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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 type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2020
Effective date (End): January 31, 2022
Field of knowledge:Biological Sciences - Physiology - Physiology of Effort
Principal Investigator:Claudio Alexandre Gobatto
Grantee:Pedro Paulo Menezes Scariot
Home 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)