Translational Study Using Human Abdominal Adipose Tissue Biopsies to Investigate the Role of Cannabinoid Receptor 1 (CB1) in Controlling Endocannabinoid and Adipokine Secretion

Study Overview
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Brief Summary
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Abdominal obesity and type 2 diabetes are associated with the hyperactivation of the endocannabinoid system. Several animal and human studies indicate that circulating endocannabinoid (EC) levels are correlated with body fat. Thus, adipose tissue, which possesses the enzymatic machinery for the synthesis of ECs, could be the main producer of plasma ECs. Today, it is clearly established that stimulation of the endocannabinoid system, via activation of cannabinoid receptor 1 (CB1s) located in the brain, leads to increased food intake and weight gain. Moreover, peripheral CB1s present in organs such as the liver, muscles and adipose tissue are involved in the establishment of metabolic deregulations linked to obesity (steatosis, insulin resistance, dyslipidemia). Thus, ECs produced by adipose tissue could play a key role in the regulation of carbohydrate-lipid homeostasis through their autocrine or paracrine actions by activating central and peripheral CB1s. Therefore, the objective of this study is to: clarify whether obesity, associated or not with diabetes, leads to an overproduction of ECs (specifying which ones) by visceral or subcutaneous adipose tissue to determine whether blocking CB1s with new peripherally acting antagonists can lead to a reduction in the production of ECs by adipose tissue. This study will also provide an opportunity to evaluate the production of adipokines and cytokines involved in the control of energy homeostasis under the different experimental conditions.

Official Title
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Translational Study Using Human Abdominal Adipose Tissue Biopsies to Investigate the Role of Cannabinoid Receptor 1 (CB1) in Controlling Endocannabinoid and Adipokine Secretion

Conditions
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Diabete Type 2, Abdominal Obesity

Intervention / Treatment
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* Procedure: Sampling of adipose tissue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Controls: men or post-menopausal women aged between 18 and 80 gave oral consent to undergo visceral surgery Non-diabetic obese subjects: men or post-menopausal women aged between 18 and 80 BMI > 30 gave oral consent to undergo visceral surgery Obese diabetic subjects: men or post-menopausal women aged between 18 and 80 type 2 diabetic not treated with Insulin or GLP-1 agonist BMI > 30 gave oral consent to undergo visceral surgery Exclusion Criteria: Controls: Person not covered by national health insurance. BMI > 30 diabetes chronic inflammatory disease cancer undergoing chemotherapy or chemotherapy less than a year old digestive cancer with recent weight loss (≥10%) and/or malnutrition known metastatic cancer cancer undergoing long-term hormonal treatment protected adult Non-diabetic obese subjects: Person not covered by national health insurance diabetes chronic inflammatory disease cancer undergoing chemotherapy or chemotherapy less than a year old digestive cancer with recent weight loss (≥10%) and/or malnutrition known metastatic cancer cancer undergoing long-term hormonal treatment protected adult Obese diabetic subjects: Person not covered by national health insurance chronic inflammatory disease cancer undergoing chemotherapy or chemotherapy less than a year old digestive cancer with recent weight loss (≥10%) and/or malnutrition known metastatic cancer cancer undergoing long-term hormonal treatment type 1 diabetes secondary diabetes protected adult

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-diabetic obese<br> | Procedure: Sampling of adipose tissue<br>* Removal of less than 1 cm3 of adipose tissue during visceral surgery<br>|
| Experimental: Diabetic obese<br> | Procedure: Sampling of adipose tissue<br>* Removal of less than 1 cm3 of adipose tissue during visceral surgery<br>|
| Active Comparator: Witnesses<br> | Procedure: Sampling of adipose tissue<br>* Removal of less than 1 cm3 of adipose tissue during visceral surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics of the appearance of endocannabinoids produced by visceral adipose tissue explants in culture medium estimated by the area under the curve in obese subjects and in controls. | The assay will be performed using a technique of liquide chromatography coupled to a mass spectrometer. | 12 hours |