Effect of Exercise and Training on Fat Oxidation During Overfeeding - the FeedEX Study

Study Overview
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Brief Summary
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Rationale: Body weight is not well regulated in all individuals. In an obesogenic environment, where overeating is common, some individuals are more prone to weight gain and therefore overweight than others. Yet, the reasons behind this are unclear. Resistant individuals often have higher physical activity levels (PALs). It seems that - at higher levels of physical activity and therefore energy expenditure - satiety signals are more precisely regulated, making one better at matching energy intake with expenditure. In other words, active people may not overeat where sedentary people would. However, this does not explain the differences in weight gain observed when subjects all have to overeat (imposed overfeeding). It could be that active people are better able to cope metabolically with the extra calories because of already higher levels of carbohydrate and fat oxidation compared to their inactive counterparts. Objectives: 1/ To study the effects of overfeeding (normal diet composition) on substrate balance and oxidation and more specifically fat balance and oxidation; 2/ to study the effects of exercise and training on fat oxidation during overfeeding (normal diet composition). Study design: This controlled intervention study will follow a cross-over design. Each subject will spend 5 nights and 4 days in a respiration chamber on two occasions, separated by a 10-week training period.

Official Title
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Effects of Short-term Overfeeding With or Without Exercise on 24-hour Fat Oxidation and Fat Balance Before and After 10 Weeks of Training - The FeedEX Study

Conditions
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Overfeeding and Exercise

Intervention / Treatment
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* Other: overfeeding + exercise pre-training
* Behavioral: fitness training
* Other: overfeeding + exercise post-training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasians Male Healthy 18-30 years BMI 21-27.5 kg.m-2 Sedentary lifestyle: the following serve as (non-strict) guidelines: Low category of activity according to the short version of the International Physical Activity Questionnaire (IPAQ); VO2max (ml.kg-1.min-1) below: 45 - AGE (yrs) / 3 corresponding to a fitness category below fair (i.e. poor or very poor) as defined by Schvartz and Reibold. For example for an 18 year-old male, VO2max below 39 ml.kg-1.min-1. Stable body weight (<5% change in the last 6 months) Exclusion Criteria: Following a (weight-loss) diet Using medications Smoking Consuming more than 3 units of alcohol per day Diagnosed with any chronic diseases known to affect energy metabolism (intake/expenditure) such as diabetes, cardiovascular disease, cancer, or thyroid disease. Trained or regularly physically active (according to the IPAQ)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Overfeeding + exercise pre/post training<br>overfeeding + exercise pre-training: day1 energy balance; day2 and day3: energy intake equals 1.25 times day 2 and day 3 energy expenditure respectively, no exercise; day4: 3 cycling bouts to expend 0.25 times day3 energy expenditure + energy intake equals 1.25 times day4 energy expenditure - before training period. fitness training: 10-week training period (3 times per week at a gym, 30-45 minutes cardio training and 15-30 minutes strength training). overfeeding + exercise post-training: day1 energy balance; day2 and day3: energy intake equals 1.25 times day 2 and day 3 energy expenditure respectively, no exercise; day4: 3 cycling bouts to expend 0.25 times day3 energy expenditure + energy intake equals 1.25 times day4 energy expenditure - after training period. | Other: overfeeding + exercise pre-training<br> <br> Behavioral: fitness training<br> <br> Other: overfeeding + exercise post-training<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour fat balance with overfeeding after training | Day3 24-hour fat balance (calculated as the difference between metabolisable fat intake and fat oxidation measured by indirect calorimetry in respiration chamber) after training compared to baseline (=before training) | Baseline and 3 months | 
| Change in 24-hour fat balance with overfeeding and exercise after training | Day4 24-hour fat balance (calculated as the difference between metabolisable fat intake and fat oxidation measured by indirect calorimetry in respiration chamber) after training compared to baseline (=before training) | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour fat oxidation with overfeeding and exercise in inactive men | Fat oxidation measured by indirect calorimetry in respiration chamber on day 4 compared to day 3 at baseline | Day 3 and day 4 (baseline stay in respiration chamber) | 
| Change in 24-hour carbohydrate oxidation with overfeeding and exercise in inactive men | Carbohydrate oxidation measured by indirect calorimetry in respiration chamber on day 4 compared to day 3 at baseline | Day 3 and day 4 (baseline stay in respiration chamber) | 
| Change in 24-hour fat balance with overfeeding and exercise in inactive men | Fat balance (calculated as the difference between metabolisable fat intake and fat oxidation) on day 4 compared to day 3 at baseline | Day 3 and day 4 (baseline stay in respiration chamber) | 
| Change in 24-hour fat oxidation with overfeeding and exercise in active men | Fat oxidation measured by indirect calorimetry in respiration chamber on day 4 compared to day 3 after the training period | Day 3 and day 4 (stay in respiration chamber at 3 months) | 
| Change in 24-hour carbohydrate oxidation with overfeeding and exercise in active men | Carbohydrate oxidation measured by indirect calorimetry in respiration chamber on day 4 compared to day 3 after the training period | Day 3 and day 4 (stay in respiration chamber at 3 months) | 
| Change in 24-hour fat balance with overfeeding and exercise in active men | Fat balance (calculated as the difference between metabolisable fat intake and fat oxidation) on day 4 compared to day 3 after the training period | Day 3 and day 4 (stay in respiration chamber at 3 months) | 
| Change in 24-hour carbohydrate oxidation with overfeeding after training | Day3 24-hour carbohydrate oxidation measured by indirect calorimetry in respiration chamber after training compared to baseline (=before training) | Baseline and 3 months | 
| Change in 24-hour carbohydrate oxidation with overfeeding and exercise after training | Day4 24-hour carbohydrate oxidation measured by indirect calorimetry in respiration chamber after training compared to baseline (=before training) | Baseline and 3 months | 
| Change in fat oxidation after training assessed in energy balance |  | Baseline and 3 months | 
| Change in carbohydrate oxidation after training assessed in energy balance |  | Baseline and 3 months | 
| Energy expenditure with overfeeding in inactive men | Energy expenditure measured by indirect calorimetry during a 4-day stay in respiration chamber, with overfeeding on days 2 to 4. | 4 days at baseline | 
| Energy expenditure with overfeeding in active men | Energy expenditure measured by indirect calorimetry during a 4-day stay in respiration chamber, with overfeeding on days 2 to 4, after a 10-week fitness training. | 4 days at 3 months | 
| Insulin sensitivity | Based on glucose and insulin plasma concentrations from oral glucose tolerance test, where blood is collected in fasted state at t=0, 30, 60, 90 and 120min after a glucose drink is ingested) | Baseline, 2 weeks (pre-training), 3 months (post-training) | 
| adipocyte size | Fat biopsy taken these time points | Baseline, 2 weeks (pre-training), 3 months (post-training) | 
| Genes involved in lipid metabolism | Using fat biopsies: analysis of genes involved in the lipolytic pathway [ATGL (PNPLA2), HSL (S660/565/563), CGI-58, G0S2, PLIN1, AQP7, GK], in insulin signaling/glucose metabolism [GLUT4, IRS1/IRS2, AKT, pAKT (S473), pIRS1 (S1101)], in fatty acid metabolism [CD36, FABP4 (aP2), FASN, CPT1a/1b, CPT2, ACADL/ACADVL/ACADS/ACADM, ACOX1, OXPHOS (complex I-V), PPAR(α/βδ/γ), PGC1a, PGC1b, SIRT1, AMPK (pAMPK)], and in DAG/ceramide metabolism [DGAT 1/2, GPAT1/GPAM, PLC, SPTLC1 and SPTLC2, CERK, ASAH1 and ASAH2 | Baseline, 2 weeks (pre-training), 3 months (post-training) | 
| Change in body composition | Measured using body weight, underwater weighing and deuterium dilution, before and after the fitness training | Baseline and 3 months | 
| Change in cardiorespiratory fitness | Cardiorespiratory fitness estimated as the maximal oxygen uptake (VO2max) assessed using an incremental test on a bicycle ergometer | Baseline, after 6-7 weeks of training and 3 months | 
| Change in energy expenditure in free-living conditions | Energy expenditure measured over 14 days using doubly-labeled water and two accelerometers (TracmorD and Actigraph GT3X) | Baseline and 3 months | 
| Validity of Actigraph GT3X accelerometer | The Actigraph GT3X accelerometer is worn by each subject twice for 14 days and will be validated against the doubly labeled water technique and compared to the tracmorD accelerometer | Two 14-day periods (baseline and 3 months) |