Metabolically Normal and Metabolically Abnormal Obesity
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Metabolically Normal
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. |
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.
Other Names:
|
|
Experimental: Metabolically Abnormal
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. |
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Change in Intrahepatic Triglyceride
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
|
Change in de novo lipogenesis
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
|
Change in VLDL kinetics
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
|
Change in hepatic insulin sensitivity
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
|
Change in skeletal muscle insulin sensitivity
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Change in adipose tissue insulin sensitivity
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
|
Change in CD36 concentration in skeletal muscle
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
|
change in CD36 concentration in adipose tissue
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
|
Change in cell proliferation (growth) rates in the colon
Time Frame: an average of three months, from baseline to 5% weight gain
|
an average of three months, from baseline to 5% weight gain
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Yoshino J, Patterson BW, Klein S. Adipose Tissue CTGF Expression is Associated with Adiposity and Insulin Resistance in Humans. Obesity (Silver Spring). 2019 Jun;27(6):957-962. doi: 10.1002/oby.22463. Epub 2019 Apr 19.
- Fabbrini E, Tiemann Luecking C, Love-Gregory L, Okunade AL, Yoshino M, Fraterrigo G, Patterson BW, Klein S. Physiological Mechanisms of Weight Gain-Induced Steatosis in People With Obesity. Gastroenterology. 2016 Jan;150(1):79-81.e2. doi: 10.1053/j.gastro.2015.09.003. Epub 2015 Sep 12.
- Fabbrini E, Yoshino J, Yoshino M, Magkos F, Tiemann Luecking C, Samovski D, Fraterrigo G, Okunade AL, Patterson BW, Klein S. Metabolically normal obese people are protected from adverse effects following weight gain. J Clin Invest. 2015 Feb;125(2):787-95. doi: 10.1172/JCI78425. Epub 2015 Jan 2.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 10-0708
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