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

Abstract

The high fat diet leads to the development of resistance to leptin and insulin due the installation of an inflammatory process in the hypothalamus, placing this phenomenon with the key in development of obesity. Furthermore, the high fat diet leads to activation of apoptotic signaling pathways that culminate in death of hypothalamic neurons, especially those responsible for the anorexigenic stimulus. Thus, the 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 it´s over expression together with 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 IL-6's ability to induce neurogenesis in the hypothalamus. To this, we are going to use neuronal culture cells and high fat diet Swiss mice treated with IL-6 and then assessed for neurogenesis markers. It will also be evaluated in these animals, hypothalamic cell proliferation, measured food intake, energy expenditure, body weight, leptin and insulin sensitivity 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 open new perspectives for the treatment of this disease.