title: Obesity-associated proinflammatory cytokines increase calcium sensing receptor (CaSR) protein expression in primary human adipocytes and LS14 human adipose cell line.
abstract: Obesity-associated health complications are thought to be in part due to the low-grade proinflammatory state that characterizes this disease. The calcium sensing receptor (CaSR), which is expressed in human adipose cells, plays an important role in diseases involving inflammation. To assess the relevance of this protein in adipose pathophysiology, we evaluated its expression in adipocytes under obesity-related proinflammatory conditions. As in primary adipose cells, we established that LS14, a recently described human adipose cell line, expresses the CaSR. Differentiated LS14 and primary adipose cells were exposed overnight to cytokines typically involved in obesity-related inflammation (interleukin (IL)1beta, IL6 and tumor necrosis factor (TNF)alpha). The cytokines increased CaSR abundance in differentiated adipocytes. We incubated LS14 cells with medium previously conditioned (CM) by adipose tissue from subjects with a wide range of body mass index (BMI). Cells exposed to CM from subjects of higher BMI underwent a greater increase in CaSR protein, likely resulting from the greater proinflammatory cytokines secreted from obese tissue. Our observations that proinflammatory factors increase CaSR levels in adipocytes, and the reported ability of CaSR to elevate cytokine levels, open new aspects in the study of obesity inflammatory state pathophysiology, providing a potential novel therapeutic prevention and treatment target.
authors.affiliation: Institute of Nutrition and Food Technology, Universidad de Chile, Chile. mcifuentes@inta.cl
authors.forename: Mariana
authors.initials: M
authors.lastname: Cifuentes
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fuentes
authors.forename: Pamela
authors.initials: P
authors.lastname: Mattar
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tobar
authors.forename: Eric
authors.initials: E
authors.lastname: Hugo
authors.forename: Nira
authors.initials: N
authors.lastname: Ben-Jonathan
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rojas
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C095550:CASR protein, human; D017077:Culture Media, Conditioned; D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D044169:Receptors, Calcium-Sensing; D014409:Tumor Necrosis Factor-alpha