Lactate Profile and Fat Oxidation During Exercise
Condition: Energy Metabolism
Study type: Interventional

Summary: 
      The goal of this clinical trial is to test whether changes in lactate kinetics during
      exercise (due to glycogen depletion or hyperthermia) alter the pattern of fat oxidation
      during a maximal incremental cycle ergometer test in healthy young active people. The main
      questions it aims to answer are:

        -  Will a rightward shift in lactate kinetics, induced by a previous glycogen depletion,
           produce a rightward shift in fat oxidation?

        -  Will a leftward shift in lactate kinetics due to an increase in ambient temperature
           produce a leftward shift in fat oxidation?

      Participants will perform three maximal incremental tests in three different conditions:

        -  one in the control condition;

        -  one with glycogen depletion;

        -  and one with ambient heat (the latter two in randomized, counterbalanced order).
    

Detailed description: 
      Introduction Lactate has three major functions: it is an energy substrate, it is a
      gluconeogenic precursor, and it is a signalling molecule (1). Among the signalling functions
      is that of modulating skeletal muscle metabolism, as a regulator of fat oxidation at both the
      autocrine and paracrine levels. At the autocrine level, lactate increases the levels of
      Acetyl-coenzyme A (CoA) inside the mitochondria and, consequently, the levels of Malonyl-CoA.
      The increase in Malonyl-CoA concentration inhibits Carnitine PalmitoylTransferase 1 (CPT1),
      which is one of the transporters of fatty acids into the mitochondria (2). At the paracrine
      level, an increase in blood lactate concentration reduces the release of fatty acids into the
      blood by adipose tissue (3). This occurs because the G protein-coupled receptor present in
      adipose tissue inhibits the release of fatty acids into the blood when the blood lactate
      concentration increases (4). However, in vivo, only an inverse correlation between blood
      lactate concentration and fatty acid oxidation has been demonstrated (5,6). Therefore, the
      main objective of the study is to observe whether the pattern of fat oxidation during a
      maximal incremental cycle ergometer trial is altered due to changes in lactate kinetics
      during the given trial. For this purpose, three maximal trials will be performed with the
      same loading protocol (intensity and progression of the same), but different physiological
      conditions (normal vs. previous glycogen depletion vs. environmental hyperthermia).

      Procedures Consent to participate (signature of informed consent) will be requested from all
      volunteers who meet the inclusion criteria.

      The tests that will be performed throughout this study will be the following:

        1. At the first appointment, you will be asked about your medical history. Then, if
           appropriate, an assessment of your body composition by dual X-ray absorptiometry (DEXA)
           will be performed,

        2. In the second appointment, spirometry, an electrocardiogram at rest, and finally, an
           ergospirometric trial will be performed.

        3. In the third, fourth, and fifth visits, three maximal exercise trials will be performed,
           one each day. Of the three maximum ergospirometric trials that will be performed, one
           will be in a hot environment -approximately 38º Celsius (ºC) ambient temperature- and
           the other in a state of glycogen depletion. A glycogen depletion protocol and a
           low-carbohydrate diet will be performed before the maximal ergospirometric trial in the
           glycogen-depleted state, while the other two trials (simple maximal trial and
           hot-environment maximal trial) will be performed after 24h of a high-carbohydrate diet.

        4. The order of performance of each protocol will be randomized, provided that the glycogen
           depletion protocol is performed at the visit prior to the maximal ergospirometric trial
           under glycogen depletion. The depletion protocol consists of a 60-minute continuous
           cycle ergometer effort at the power associated with 60% of the maximal oxygen uptake
           (VO2) followed by six 30-second maximal efforts with four minutes of recovery. After
           this glycogen depletion exercise protocol, the participant will follow a
           low-carbohydrate diet (2% carbohydrate, 78% fat, and 20% protein), until the time of the
           ergospirometric trial under glycogen depletion status.
    

Intervention name(s): Incremental exercise test; Incremental exercise test under hyperthermia; Incremental exercise test under glycogen depletion
Intervention type(s): Other; Other; Other
Intervention description(s): Maximal incremental exercise test on a cycle ergometer (5 min warm-up at 30W, and subsequent steps of 3 min with power increases of 30W); Maximal incremental exercise test on a cycle ergometer (5 min warm-up at 30W, and subsequent steps of 3 min with power increases of 30W) performed at a room temperature of 35-38ºC (degrees Celsius).; Maximal incremental exercise test on a cycle ergometer (5 min warm-up at 30W, and subsequent steps of 3 min with power increases of 30W) under glycogen depletion by performing an exercise protocol to deplete glycogen stores plus a low-carbohydrate diet 24 h before incremental testing
Other intervention name(s): Maximal incremental ergometry; Maximal incremental ergometry with hyperthermia; Maximal incremental ergometry with glycogen depletion
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: lactate kinetics; exercise; energy metabolism; hyperthermia; glycogen depletion