The Effect of Exercise on Metabolic Alteration

The goal of this clinical trial is to study the effectiveness of aerobic exercise in treating obesity in adults and to assess the efficacy of exercise. The primary research questions it seeks to address are as follows:

* To what extent does exercise increase the total energy expenditure of participants?
* Why and how does the energy expenditure from exercise not fully compensate for the total energy expenditure (TEE)?
* Researchers will assess the efficacy and potential challenges of using exercise as a treatment for obesity by comparing the measurement data before exercise intervention (week 0), immediately after exercise intervention (week 12), and 8 weeks post-completion of exercise intervention (week 20).

Participants will engage in the following activities:

* Engage in running sessions supervised five times a week for a duration of 12 weeks.
* Attend laboratory sessions both before and after the exercise intervention period for metabolic and anthropometric measurements, as well as sample collection.
* Return to the laboratory for further metabolic and anthropometric measurements and sample collection8 weeks post-completion of exercise intervention.

Based on previous research findings, scientists found that exercise results in energy compensation. In a non-interventional setting, energy intake and expenditure undergo a dynamic equilibrium process. Nonetheless, the energy deficit induced by exercise is offset by other physiological or psychological behaviors, leading to a diminished energy discrepancy caused by exercise, thereby mitigating the weight loss effects typically associated with exercise(Pontzer et al 2016: Current Biology).Controlled dietary experiments have indicated that long-term exercise results in approximately 22% energy compensation (Bouchard et al 1994: Obesity Research); however, the underlying source and mechanism of this compensation remains ambiguous. Analyses of Total Energy Expenditure (TEE) in 1754 individuals have demonstrated that the energy compensation from exercise primarily emanates from a reduction in Basal Energy Expenditure (BEE), with only an average of 72% of the energy expended during exercise being utilized for additional energy expenditure (Careau et al 2021: Current Biology). Nevertheless, this deduction is restricted by the measurements of energy intake, Adaptive thermogenesis, Thermic Effect of Food (TEF), and Activity-related Energy Expenditure (AEE), emphasizing the necessity of exercise intervention studies to comprehensively grasp the pathways and mechanisms of energy compensation.

To tackle the challenges posed by overweight and obesity, enhance residents' quality of life, and delve deeper into the intricacies of energy compensation, this research project focuses on examining the metabolic reactions of the body to exercise interventions. Through the analysis of pre- and post-exercise energy expenditure and intake, body composition, metabolism, microbiota, and metabolomics alterations in humans, the primary goal is to thoroughly elucidate the principal factors and mechanisms behind energy compensation. This clinical trial consists of four phases: pre-exercise intervention baseline measurement, exercise intervention, Immediately after 12 weeks' exercise intervention measurement, and follow-up measurement 8 weeks post-completion of the exercise intervention.

Pre-exercise intervention baseline measurement:

* Anthropometric measurements: body weight, height, and body composition

  * Body weight: At visit 1, fasting body weight will be measured using a calibrated seca at the beginning of the visit. Fasting weight will be measured at visit 2 and, if applicable.
  * Height: Height (to +0.1 cm) will be measured by seca 217 stable without wearing shoes.
  * Body composition:

    * Fat mass will be measured by Magnetic Resonance Imaging (MRI, Shanghai united imaging, uMR 790 ).
    * Bioimpedance analysis will measure fat-free mass (Tanita, MC-980).
    * Bone mass will be measured by Dual Energy X-ray Absorptiometry (DXA, Horizon Wi, HOLOGIC).
* Metabolic measurements: blood pressure, glucose, heart rate, energy expenditure, and cardiovascular function

  * Blood pressure： Systolic and diastolic blood pressure will be measured using an Omron digital sphygmomanometer.
  * Blood glucose： Fasting and post-prandial glucose will be recorded by a continuous glucose monitoring system.
  * Heart rate：Heart rate will be monitored by a continuous heart rate monitoring system.
  * Energy expenditure：

    * TEE will be measured using the doubly-labeled water (DLW) method. Urine samples from all participants in the DLW subset will be stored at -20℃ and shipped on dry ice for analysis in the laboratory of Prof. John Speakman at the Shenzhen Institutes of Advanced Technology, Chinese academy of sciences. Isotopes will be measured in benchtop near-infrared isotope gas analyzer, and mean CO2 production will be calculated from isotope ratios using the recently derived equation (Speakman et al 2021: Cell reports medicine). TEE will then be calculated using mean CO2 production.
    * Resting Energy Expenditure (REE) and TEF will be measured by indirect calorimetry while participants are resting supine in a respiratory chamber with thermoneutral conditions. Oxygen consumption and CO2 production will be measured to calculate energy expenditure. REE will be consistently measured throughout sleeping at night and in the morning after overnight fasting, and TEF will be measured after breakfast.
  * VO2max test：Participants must warm up with simple stretching or light aerobic exercise before the test. The test will be conducted on a treadmill. A comfortable running speed acceptable to the participant will be set. The treadmill's incline will be increased by 10% every two minutes until the individual reaches their physical limit and can no longer continue. During this test, a respiratory mask and gas analyzer will be used to measure the concentration of oxygen (O2) and carbon dioxide (CO2) in the breath to calculate VO2max.
* Sample collection: Serum(vein blood extraction from the wrist or elbow by a nurse with a nursing qualification), feces, and urine
* Behaviour monitor: physical activity and food intake.

  * Physical activity：Physical activity of the participants will be recorded using GT3X accelerometer worn near the hip for a consecutive period of 14 days. The monitor should not be worn while bathing or swimming. The first day is discarded along with any day with less than 12 hours of wear. For a valid measure the goal is to get 2 weekday and 2 weekend days.
  * Food intake：Photographic and food weighing methods to record food intake for two random days before intervention.

Exercise intervention:

* Exercise period: 12 weeks
* Exercise frequency: 5 times a week
* Exercise modality: Under the supervision of the researcher, participants will run on a treadmill
* Exercise intensity: 60% of VO2max (running speed and treadmill incline determined based on VO2max)
* Exercise energy expenditure: 150Kcal (Weeks 1-4, gradually increase to 150Kcal in the first two weeks), 250Kcal (Weeks 5-8), 350Kcal (Weeks 9-12), increasing monthly.
* Weight monitoring: Record participants' body weight changes during exercise without informing participants of the changes.
* Heart rate monitoring: Participants need to wear a 24-hour heart rate recorder every months during exercise intervention to monitor heart rate changes.
* VO2max testing: Due to physiological and psychological adaptability,exercise will increase VO2max. To ensure consistent exercise intensity and energy expenditure, VO2max testing will be conducted every four weeks to adjust the speed and duration of exercise for the following each four weeks.
* Blood sample collection: Fasting blood will be collected every four weeks.

Immediately measurement after 12 weeks'exercise intervention (same as pre-exercise intervention baseline measurement):

* Anthropometric measurements: body weight, height, and body composition.
* Metabolic measurements: blood pressure, glucose, heart rate, energy expenditure, and cardiovascular function.
* Sample collection: Serum, feces, and urine.
* Behaviour monitor: physical activity and food intake.

Follow-up measurement 8 weeks post-completion of the exercise intervention (same as pre-exercise intervention baseline measurement):

* Anthropometric measurements: body weight, height, and body composition
* Metabolic measurements: blood pressure, glucose, heart rate, energy expenditure, and cardiovascular function
* Sample collection: Serum, feces, and urine
* Behaviour monitor: physical activity and food intake.

Eligibility Criteria:
Inclusion Criteria:

* Sedentary individuals
* BMI ≥ 18.5 kg/m2

Exclusion Criteria:

* Individuals who have undergone major surgery in the past 6 months (excluding tooth extraction);
* Individuals on long-term medication;
* Individuals with metabolic and cardiovascular diseases such as diabetes, hypoglycemia, and hypertension;
* Individuals with exercise-related injuries, including joint diseases and fractures;
* Individuals diagnosed with infectious diseases such as HIV, tuberculosis, malaria, etc.;
* Individuals with mental and neurological disorders including anorexia nervosa;
* Individuals who have attempted weight loss or gain through various methods in the past three months;
* Individuals in preconception, pregnancy, and lactation periods;
* Individuals with autism and those with metal implants in their bodies.