Abstract
Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue (WAT) is an active endocrine organ, with a crucial influence on whole-body homeostasis. WAT dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease, and some cancers. Among the regulators of WAT physiology, the calcium-sensing receptor (CaSR) has arisen as a potential mediator of WAT dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that CaSR activation in the visceral (i.e., unhealthy) WAT is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to CaSR activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in WAT plays a key role in the development of WAT dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that CaSR may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.
Highlights
Obesity has turned into a pandemic disease, with a worldwide prevalence that has more than doubled in the last three decades, even after multiple attempts to stop its expansion1
Our group showed the presence of the Calcium-sensing receptor (CaSR) in human preadipocytes and adipocytes (Cifuentes et al, 2005), and studies in the last decade suggest that its activation is involved in white adipose tissue (WAT) dysfunction (Villarroel et al, 2014)
Obesity is a complex and multifactorial disease, and even though it is known that energy imbalance is at the core of the problem, it has been extremely difficult to decrease or control the worldwide obesity epidemic
Summary
Obesity has turned into a pandemic disease, with a worldwide prevalence that has more than doubled in the last three decades, even after multiple attempts to stop its expansion. It is known that white adipose tissue (WAT) dysfunction is key in the pathophysiology of obesity-related diseases, and the study of novel regulators of this process is crucial to uncover new therapeutic targets In this context, our group showed the presence of the Calcium-sensing receptor (CaSR) in human preadipocytes and adipocytes (Cifuentes et al, 2005), and studies in the last decade suggest that its activation is involved in WAT dysfunction (Villarroel et al, 2014). CaSR activation with the calcimimetic cinacalcet increases the expression of IL1β, IL6, TNFα, and CCL2 in LS14 preadipocytes and adipocytes as well as human visceral WAT explants These changes were dependent on NFκB signaling in LS14 cells (Cifuentes et al, 2012), highlighting the intimate, tripartite relationship between CaSR-NFκB-cytokines during inflammation in adipose cells (Figure 2B)
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