Adipocytes, Insulin Resistance and Immunity: Evolution of Interleukin 7, Fat Mass and Metabolic Profile Before and After Transplantation

Rationale: Due to their ability to store fatty acids and to secrete numerous pro-inflammatory cytokines, adipocytes appear to be key cells 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, whether from its excess (obesity), or its complete (lipoatrophies) or partial absence (lipodystrophies); these 3 different disorders are paradoxically able to induce metabolic insulin resistance syndrome.

Among the involved cytokines, interleukin-7 (IL-7), mostly known for its immune functions, also participates in the quantitative and qualitative balance of fat mass. Thus, IL-7 over-expression in animal models 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 in reactivation of autoimmunity in patients with autoimmune type 1 after islet transplantation.

Otherwise, mammalian target of rapamycin (mTOR) inhibitors have immunosuppressive, metabolic and anti-tumoral properties through different signaling pathways. Rapamycin (or sirolimus) (Rapamune®), an mTOR inhibitor used in islet transplantation, has much greater ability to inhibit adipocyte differentiation and to modulate ß cell function according to the energetic status. In contrast to most organ transplantation, diabetes cell therapy is associated with body weight loss, which is possibly related to the antiadipogenic effects of mTOR inhibitors; the specific role that this plays on the prognostic factors of islet transplantation remains to be determined. Conversely, organ transplantation is usually associated with weight gain, which is involved in the genesis of post-transplantation diabetes, AKA new-onset diabetes after transplantation (NODAT), and long-term vascular complications of transplantation. Adipose tissue redistribution has not yet been studied in patients after transplantation.

The aim of this study is thus to determine blood IL-7 and other cytokine levels; metabolic parameters; and fat mass distribution before and after a immunosuppressive regimen in patients receiving different kinds of transplantation (liver, kidney or islets) with normal weight and no type 2 diabetes before transplantation. In these patients, blood samples will be taken before and after transplantation, as will adipose tissue during the transplantation surgery, in order to constitute a plasma, serum, gene and tissue bank for determining the mechanisms linking fat mass, insulin resistance and immunity, both ex vivo and in vitro.