title: Long-term leucine supplementation aggravates prolonged strenuous exercise-induced cardiovascular changes in trained rats.
abstract: What is the central question of this study? Can long-term leucine supplementation prevent prolonged strenuous endurance exercise induced cardiac injury? What is the main finding and its importance? Prolonged endurance exercise does not seem to exceed cardiac energetic capacity, hence it does not represent an energy threat to this organ, at least in trained subjects. However, it may induce, in susceptible individuals, a state of cardiac electrical instability, which has been associated with ventricular arrhythmias and sudden cardiac death. This situation might be worsened when combined with leucine supplementation, which leads to increased blood pressure and cardiac injury. Leucine supplementation failed to prevent cardiac fatigue symptoms and may aggravate prolonged strenuous exercise-induced cardiovascular disturbances in trained rats. Observational studies have raised concerns that prolonged strenuous exercise training may be associated with increased risk of cardiac arrhythmia and even primary cardiac arrest or sudden death. It has been demonstrated that leucine can reduce prolonged exercise-induced muscle damage and accelerate the recovery process. The aim of this study was to investigate the effects of prolonged strenuous endurance exercise on cardiovascular parameters and biomarkers of cardiac injury in trained adult male rats and assess the use of leucine as an auxiliary substance to prevent the likely cardiac adverse effects caused by strenuous exercise. Twenty-four male Wistar rats were randomly allocated to receive a balanced control diet (18% protein) or a leucine-rich diet (15% protein plus 3% leucine) for 6 weeks. The rats were submitted to 1 h of exercise, 5 days per week for 6 weeks. Three days after the training period, the rats were submitted to swimming exercise until exhaustion, and cardiac parameters were assessed. Exercising until exhaustion significantly increased cardiac biomarker levels, cytokines and glycogen content inhibited protein synthesis signalling and led to cardiac electrical disturbances. When combined with exercise, leucine supplementation led to greater increases in the aforementioned parameters and also a significant increase in blood pressure and protein degradation signalling. We report, for the first time, that leucine supplementation not only fails to prevent cardiac fatigue symptoms, but may also aggravate prolonged strenuous exercise-induced cardiovascular disturbances in trained rats. Furthermore, we find that exercising until exhaustion can cause cardiac electrical disturbances and damage cardiac myocytes.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), 13083-862 Campinas, São Paulo, Brazil.|Sport Science Department, Faculty of Physical Education, Metropolitan College of Campinas (Metrocamp), 13035-270 Campinas, São Paulo, Brazil.
authors.forename: Gustavo Barbosa
authors.initials: GB
authors.lastname: Dos Santos
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), 13083-862 Campinas, São Paulo, Brazil.
authors.forename: André Gustavo
authors.initials: AG
authors.lastname: de Oliveira
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), 13083-862 Campinas, São Paulo, Brazil.
authors.forename: Luiz Alberto Ferreira
authors.initials: LA
authors.lastname: Ramos
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), 13083-862 Campinas, São Paulo, Brazil.
authors.forename: Maria Cristina Cintra
authors.initials: MC
authors.lastname: Gomes-Marcondes
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), 13083-862 Campinas, São Paulo, Brazil.
authors.forename: Miguel Arcanjo
authors.initials: MA
authors.lastname: Areas
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control*; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004032:Diet / Q000379:methods; D019587:Dietary Supplements; D005221:Fatigue / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000502:physiology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006003:Glycogen; D007930:Leucine