Progressive Metabolic Adaptations to Low Intensity Exercise Training and Weight Loss

Study Overview
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Brief Summary
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the investigators first aim is to determine the effect of low intensity exercise (without weight loss) on insulin sensitivity, muscle lipid metabolism, and factors regulating these processes in skeletal muscle after 1 day, 2 wks, 12 wks of training, and again after 3 days without exercise in obese adults. the investigators second aim is to determine the effect of combining low intensity exercise training with 10% weight loss on insulin sensitivity, muscle lipid metabolism, and factors regulating these processes in skeletal muscle. Although a single 40 minute session of exercise at a low exercise intensity will not improve insulin sensitivity, the investigators anticipate adaptations after two weeks of exercise training (6 session/wk; 12 session total) will improve insulin sensitivity and be accompanied by a reduction in fatty acid intermediates and a reduction in markers for pro-inflammatory activation in muscle. the investigators anticipate changes in insulin sensitivity, fatty acid partitioning, and pro-inflammatory markers the day after the last session of a 12 wk training program (without weight-loss) will be similar to that measured after 2 weeks of training. the investigators anticipate insulin sensitivity, accumulation of fatty acid intermediates, and pro-inflammatory activation will be markedly improved after 10% weight loss when measured the day after exercise. the investigators would expect the improvements in Insulin sensitivity, accumulation of fatty acid intermediates, and markers of inflammatory stress will be significantly attenuated when measured 3 days after the most recent exercise session, but beneficial effects of 10% weight loss on these metabolic endpoints will persist when compared with before weight loss.

Conditions
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Obesity

Intervention / Treatment
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* Other: Exercise Training
* Other: Weight Loss with continued Exercise Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: body mass index [BMI]: 30-45 kg/m2; All women must be pre-menopausal; Non-exerciser (no regularly planned exercise/physical activity) Exclusion Criteria: Hematocrit ≤ 34%; Fasting plasma glucose concentration ≥ 125 mg/dL; Weight instability ≥ ±5 lbs in past month; Taking medications known to affect lipid and/or glucose metabolism; evidence and/or history of cardiovascular or frank metabolic diseases; pregnancy or actively breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Other: Exercise Training with Weight Loss<br>During the first 12 weeks of the study, subjects will adhere to an exercise training program while maintaining their original body weight. The exercise training program will entail the following: 40min/session,  50% of their maximal aerobic capacity (approximately 100-110 beats per min), 5-6 days/week After the first 12 weeks in the study, subjects will continue with the same exercise program, but then they will be placed on a reduced calorie diet until they lose exactly 10% of their original body weight | Other: Exercise Training<br>* During the first 12 weeks of the study, subjects will adhere to an exercise training program while maintaining their original body weight. The exercise training program will entail the following: 40min/session,  50% of their maximal aerobic capacity (approximately 100-110 beats per min), 5-6 days/week<br>Other: Weight Loss with continued Exercise Training<br>* After the first 12 weeks in the study, subjects will continue with the same exercise program, but then they will be placed on a reduced calorie diet until they lose exactly 10% of their original body weight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | A hyperinsulinemic-euglycemic clamp will be used to assess peripheral insulin sensitivity | 2-3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting Metabolic Rate |  | 20-30 min | 
| Meal Tolerance Test |  | 2-3h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin Sensitivity, Exercise Training, Weight Loss, Fat Metabolism