Study of the Role of PCSK9 and FXR in the Physiopathology of the Joint Dyslipidemia Associated to the Human Immunoresistance

Study Overview
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Brief Summary
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Experimental results are strongly suggesting that PCSK9 and FXR could occur in the physiopathology of human joined dyslipidemia. But no data in the literature can validate the potential role of these two genes in the lipidic and glucidic metabolism control in physiopathological situations. This protocol is based on the hypothesis that the expression levels of PCSK 9 and FXR are modified for some patients suffering from insulin resistance and dyslipidemia.

Official Title
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Study of the Role of PCSK9 and FXR in the Physiopathology of the Joint Dyslipidemia Associated to the Human Immunoresistance

Conditions
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Obesity

Intervention / Treatment
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* Procedure: biopsy of muscle, of liver, and of adipose tissue
* Procedure: clamp euglycemic - hyperglycemic
* Behavioral: diet
* Other: biopsies for biological and genetic analyses


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: corporal mass index > 40 kg/m² or > 35 kg/m² associated to a co-morbidity resistant to a diet bariatric surgery planned no lipid-lowering drugs during 4 weeks before surgery no treatment by metformin during 4 weeks before surgery no treatment by glitazones during 8 weeks before surgery age of the patient between 18 and 65 years consent form signed patient with social insurance Exclusion Criteria: age inferior to 18 years women pregnant coagulation troubles surgery contraindicated Chronic hepatitis B or C active VIH infected other chronic hepatic disease patient with dyslipidemia under lipid-lowering drugs in secondary prevention of a cardiovascular pathology Type 2 diabetes under insulinosensitivator treatments

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Non diabetic non dyslipidemic patient | Procedure: biopsy of muscle, of liver, and of adipose tissue<br>* biopsy of muscle, of liver, and of adipose tissue<br>Procedure: clamp euglycemic - hyperglycemic<br>* clamp euglycemic-hyperglycemic<br>Behavioral: diet<br>* diet<br>Other: biopsies for biological and genetic analyses<br>* biopsies for biological and genetic analyses<br>|
| Experimental: 2<br>Patient with metabolic syndrome | Procedure: biopsy of muscle, of liver, and of adipose tissue<br>* biopsy of muscle, of liver, and of adipose tissue<br>Procedure: clamp euglycemic - hyperglycemic<br>* clamp euglycemic-hyperglycemic<br>Behavioral: diet<br>* diet<br>Other: biopsies for biological and genetic analyses<br>* biopsies for biological and genetic analyses<br>|
| Experimental: 3<br>Patients with type II diabetes | Procedure: biopsy of muscle, of liver, and of adipose tissue<br>* biopsy of muscle, of liver, and of adipose tissue<br>Procedure: clamp euglycemic - hyperglycemic<br>* clamp euglycemic-hyperglycemic<br>Behavioral: diet<br>* diet<br>Other: biopsies for biological and genetic analyses<br>* biopsies for biological and genetic analyses<br>|
| Experimental: 4<br>Patient with a single lipidic anomaly | Procedure: biopsy of muscle, of liver, and of adipose tissue<br>* biopsy of muscle, of liver, and of adipose tissue<br>Procedure: clamp euglycemic - hyperglycemic<br>* clamp euglycemic-hyperglycemic<br>Behavioral: diet<br>* diet<br>Other: biopsies for biological and genetic analyses<br>* biopsies for biological and genetic analyses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the relationship between the expression levels of PCSK9 and FXR in the liver, adipose tissue and muscle and the different components of the insulin resistance syndrome obese patients submitted to bariatric surgery |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between the levels of hepatic expression of PCSK9 and FXR and the degree of NASH in these patients. - Search for mutations and polymorphisms in the gene PCSK9 and FXR and their promoter regions |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bariatric surgery planned