Metabolically Normal and Metabolically Abnormal Obesity

Study Overview
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Brief Summary
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The purpose of this study is to learn more about why some obese persons are resistant to developing obesity-related metabolic diseases (such as diabetes and cardiovascular disease), while others are prone to developing these conditions. We will do this by studying obese persons before and after a 5% body weight gain. Subjects will be asked to increase their current diet for a period of 8-12 weeks in order to increase their current body weight by 5%. Each will then be asked to maintain this weight increase for 3 weeks. We will monitor subjects throughout this time period with weekly medical evaluations. At the completion of the study, we will provide each subject with a 6-month weight loss program.

Official Title
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Metabolically Normal and Metabolically Abnormal Obesity

Conditions
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Obesity, Metabolic Syndrome

Intervention / Treatment
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* Behavioral: overfeeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese subjects (BMI 30.0 - 39.9 kg/m2) Sedentary subjects (exercise less than 1 hr/wk) Exclusion Criteria: Pregnant or lactating women Michigan Alcohol Screening Test score ≥4 Active or previous history of liver disease Active or previous history of diabetes history of alcohol abuse, or currently consuming ≥20 g alcohol/day Severe hypertriglyceridemia (>300 mg/dL) Smoke tobacco Take medication that might confound the study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metabolically Normal<br>Subjects in this group are metabolically normal. They have low liver fat defined as less than five percent as determined by magnetic resonance spectroscopy. Intervention: Subjects will begin an 8-12 week high-calorie diet intervention. They will eat an additional 1000 kcal/day for two to three months, until a moderate, approximately 5% weight gain is achieved. The recommended dietary energy intake will be 1000 kcal/d more than the subject's baseline resting energy expenditure. An individualized diet plan will be developed for each subject by the study dietitian based on estimated energy requirements, and the subject's food preferences and dietary habits. | Behavioral: overfeeding<br>* Subjects will begin an 8-12 week high-calorie diet intervention. They will eat an additional 1000 kcal/day for two to three months, until a moderate, approximately 5% weight gain is achieved. The recommended dietary energy intake will be 1000 kcal/d more than the subject's baseline resting energy expenditure. An individualized diet plan will be developed for each subject by the study dietitian based on estimated energy requirements, and the subject's food preferences and dietary habits.<br>* Other names: directed weight gain;|
| Experimental: Metabolically Abnormal<br>Subjects in this group are metabolically abnormal. They have high liver fat defined as at least ten percent as determined by magnetic resonance spectroscopy. Intervention: Subjects will begin an 8-12 week high-calorie diet intervention. They will eat an additional 1000 kcal/day for two to three months, until a moderate, approximately 5% weight gain is achieved. The recommended dietary energy intake will be 1000 kcal/d more than the subject's baseline resting energy expenditure. An individualized diet plan will be developed for each subject by the study dietitian based on estimated energy requirements, and the subject's food preferences and dietary habits. | Behavioral: overfeeding<br>* Subjects will begin an 8-12 week high-calorie diet intervention. They will eat an additional 1000 kcal/day for two to three months, until a moderate, approximately 5% weight gain is achieved. The recommended dietary energy intake will be 1000 kcal/d more than the subject's baseline resting energy expenditure. An individualized diet plan will be developed for each subject by the study dietitian based on estimated energy requirements, and the subject's food preferences and dietary habits.<br>* Other names: directed weight gain;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Intrahepatic Triglyceride |  | an average of three months, from baseline to 5% weight gain | 
| Change in de novo lipogenesis |  | an average of three months, from baseline to 5% weight gain | 
| Change in VLDL kinetics |  | an average of three months, from baseline to 5% weight gain | 
| Change in hepatic insulin sensitivity |  | an average of three months, from baseline to 5% weight gain | 
| Change in skeletal muscle insulin sensitivity |  | an average of three months, from baseline to 5% weight gain | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in adipose tissue insulin sensitivity |  | an average of three months, from baseline to 5% weight gain | 
| Change in CD36 concentration in skeletal muscle |  | an average of three months, from baseline to 5% weight gain | 
| change in CD36 concentration in adipose tissue |  | an average of three months, from baseline to 5% weight gain | 
| Change in cell proliferation (growth) rates in the colon |  | an average of three months, from baseline to 5% weight gain | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, metabolism, cardiovascular metabolic syndrome