title: Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue.
abstract: The proinflammatory status of adipose tissue has been linked to the metabolic and cardiovascular consequences of obesity. Human adipose cells express the calcium sensing receptor (CaSR), and its expression is elevated in inflammatory states, such as that associated with obesity. Given the CaSR's association with inflammation in other tissues, we evaluated its role elevating the adipose expression of inflammatory factors. The CaSR activation by the calcimimatic cinacalcet (5μM) in adipose tissue and in vitro cultured LS14 adipose cells elicited an elevation in the expression of the proinflammatory cytokines IL6, IL1β, TNFα, and the chemoattractant CCL2. This was in part reverted by SN50, an inhibitor of the inflammatory mediator nuclear factor kappa B (NFκB). Our observations suggest that CaSR activation elevates cytokine and chemokine production, partially mediated by NFκB. These findings support the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction, with an interesting potential for pharmacological manipulation.
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile. mcifuentes@inta.uchile.cl
authors.forename: Mariana
authors.initials: M
authors.lastname: Cifuentes
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fuentes
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tobar
authors.forename: Ingrid
authors.initials: I
authors.lastname: Acevedo
authors.forename: Elisa
authors.initials: E
authors.lastname: Villalobos
authors.forename: Eric
authors.initials: E
authors.lastname: Hugo
authors.forename: Nira
authors.initials: N
authors.lastname: Ben-Jonathan
authors.forename: Marcela
authors.initials: M
authors.lastname: Reyes
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D000069449:Cinacalcet; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: C095550:CASR protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D009281:Naphthalenes; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D000069449:Cinacalcet