of aerobic adaptation including higher max running velocities and cardiac hypertrophy with no differences between males and females. AMPK activity was higher in male compared to females, and trained exhibited higher AMPK activity compared to sedentary mice. In response to training, male mice activated AMPK more robustly than female mice. Chronic exercise training increases the ability to activate cardiac AMPK in response to exhaustive exercise in a sex-specific manner. Understanding the interaction between exercise and sex is vital for use of exercise as medicine for heart disease in both men and women.

Keywords

sex differences - cardiac - exercise - AMPK
 

  • References

  • 1 Maric-Bilkan C, Arnold AP, Taylor DA. et al. Report of the National Heart, Lung, and Blood Institute Working Group on Sex Differences Research in Cardiovascular Disease: Scientific Questions and Challenges. Hypertension 2016; 67: 802-807. doi:10.1161/HYPERTENSIONAHA.115.06967
    CrossrefPubMedGoogle Scholar
  • 2 Xu J, Kochanek KD, Murphy SL. et al. Deaths: Final Data for 2007. National Vital Statistics Reports 2010; 58: 1-135
    PubMedGoogle Scholar
  • 3 Mosca L, Hammond G, Mochari-Greenberger H. et al. Fifteen-year trends in awareness of heart disease in women: results of a 2012 American Heart Association national survey. Circulation 2013; 127: 1254-1263 e1251-1229. doi:10.1161/CIR.0b013e318287cf2f
    CrossrefPubMedGoogle Scholar
  • 4 Blenck CL, Harvey PA, Reckelhoff JF. et al. The importance of biological sex and estrogen in rodent models of cardiovascular health and disease. Circ Res 2016; 118: 1294-1312. doi:10.1161/CIRCRESAHA.116.307509
    CrossrefPubMedGoogle Scholar
  • 5 Lee DC, Sui X, Artero EG. et al. Long-term effects of changes in cardiorespiratory fitness and body mass index on all-cause and cardiovascular disease mortality in men: The Aerobics Center Longitudinal Study. Circulation 2011; 124: 2483-2490. doi:10.1161/CIRCULATIONAHA.111.038422
    CrossrefPubMedGoogle Scholar
  • 6 Qi D, Young LH. AMPK: energy sensor and survival mechanism in the ischemic heart. Trends Endocrinol Metab 2015; 26: 422-429 doi:10.1016/j.tem.2015.05.010
    PubMedGoogle Scholar
  • 7 Russell RR, Li J, Coven DL. et al. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest 2004; 114: 495-503
    CrossrefPubMedGoogle Scholar
  • 8 Kristiansen SB, Solskov L, Jessen N. et al. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside increases myocardial glucose uptake during reperfusion and induces late pre-conditioning: Potential role of AMP-activated protein kinase. Basic Clin Pharmacol Toxicol 2009; 10-16
    PubMedGoogle Scholar
  • 9 Brown DA, Jew KN, Sparagna GC. et al. Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart. J Appl Physiol 2003; 95: 2510-2518
    CrossrefPubMedGoogle Scholar
  • 10 Roepstorff C, Thiele M, Hillig T. et al. Higher skeletal muscle 2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise. J Physiol 2006; 574: 125-138. doi:10.1113/jphysiol.2006.108720
    CrossrefPubMedGoogle Scholar
  • 11 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817. doi:10.1055/a-1015-3123
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Wolff AM, Rasmussen TP, Wichern CR. et al. Effects of pericardiectomy on training- and myocardial infarction-induced left ventricular hypertrophy, chamber dimensions and gene expression. Int J Sports Med 2017; 38: 27-34. doi:10.1055/s-0042-115567
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Kemi OJ, Loennechen JP, Wisloff U. et al. Intensity-controlled treadmill running in mice: cardiac and skeletal muscle hypertrophy. J Appl Physiol (1985) 2002; 93: 1301-1309 doi:10.1152/japplphysiol.00231.2002
    CrossrefPubMedGoogle Scholar
  • 14 Davies SP, Carling D, Hardie DG. Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay. Eur J Biochem 1989; 186: 123-128
    CrossrefPubMedGoogle Scholar
  • 15 Shen QW, Means WJ, Underwood KR. et al. Early post-mortem AMP-activated protein kinase (AMPK) activation leads to phosphofructokinase-2 and -1 (PFK-2 and PFK-1) phosphorylation and the development of pale, soft, and exudative (PSE) conditions in porcine longissimus muscle. J Agric Food Chem 2006; 54: 5583-5589 doi:10.1021/jf060411k
    CrossrefPubMedGoogle Scholar
  • 16 Coven DL, Hu X, Cong L. et al. Physiological role of AMP-activated protein kinase in the heart: Graded activation during exercise. Am J Physiol Endocrinol Metab 2003; 285: E629-E636. doi:10.1152/ajpendo.00171.2003
    CrossrefPubMedGoogle Scholar
  • 17 Konhilas JP, Chen H, Luczak E. et al. Diet and sex modify exercise and cardiac adaptation in the mouse. Am J Physiol Heart Circ Physiol 2015; 308: H135-H145. doi:10.1152/ajpheart.00532.2014
    CrossrefPubMedGoogle Scholar
  • 18 Zawada I, Masternak MM, List EO. et al. Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver. Aging (Albany NY) 2015; 7: 195-204. doi:10.18632/aging.100733
    CrossrefPubMedGoogle Scholar
  • 19 Brown DA, Lynch JM, Armstrong CJ. et al. Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced cardioprotection are sex-dependent in the rat. J Physiol 2005; 564: 619-630 doi:jphysiol.2004.081323
    PubMedGoogle Scholar
  • 20 Lipovka Y, Chen H, Vagner J. et al. Oestrogen receptors interact with the alpha-catalytic subunit of AMP-activated protein kinase. Biosci Rep 2015; 35. doi:10.1042/BSR20150074
    PubMedGoogle Scholar
  • 21 Williams RL, Wood LG, Collins CE. et al. Effectiveness of weight loss interventions – is there a difference between men and women: A systematic review. Obes Rev 2015; 16: 171-186. doi:10.1111/obr.12241
    CrossrefPubMedGoogle Scholar
  • 22 Musi N, Hirshman MF, Arad M. et al. Functional role of AMP-activated protein kinase in the heart during exercise. FEBS Lett 2005; 579: 2045-2050. doi:10.1016/j.febslet.2005.02.052
    CrossrefPubMedGoogle Scholar