Abstract
Due to the remarkable capacity of brown adipose tissue (BAT) to combust glucose and fatty-acids and the presence of BAT in adult humans, this tissue has been considered as an attractive target for the treatment or prevention of type-2 diabetes (T2DM)/obesity. Nonetheless, BAT activation results in improved insulin sensitivity and glucose utilization in other tissues, such as liver or muscle. These distal effects are a consequence of BAT capacity to act as a secretory organ, releasing factors that mediate its peripheral effects. While cold is known as an effective way to activate BAT and to provoke several beneficial metabolic effects, identification of the molecular mimetics of cold exposure will provide new avenues for the prevention and treatment of metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). The use of metabolomics technologies combined with genetic models has helped to identify several lipid mediators that serve as metabolic messengers to communicate the energy status and modulate substrate utilization among tissues. NAFLD takes place as a consequence of a high-fat and mainly high-carbohydrate diet and plays a pivotal role connecting obesity with type-2 diabetes and cardiovascular diseases. BAT and liver communicates through the release of factors that can modulate each other functions. Based on our preliminary data, we hypothesized that brown adipose tissue is capable of biosynthesizing and secreting lipid metabolites that regulate hepatic function and gene expression profile. We therefore propose that the cold-induced omega-3 metabolites such as 12-HEPE, 14-HDHA and Maresin-2 are produced in BAT under cold through increased 12-lipoxygenase activity and then released into the circulation, thus suppressing liver lipogenesis, hepatic glucose production and triglycerides synthesis by stimulating G-coupled protein receptors in the liver. In the present project we present a comprehensive and innovative approach in order to elucidate the BAT-liver cross talk and identify/characterize novel omega-3 lipid metabolites capable of ameliorating NAFLD and T2DM. (AU)
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