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Investigation of the molecular mechanisms involved in the antiobesity effect of Camellia sinensis

Abstract

The advancement of the obesity epidemic, which now affects approximately one-third of adults around the world, underscores the relevance of the detailed study of adipose tissue. Adipose tissue is no longer considered a mere storage site for excess energy as it was 20 years ago. Instead, years of intense research have brought to the surface the image of a highly active tissue involved in numerous metabolic, hormonal, and immunological processes, whose products and reactions are able to act not only locally, but also influence other organs and systems playing a crucial role in whole body homeostasis. The high prevalence of obesity in the population arouses the scientific interest in the search for therapeutic interventions capable of promoting loss of fat mass and of preventing associated comorbidities. In this sense, many researchers try to find bioactive compounds derived from natural products with pharmacological properties capable of treating and/or preventing obesity, modulating adipose tissue activity. Although considerable progress has been made in understanding the molecular mechanisms underlying obesity, there is still a huge gap in the understanding of the pathophysiology of the disease, indicating the need for further studies. Our research group has for some time been studying the effects of different compounds with nutraceutical properties on metabolic dysfunctions such as DM2 in animal models and cells. We are currently investigating in different cells in vitro and in vivo tissues the effects of the Camellia sinensis plant for the treatment of obesity and its complications. The first researches of our group involving green tea (GT) and obesity corroborated with data from the literature and pointed out a significant role of GT as anti-inflammatory, thermogenic (induction of beige adipocytes and activation of brown adipose tissue), antioxidant, adipose tissue reducer, in addition to improving insulin resistance and glycemic homeostasis. However, the cellular and molecular mechanisms involved in the various beneficial actions of GT need to be clarified, although we have strong evidence of the involvement of the PPAR transcription factor and beige adipocytes in the beneficial actions of GT. Therefore, in general, in the present project, we intend to investigate the molecular mechanisms that involve PPARg and induce a greater energetic expenditure in obese mice treated with GT, using for this purpose, mice with partial deletion of PPARg. In addition, we aim to evaluate the immune population present in epididymal, subcutaneous and brown adipose tissue of wild animals exposed to a HFD and treated with CV. This analysis will be by flow cytometry for immunophenotyping and identification of macrophage subpopulations (M0, M1, M2), eosinophils, lymphocytes (TCD4, TCD8, NKT, Th1, Th2, Tdg, Treg, Th17) and neutrophils. This project is set up as a sequential research work of the first researches initiated with bioactive compounds of plants for the treatment of obesity and that will qualitatively enrich the preliminary data already obtained by the research group. The findings of this study may present important value in translational studies for humans. (AU)