Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophy, Diabetes and Obesity
Condition: Lipodystrophy; Obesity; Type 2 Diabetes
MeSH terms: Lipodystrophy; Obesity; Insulin Resistance
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        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
      
Biospecimen description: 
      Wholeblood and tissue bank
    
Keywords: Interleukin 7; adipose tissue