Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophy, Diabetes and Obesity

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.