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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-A01169-48 | Other Identifier | ID-RCB number, ANSM | |
| B91413-80 | Other Identifier | AFSSAPS | |
| PHRC 2009/API | Other Identifier | DHOS |
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White adipose tissue-related diseases spread from excess (obesity) to lack (lipoatrophies) through aberrant distribution (lipodystrophies), these 3 different disorders being paradoxically able to induce a metabolic insulin resistance syndrome. The respective part of quantitative and qualitative anomalies of adipose tissue, gluco- and lipo-toxicity, liver and muscle insulin resistance, low-grade fat inflammation and immune alterations are not perfectly understood in the metabolic syndrome yet. Therefore, the aim of this study is to assess different cytokines, especially interleukin 7, and metabolic parameters as well as fat mass distribution with DEXA and RMN, in different models of fat distribution, including normal-weight, obese and lipodystrophic patients. A plasma serum, gene and adipose tissue bank will be constituted at the same time to improve our knowledge in disorders linking fat mass, insulin resistance and immunity, especially in lipodystrophies, a rare monogenic model of insulin resistance.
Rational: In reason of its ability to store fatty acids and to secrete numerous pro-inflammatory cytokines, the adipocyte appears as a key cell in the regulation of energy metabolism and immune response. Moreover, it has been recently shown that adipocytes play a role in the recruitment of cells involved in innate and adaptive immunity in adipose tissue.
White adipose tissue-related diseases are numerous, spreading from excess (obesity) to a complete (lipoatrophies) or partial lack (lipodystrophies), these 3 different disorders being paradoxically able to induce a metabolic insulin resistance syndrome.
Among the involved cytokines, interleukin-7 (IL-7), mostly known for its immune functions, also participates to the quantitative and qualitative balance of fat mass. Thus, IL-7 over-expression in an animal model induces a lipodystrophic syndrome with insulin resistance whereas in humans, a preliminary study shows that LMNA-linked lipodystrophies are associated with an increase of blood IL-7 levels. IL-7 also participates to reactivation of autoimmunity in patients suffering from auto-immune type 1 after islet transplantation.
Therefore, the aim of this study is to assess different cytokines, especially interleukin 7, and metabolic parameters levels as well as fat mass distribution, in different models of fat distribution, including normal-weighed, obese and lipodystrophic patients. A plasma serum, gene and tissue bank will be constituted in order to improve our knowledge in disorders linking fat mass, insulin resistance and immunity, especially in lipodystrophies, a rare monogenic model of insulin resistance.
Patients: The included patients correspond to subjects of either normal body weight, or obese, or suffering from lipodystrophic syndrome, whatever their type 2 diabetes status.
Methods: Blood IL-7 levels, other immune and/or pro-inflammatory cytokines, lymphocytes immuno-phenotype as well as metabolic parameters will be characterized. Fat mass will be assessed with non-invasive methods (DEXA and RMN). A plasma, serum and gene bank will be constituted. As well as an adipose tissue bank in patients who will have a surgery (especially plastic surgery in lipodystrophic patients), in order to cryo-preserve it and to define the inflammatory status of this tissue thanks to histological and molecular analysis.
Main judgment criteria: The main judgment criteria will be IL-7 blood levels in the different groups according to fat mass and metabolic parameters. The hypothesis is that in humans the quantitative and /or qualitative disturbances of adipose tissue are associated with an increase of IL-7 levels and the development of insulin-resistance.
Awaited results and possible implications: this study will allow to better delineate the immune and inflammatory component associated with alterations of fat mass distribution and glucose metabolism. Our approach combining clinical investigation and ex vivo and laboratory analysis is original and should allow to better understand the cellular mechanisms responsible for the inflammatory process originated in white adipose tissue and accompanying the disorders of this tissue- more especially lipodystrophic syndromes - opening new therapeutic perspectives in common human diseases (obesity, diabetes) on the one hand, and a rare disease (lipodystrophy) on the other hand.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| normal | Patients with no overweight and no type 2 diabetes | ||
| lipodystrophy | patients with a lipodystrophy, most are diabetics | ||
| obese non diabetics | Patients with obesity (BMI <30kg/m2), without diabetes | ||
| obese diabetics | Patients with obesity (BMI <30 kg/m2), with diabetes |
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| Measure | Description | Time Frame |
|---|---|---|
| Measure of blood Interleukin 7 | 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| measure of blood Interleukins 2 | 1 day | |
| measure of blood interleukin 9 | 1 day | |
| measure of blood Interleukin 15 |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with lipodystrophy : Endocrinology Departments of Lille , Amiens, Caen, Rouen and Reims University hospitals.
Obese (diabetics and non diabetics) and normal weight patients : Endocrinology - Metabolism, Endocrine Surgery and Nutrition Departments, Lille University Hospital
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| Name | Affiliation | Role |
|---|---|---|
| marie christine VANTYGHEM, pHd | University Hospital, Lille | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amiens University Hospital | Amiens | 80054 | France | |||
| Caen University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34187516 | Result | Lemaitre M, Chevalier B, Jannin A, Le Mapihan K, Boury S, Lion G, Labalette M, Vantyghem MC. Metabolic and immunological phenotype of rare lipomatoses: Dercum's disease and Roch-Leri mesosomatic lipomatosis. Orphanet J Rare Dis. 2021 Jun 29;16(1):290. doi: 10.1186/s13023-021-01920-3. |
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| ID | Term |
|---|---|
| D008060 | Lipodystrophy |
| D009765 | Obesity |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D012875 | Skin Diseases, Metabolic |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D052439 | Lipid Metabolism Disorders |
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Wholeblood and tissue bank
| 1 day |
| measure of blood TNF | 1 day |
| measure of blood IL-1 | 1 day |
| measure of blood IL-6 | 1 day |
| measure of blood IL-8 | 1 day |
| measure of blood IL-10 | 1 day |
| measure of blood IL-18 | 1 day |
| measure of blood leptin | 1 day |
| measure of blood adiponectin | 1 day |
| Blood count of monocytes/macrophages | 1 day |
| Blood count of dendritic cells | 1 day |
| Count of blood lymphocytes T | 1 day |
| Caen |
| 14032 |
| France |
| Lille University Hospital | Lille | 59037 | France |
| Reims University Hospital | Reims | 51092 | France |
| Rouen University Hospital | Rouen | 76031 | France |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D004700 | Endocrine System Diseases |