Gastric Bypass and Peripheral Activity of the Endocannabinoid System

Study Overview
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Brief Summary
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The aim of the study is to precise the effect of a large amount of weight loss induced by gastric bypass on the endocannabinoid system (plasma and adipose tissue) of morbidly obese patients and to determine the influence of a gastric bypass surgery compared to a lifestyle intervention with equivalent weight loss on the endocannabinoid system

Detailed Description
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Dysregulation of the endocannabinoid system has been associated with the development of obesity, metabolic and cardiovascular disorders in both animals and humans. Obese patients, especially those with abdominal obesity, have significantly higher levels of endocannabinoids. No influence of moderate (5%) body weight loss (induced either by diet intervention or sibutramine) on the peripheral activity of the endocannabinoid system gastric bypass (GB) surgery is the most efficient treatment of obesity Hormonal pathways may participate to the weight reducing effect of the procedure.The endocannabinoid system is present in the gastrointestinal tract. In animals, sustained weight loss after GB is characterized by reduction of endocannabinoids levels. The endocannabinoid levels will be studied (baseline and after stimulation) in: Normal-weight subjects Obese subjects before and after gastric bypass surgery Obese subjects before and after a lifestyle intervention

Official Title
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Effect of Weight Loss Induced Either by Gastric Bypass or Lifestyle Intervention on the Peripheral Activity of the Endocannabinoid System

Conditions
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Obesity

Intervention / Treatment
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* Biological: Evaluation of the endocannabinoid system
* Procedure: Biopsy of visceral and peripheral adipose tissue
* Biological: Evaluation of metabolic parameters
* Behavioral: Evolution of behavioral parameters
* Behavioral: Dietician consultation
* Behavioral: Psychologist consultation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Arms 1 and 2: Age between 18 and 60 BMI > 40kg/m² or at least 30kg/m² with complication Medical follow up before surgery Patients that engaged themselves to a long medical follow up Efficient contraception Written, informed consent of each subject before the beginning of the study Arm 3: Age between 18 and 60 BMI between 18 and 25 kg/m² Stable weight over the 3 past months Restrain score <4 disinhibition <6and hunger > 4 at the TFEQ No job in the endocrinology department Written, informed consent of each subject before the beginning of the study Exclusion Criteria: Arms 1,2 and 3 No care of obesity before inclusion Incapacity of the patient to follow a medical follow up Drug or alcohol abuse Urine test result positive for THC Threaten life diseases Pregnancy, breast feeding Smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bypass gastric<br>First arm is represented by obese patients that will be studied before and after a gastric bypass. They will be studied before surgery as well as 1 month and 6 months after surgery. | Biological: Evaluation of the endocannabinoid system<br>* The evaluation of the endocannabinoid system consist in the determination of plasma concentration of the 2 main endocannabinoids (2AG and AEA) before (5 blood samples) and after (5 blood samples) after consumption of a calibrated food. As a comparator, ghrelin will be measured at the same time.<br>Procedure: Biopsy of visceral and peripheral adipose tissue<br>* The endocannabinoids will be also determined in adipose tissue. Biopsy of visceral and peripheral adipose tissue will be done during surgery and peripheral adipose tissue will be done 6 months after surgery.<br>Biological: Evaluation of metabolic parameters<br>* The evaluation of the metabolic status consist in evaluation of body composition (DEXA), determination of visceral adiposity (CT scan) and measurement of plasma lipids, glucose, insulin, leptin, adiponectin.<br>Behavioral: Evolution of behavioral parameters<br>* The behavioral evaluation will de done with different questionnaires: ORWELL 97, HAD scale, Three Factor Eating Questionnaire, Beck Depression inventory, Questionnaire of personality TCI.<br>Behavioral: Dietician consultation<br>* The evaluation of the metabolic status will also be seen by a dietician.<br>Behavioral: Psychologist consultation<br>* The behavioural evaluation will de done with a psychologist consultation<br>|
| Lifestyle intervention<br>The second group is represented by obese patients that will be studied before lifestyle intervention, 6 months after the beginning of the intervention and after a time that will allow patients to lose the same amount of weight that patients that had been through surgery had lost one month after surgery. | Biological: Evaluation of the endocannabinoid system<br>* The evaluation of the endocannabinoid system consist in the determination of plasma concentration of the 2 main endocannabinoids (2AG and AEA) before (5 blood samples) and after (5 blood samples) after consumption of a calibrated food. As a comparator, ghrelin will be measured at the same time.<br>Biological: Evaluation of metabolic parameters<br>* The evaluation of the metabolic status consist in evaluation of body composition (DEXA), determination of visceral adiposity (CT scan) and measurement of plasma lipids, glucose, insulin, leptin, adiponectin.<br>Behavioral: Evolution of behavioral parameters<br>* The behavioral evaluation will de done with different questionnaires: ORWELL 97, HAD scale, Three Factor Eating Questionnaire, Beck Depression inventory, Questionnaire of personality TCI.<br>Behavioral: Dietician consultation<br>* The evaluation of the metabolic status will also be seen by a dietician.<br>Behavioral: Psychologist consultation<br>* The behavioural evaluation will de done with a psychologist consultation<br>|
| Control subjects<br>The third group is a control group of normal weight people that will be studied at one time and after 6 months with stable weight. | Biological: Evaluation of the endocannabinoid system<br>* The evaluation of the endocannabinoid system consist in the determination of plasma concentration of the 2 main endocannabinoids (2AG and AEA) before (5 blood samples) and after (5 blood samples) after consumption of a calibrated food. As a comparator, ghrelin will be measured at the same time.<br>Biological: Evaluation of metabolic parameters<br>* The evaluation of the metabolic status consist in evaluation of body composition (DEXA), determination of visceral adiposity (CT scan) and measurement of plasma lipids, glucose, insulin, leptin, adiponectin.<br>Behavioral: Evolution of behavioral parameters<br>* The behavioral evaluation will de done with different questionnaires: ORWELL 97, HAD scale, Three Factor Eating Questionnaire, Beck Depression inventory, Questionnaire of personality TCI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasmatic endocannabinoïd concentration variation |  | Inclusion and 6 month-follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of the endocannabinoids during food exposure |  | At each visit | 
| Post prandial pic of the plasma concentration of the endocannabinoids |  | At each visit | 
| Adipose tissue concentration of the endocannabinoids |  | Inclusion and 6 month-follow up | 
| Plasma concentration of adipokines |  | At each visit | 
| Body mass index |  | At each visit | 
| Body composition |  | At each visit | 
| Insulin sensitivity |  | At each visit | 
| Area under the curve of plasma concentration of 2AG |  | Inclusion and 6 month follow-up | 
| Questionaries scores |  | At each visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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morbid obesity, bariatric surgery, lifestyle intervention, endocannabinoids system