title: Adipogenic effect of calcium sensing receptor activation.
abstract: We established that human adipose cells and the human adipose cell line LS14 express the calcium-sensing receptor (CaSR) and that its activation induces inflammatory cytokine production. Also, its expression is enhanced upon exposure to obesity-associated proinflammatory cytokines. We have thus proposed that CaSR activation may be associated with adipose dysfunction. Here, we evaluated a possible effect on adipogenesis. We induced adipose differentiation of primary and LS14 human preadipocytes with or without the simultaneous activation of CaSR, by the exposure to the calcimimetic cinacalcet. Activation of the receptor for 24 h decreased by 40 % the early differentiation marker CCAAT/enhancer-binding protein β. However, upon longer-term (10 day) exposure to the adipogenic cocktail, cinacalcet exerted the opposite effect, causing a dose-response increase in the expression of the mature adipose markers adipocyte protein 2, adiponectin, peroxisome proliferator-activated receptor γ, fatty acid synthase, and glycerol-3-phosphate dehydrogenase. To assess whether there was a time-sensitive effect of CaSR activation on adipogenesis, we evaluated the 10 day effect of cinacalcet exposure for the first 6, 24, 48 h, 6, and 10 days. Our observations suggest that regardless of the period of exposure, 10 day adipogenesis is elevated by cinacalcet. CaSR activation may interfere with the initial stages of adipocyte differentiation; however, these events do not seem to preclude adipogenesis from continuing. Even though adipogenesis (particularly in subcutaneous depots) is associated with insulin sensitivity and adequate adipose function, the implications of our findings in visceral adipocytes, especially in the context of inflamed AT and overnutrition, remain to be established.
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, 138-11, Casilla, Santiago, Chile.
authors.forename: Pia
authors.initials: P
authors.lastname: Villarroel
authors.forename: Marcela
authors.initials: M
authors.lastname: Reyes
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fuentes
authors.forename: María Pia
authors.initials: MP
authors.lastname: Segovia
authors.forename: Nicolás
authors.initials: N
authors.lastname: Tobar
authors.forename: Elisa
authors.initials: E
authors.lastname: Villalobos
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez
authors.forename: Eric
authors.initials: E
authors.lastname: Hugo
authors.forename: Nira
authors.initials: N
authors.lastname: Ben-Jonathan
authors.forename: Mariana
authors.initials: M
authors.lastname: Cifuentes
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D052242:Adiponectin / Q000096:biosynthesis / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D045744:Cell Line, Tumor; D000069449:Cinacalcet; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D047495:PPAR gamma / Q000096:biosynthesis / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D022782:CCAAT-Enhancer-Binding Protein-beta; D016207:Cytokines; D009281:Naphthalenes; D047495:PPAR gamma; D044169:Receptors, Calcium-Sensing; D005993:Glycerolphosphate Dehydrogenase; D064429:Fatty Acid Synthases; D000069449:Cinacalcet