Cachexia is characterized as a syndrome that affects multiple compartments and systems of the tumor-bearing organism, breaking the natural state of balance between the systems, leading to metabolic "chaos." It is highly prevalent in cancer patients, especially in patients with gastrointestinal cancer (> 60%) and in more than 25% of patients; it is the leading cause of death. Recently, several independent studies have demonstrated that white adipose tissue (WAT), in addition to being described as an organ with important endocrine function, may act as a secretory or target organ of inflammatory molecules during the development of cachexia syndrome. In this way, it seems helpful to investigate the effects of cachexia per se. The current views of the syndrome either as an inflammatory process or as a physiological imbalance so profound as to be proposed as a causative agent and not a consequence of the appearance of tumors demonstrate the insufficiency of the information obtained until the present moment.Acute fat mass reduction is one of the leading clinical "markers" of cancer cachexia. This process seems to be the result of several metabolic and inflammatory changes, due to factors produced by the host itself and by the tumor itself. Thus, having the inflammatory model as a hypothesis to be tested, our group recently demonstrated the relevance of subcutaneous adipose tissue as a vital source of inflammatory mediators, especially IL-6 and adiponectin. These adipokines also presented a cachectic biomarker function (clinical evolution), since these adipokines correlated with the magnitude of reduction of body weight. Also, our recent studies have shown that, in cancer-associated cachexia, morpho-functional changes in WAT are characterized by phenotypic changes in white adipocytes to a profile closer to brown adipocytes. This process, described as browning of WAT, seems to be related to the dysfunction in the energetic metabolism of this tissue.On the other hand, the vast majority of studies are rOn the other hand, most studies are restricted to evaluating morphological changes, neglecting tissue inflammation and, mainly, events that result in alterations in energy metabolism, tissue catabolism and later in systemic inflammation. Because of the role that Toll 4 receptors (TLR4) play in controlling lipolysis, inflammation and consequent remodeling of adipose tissue, we postulate that the activation of these receptors plays an essential role in the reduction of fat mass in cachexia. In this regard, initial data suggest that TLR4 antagonist treatment attenuates TAB remodeling and increases survival of cachexia-carrying mice. Also, despite the critical role of innate immunity receptors as a crossroad between inflammatory and metabolic events, as far as we know, few or no studies have evaluated such relationships and their role in changes in body energy metabolism during cachexia. Thus, we propose to study the effect of cachexia on adipose tissue remodeling, especially the repercussions on body energy metabolism and the possible role of TLR4 as a crossroad between inflammation and energetic metabolism in beige adipocytes.
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