Cancer-induced cachexia (CC), characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling, and muscle wasting, is a malignant metabolic syndrome with an undefined etiology. There is a consensus that multiple factors contribute to cancer-induced AT remodeling, and longitudinal studies show that patients lose AT before they start losing muscle mass. In CC, AT remodeling occurs predominantly through adipocyte atrophy, impairment of fatty acid turnover, inflammation, rearrangement of extracellular matrix (ECM), and browning of AT. More recently, some studies have shown that AT is affected early in the course of cachexia. Additionally, studies using experimental models have consistently indicated that the alterations in adipocyte metabolism begin quite early, followed by the downregulation of adipogenic and thermogenic genes. These sets of changes, in addition to metabolites derived from this process, maybe the initial (sterile) trigger of the sequence of events that result in the remodeling and dysfunction of AT in cachexia. Therefore, the present chapter aims to describe state of the art related to the subject of interest by analyzing the primary studies that have addressed the possible interface between inflammation and morphofunctional alterations of AT, in addition to the possible repercussions of this process during the development of CC.
Part of the book: Muscle Cells
Adipose tissue not only possesses an important role in the storage of excess nutrients but also acts as a critical immune and endocrine organ. Researchers and clinicians now consider adipose tissue to be an active endocrine organ that secretes various humoral factors called “adipokines,” which imparts important systemic metabolic effects, from food intake to glucose tolerance. Along with its production of specialized adipokines, adipose tissue also secretes proinflammatory cytokines that likely contributes to the low-level systemic inflammation that has become a hallmark of various metabolic syndrome-associated chronic pathologies, such as obesity and cancer cachexia. These systemic effects may be mediated by communication networks arising from the multitude of resident adipose cells, including adipocytes, endothelial cells, neuronal cells, stem cells and other precursors, and a wide variety of immune cell populations that recent studies have demonstrated play a crucial role in the development of adipose inflammation and systemic metabolic abnormalities. In this chapter, we detail various molecular pathways linking excess adipose lipid storage to chronic inflammation and review the current knowledge as to what triggers obesity- and cachexia-associated inflammation in adipose tissue. Finally, we describe how the cross talk between adipose tissue inflammation and the non-adipocyte resident cells present in tissue is involved in this metabolic disruption.
Part of the book: Adipose Tissue