title: Calcium Sensing Receptor as a Novel Mediator of Adipose Tissue Dysfunction: Mechanisms and Potential Clinical Implications.
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.
authors.affiliation: Institute of Nutrition and Food Technology, University of ChileSantiago, Chile; Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases and Center for Molecular Studies of the Cell, University of ChileSantiago, Chile.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bravo-Sagua
authors.affiliation: Institute of Nutrition and Food Technology, University of ChileSantiago, Chile; Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases and Center for Molecular Studies of the Cell, University of ChileSantiago, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mattar
authors.affiliation: Institute of Nutrition and Food Technology, University of Chile Santiago, Chile.
authors.forename: Ximena
authors.initials: X
authors.lastname: Díaz
authors.affiliation: Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases and Center for Molecular Studies of the Cell, University of ChileSantiago, Chile; Cardiology Division, Department of Internal Medicine, University of Texas Southwestern Medical CenterDallas, TX, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
authors.affiliation: Institute of Nutrition and Food Technology, University of Chile Santiago, Chile.
authors.forename: Mariana
authors.initials: M
authors.lastname: Cifuentes
keywords: CaSR; adipocyte; adipose tissue dysfunction; inflammation; obesity; preadipocyte