Effects of aerobic training and the hypoxic environment on molecular responses related to anaerobic and aerobic metabolism and acid-base properties in the hypothalamus and skeletal muscle of mice

• Grant number: 19/05115-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2020
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Claudio Alexandre Gobatto
• Grantee: Pedro Paulo Menezes Scariot
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

In 1997, Levine and Stray-Gundersen conceived the idea that athletes living at altitude (hypoxia) and training at low altitude (normoxia) could improve the physical fitness. This model known as "Living High and Training Low" (LH-TL), became very appreciated in the exercise physiology. Although such model seems effective for athletes, it is still necessary to understand the adaptive physiological in the inaccessible tissues in humans, but possible in laboratory rodents. It is essential to determine if the LH-TL model is capable of affecting the anaerobic and aerobic metabolism together with acid-base control are understood or even energy balance. We have in energy balance because there is evidence indicating that food consumption and Spontaneous Physical Activity (SPA) are reduced in animals exposed to hypoxia. SPA represents all non-voluntary physical activities of daily living, such as posture maintenance, ambulation, which have a significant contribution to daily energy expenditure. Our aim will be to investigate the effects of aerobic physical training and hypoxic environment on and molecular responses related to anaerobic and aerobic metabolism and acid-base properties as well as energy balance in the hypothalamus and skeletal muscle of C57BL/6J mice. Because they are central regulators in anaerobic and aerobic metabolism, we will study the protein concentrations of HIF-1± (Hypoxia-Inducible Factor) and PGC-1± (Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha). In order to evaluate the control of SPA and food intake we will determine the protein content of the orexin receptors, called OX1R and OX2R, as well as the neuropeptide Y (NPY) and Agouti related peptide (AgRP) in the hypothalamus, and the serum concentrations of orexin-A and leptin. Still in this tissue, we will quantify the protein contents of the monocarboxylic transporters (MCTs), isoforms 1, 2 and 4, which are related to acid-base properties. At the peripheral level, the protein expression of HIF-1±, PGC-1±, MCT-1 and MCT-4 will be quantified in the soleus (oxidative) and gastrocnemius (white portion, glycolytic) muscles. We will determine the biometric and glycogen content in different animal tissues. Thus, forty C57BL/6J mice will be divided into two housing conditions: normoxia or hypoxia. For each type of environmental condition, mice will be subdivided into two groups: Control (C) or Trained (T). Animals will be exposed to the hypoxic environment daily (18 hours.day-1) at an inspired fraction of oxygen equivalent to 14.5% (~ 3000m atmosphere). For mice of T group, the aerobic training program will be applied under normoxia conditions. Each training session will have a daily volume of 40min with weekly frequency of five days performed in intensity equivalent to 80% of the critical velocity. Throughout the experiment, the feeding behavior of the animals will be evaluated, as well as the SPA (in loco) by means of a gravimetric system. Aerobic and anaerobic capacities in running exercise will be evaluated by the critical velocity protocol. At the end of the experiment, the mice will be euthanized for with drawal of samples from the hypothalamus and the soleus and gastrocnemius muscles. Investigations about the molecular responses related to anaerobic and aerobic metabolism, acid-base control and energy balance are crucial for the full understanding of the association between exposure to hypoxia and aerobic physical training. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BREDA, FABIO LEANDRO; MANCHADO-GOBATTO, FULVIA BARROS; DE BARROS SOUSA, FILIPE ANTONIO; BECK, WLADIMIR RAFAEL; PINTO, ALLAN; PAPOTI, MARCELO; MENEZES SCARIOT, PEDRO PAULO; GOBATTO, CLAUDIO ALEXANDRE. omplex networks analysis reinforces centrality hematological role on aerobic-anaerobic performances of the Brazilian Paralympic endurance team after altitude trainin. SCIENTIFIC REPORTS, v. 12, n. 1, JAN 21 2022. (20/11946-6, 19/05115-7, 19/16253-1, 13/16710-7, 16/12781-5, 09/08535-5, 12/06355-2)

SCARIOT, PEDRO P. M.; MANCHADO-GOBATTO, FULVIA B.; VAN GINKEL, PAUL R.; PROLLA, TOMAS A.; GOBATTO, CLAUDIO A.. Aerobic training associated with an active lifestyle exerts a protective effect against oxidative damage in hypothalamus and liver: The involvement of energy metabolism. Brain Research Bulletin, v. 175, p. 116-129, OCT 2021. (17/10201-4, 19/05115-7, 15/01362-9, 15/00272-6)

SCARIOT, PEDRO PAULO MENEZES; PAPOTI, MARCELO; POLISEL, EMANUEL ELIAS CAMOLESE; ORSI, JUAN BORDON; GINKEL, PAUL R. VAN; PROLLA, TOMAS A.; MANCHADO-GOBATTO, FULVIA BARROS; GOBATTO, CLAUDIO ALEXANDRE. Living high- training low model applied to C57BL/6J mice: Effects on physiological parameters related to aerobic fitness and acid-base balance. Life Sciences, v. 317, p. 17-pg., 2023-02-01. (17/10201-4, 15/00272-6, 15/01362-9, 19/05115-7, 16/12781-5)

SCARIOT, P. P. M.; MANCHADO-GOBATTO, F. B.; BECK, W. R.; PAPOTI, M.; VAN GINKEL, P. R.; GOBATTO, C. A.. Monocarboxylate transporters (MCTs) in skeletal muscle and hypothalamus of less or more physically active mice exposed to aerobic training. Life Sciences, v. 307, p. 11-pg., 2022-08-11. (18/07099-6, 17/10201-4, 19/05115-7, 15/01362-9, 15/00272-6, 14/10336-9)

POLISEL, EMANUEL E. C.; BECK, WLADIMIR R.; SCARIOT, PEDRO P. M.; PEJON, TACIANE M. M.; GOBATTO, CLAUDIO A.; MANCHADO-GOBATTO, FULVIA B.. Effects of high-intensity interval training in more or less active mice on biomechanical, biophysical and biochemical bone parameters. SCIENTIFIC REPORTS, v. 11, n. 1, MAR 19 2021. (15/00272-6, 18/07099-6, 19/05115-7, 15/01362-9, 19/08148-3, 14/10336-9, 17/10201-4)

SCARIOT, PEDRO P. M.; GOBATTO, CLAUDIO A.; POLISEL, EMANUEL E. C.; GOMES, ANA E. C.; BECK, WLADIMIR R.; MANCHADO-GOBATTO, FULVIA B.. Early-life mice housed in standard stocking density reduce the spontaneous physical activity and increase visceral fat deposition before reaching adulthood. LABORATORY ANIMALS, v. N/A, p. 12-pg., 2022-01-21. (17/10201-4, 14/10336-9, 19/08148-3, 15/01362-9, 15/00272-6, 18/07099-6, 19/05115-7)