Evaluation of the capacity of IL-6 to induce neurogenesis in the hypothalamus

Abstract

A high fat diet (HFD) leads to development of resistance to leptin and insulin because of the installation of an inflammatory process in the hypothalamus, a key phenomenon link the development of obesity. Furthermore, a HFD leads to an apoptotic signaling pathways that culminate in death of hypothalamic neurons, especially those responsible for the anorexigenic stimulus. As a result, hypothalamic neurogenesis is gaining interest. Studies have shown that in IL-6 Knockout mice there is a decrease in protection of neuronal damage in the hippocampus and over expression of IL-6 and its soluble receptor led to an increased regeneration of neurons. It is also known that IL-6 plays critical role in the survival of neurons during development and adulthood injury. Therefore, we hypothesized that IL-6 can not only reduce inflammation, but also increase the hypothalamic neurogenesis. Thus, the main objective of this study is to evaluate the ability of IL-6 to induce neurogenesis in the hypothalamus. To this, neuronal cells culture and Swiss mice in a HFD will be treating with IL-6 and then assessed for neurogenesis markers. It will be also evaluated in hypothalamus of these animals after the IL-6 treatment, cell proliferation and measured caloric intake, body weight, sensitivity to leptin and insulin and glucose intolerance. We believe that this study will contribute to advances in knowledge about the mechanisms involved in the development of diet-induced obesity and that will open new perspectives for the treatment of this disease. (AU)