Adipose Tissue Pre and Post Bariatric Surgery

Study Overview
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Brief Summary
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Published data suggest that inflammation and fibrosis of adipose tissue could be factors favoring the development of insulin resistance in obese individuals and that a decrease in the activity of the AMP-activity kinase protein (AMPK) could lead to these dysfunctions. However, very few data are available in humans. There is also growing interest in persistent organic pollutants (POPs) as a cardiometabolic and type 2 diabetes (T2D) risk factor. There is some evidence to suggest that POPs directly contribute to lipid metabolism dysfunction and insulin resistance. Additionally, POPs are stocked in adipose tissue. The accumulation of POPs in adipose tissue therefore limits their bioavailability to other organs, thus reducing their systemic toxicity. It has been observed that a large amplitude weight loss leads to a significant increase in POPs in the blood. The goal of this project is to identify adipose tissue factors/dysfunctions that contribute to insulin resistance and type 2 diabetes associated with obesity in humans and thus raise avenues for screening and treatment of these metabolic complications. More specifically, the objectives are: To study the relationship between AMPK, fibrosis and inflammation of adipose tissue and their role in the development of insulin resistance and T2D associated with obesity; To examine the relationship between POPs and the cardiometabolic profile.

Official Title
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Evaluation of Adipose Tissue Pre and Post Bariatric Surgery

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Bariatric surgery
* Other: Blood sampling
* Other: Blood pressure
* Other: Anthropometric measurements
* Other: Body composition
* Other: Resting metabolic rate
* Other: Food intake
* Procedure: Adipose tissue biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Awaiting bariatric surgery BMI ≥ 35 kg/m2 without cardiometabolic complications or ≥ 30 kg/m2 if presence of type 2 diabetes or hypertension ≥ 18 years old Non smoker Sedentary (less than 3 hours of regular physical activity per week) Exclusion Criteria: Type 1 diabetes Acute event in the last 3 months (myocardial infarction, cerebrovascular hemorrhage or transient cerebral ischemia, unstable angina, peripheral vascular disease, revascularization or angioplasty, recent hospitalization for more than 4 days) Infection in the last month (fever, antibiotics treatment) Cancer in the last 3 years Chronic inflammatory disease Pharmacologic treatment (any medication affecting glucose metabolism (except those for diabetes), hypotensive medication unless stable dose for at least 1 month, lipid-lowering medication unless stable dose for at least 1 month) Uncontrolled disease of pituitary or thyroid gland Bleeding disorders Alcohol or drug abuses Claustrophobia

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Obese with type 2 diabetes<br> | Procedure: Bariatric surgery<br>* Sleeve gastrectomy<br>Other: Blood sampling<br>* Blood samples will be collected to measure glucose, insulin, albumin, uric acid, HbA1c, lipids, hepatic enzymes, TSH, hs-CRP, complete blood cell counts and persistant organic pollutants<br>Other: Blood pressure<br>* Systolic and diastolic blood pressure will be measured.<br>Other: Anthropometric measurements<br>* Body weight, height and waist circumference will be measured.<br>Other: Body composition<br>* Body composition will be evaluated by dual-energy X-ray absorptiometry.<br>Other: Resting metabolic rate<br>* Resting metabolic rate will be measured by indirect calorimetry.<br>Other: Food intake<br>* Food intake, energy intake and food quality will be evaluated using the food frequence questionnaire.<br>Procedure: Adipose tissue biopsy<br>* A sample of 3-5g of adipose tissue will be collected under local anesthesia by needle aspiration in the periumbilical region.<br>|
| Obese insulin-sensitive<br> | Procedure: Bariatric surgery<br>* Sleeve gastrectomy<br>Other: Blood sampling<br>* Blood samples will be collected to measure glucose, insulin, albumin, uric acid, HbA1c, lipids, hepatic enzymes, TSH, hs-CRP, complete blood cell counts and persistant organic pollutants<br>Other: Blood pressure<br>* Systolic and diastolic blood pressure will be measured.<br>Other: Anthropometric measurements<br>* Body weight, height and waist circumference will be measured.<br>Other: Body composition<br>* Body composition will be evaluated by dual-energy X-ray absorptiometry.<br>Other: Resting metabolic rate<br>* Resting metabolic rate will be measured by indirect calorimetry.<br>Other: Food intake<br>* Food intake, energy intake and food quality will be evaluated using the food frequence questionnaire.<br>Procedure: Adipose tissue biopsy<br>* A sample of 3-5g of adipose tissue will be collected under local anesthesia by needle aspiration in the periumbilical region.<br>|
| Obese insulin-resistant<br> | Procedure: Bariatric surgery<br>* Sleeve gastrectomy<br>Other: Blood sampling<br>* Blood samples will be collected to measure glucose, insulin, albumin, uric acid, HbA1c, lipids, hepatic enzymes, TSH, hs-CRP, complete blood cell counts and persistant organic pollutants<br>Other: Blood pressure<br>* Systolic and diastolic blood pressure will be measured.<br>Other: Anthropometric measurements<br>* Body weight, height and waist circumference will be measured.<br>Other: Body composition<br>* Body composition will be evaluated by dual-energy X-ray absorptiometry.<br>Other: Resting metabolic rate<br>* Resting metabolic rate will be measured by indirect calorimetry.<br>Other: Food intake<br>* Food intake, energy intake and food quality will be evaluated using the food frequence questionnaire.<br>Procedure: Adipose tissue biopsy<br>* A sample of 3-5g of adipose tissue will be collected under local anesthesia by needle aspiration in the periumbilical region.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipose tissue fibrosis using qRT-PCR, immunoblotting, histochemistry and immunohistochemistry |  | Before bariatric surgery | 
| Adipose tissue fibrosis using qRT-PCR, immunoblotting, histochemistry and immunohistochemistry |  | 6 months after bariatric surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calory intake |  | Before bariatric surgery | 
| Calory intake |  | 3 months after bariatric surgery | 
| Calory intake |  | 6 months after bariatric surgery | 
| Food quality using the Food Frequency Questionnaire |  | Before bariatric surgery | 
| Food quality using the Food Frequency Questionnaire |  | 3 months after bariatric surgery | 
| Food quality using the Food Frequency Questionnaire |  | 6 months after bariatric surgery | 
| Persistant organic pollutants measured by high-resolution chromatography combined with high-resolution mass spectrometry |  | Before bariatric surgery | 
| Persistant organic pollutants measured by high-resolution chromatography combined with high-resolution mass spectrometry |  | 3 months after bariatric surgery | 
| Persistant organic pollutants measured by high-resolution chromatography combined with high-resolution mass spectrometry |  | 6 months after bariatric surgery | 
| AMP-activated protein kinase |  | Before bariatric surgery | 
| AMP-activated protein kinase |  | 3 months after bariatric surgery | 
| AMP-activated protein kinase |  | 6 months after bariatric surgery | 
| Inflammation in adipose tissue using qRT-PCR, immunoblotting and immunohistochemistry |  | Before bariatric surgery | 
| Inflammation in adipose tissue using qRT-PCR, immunoblotting and immunohistochemistry |  | 3 months after bariatric surgery | 
| Inflammation in adipose tissue using qRT-PCR, immunoblotting and immunohistochemistry |  | 6 months after bariatric surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bariatric surgery, Persistant organic pollutants, Type 2 diabetes