title: Preadipocyte proliferation is elevated by calcium sensing receptor activation.
abstract: Obesity is a major worldwide problem, despite considerable efforts against it. While excess body fat defines obesity, adipose tissue quality and functionality are key to whether cardiovascular and metabolic comorbidities develop. Adipose tissue cellular composition can vary considerably, and excess adipocyte progenitors (preadipocytes) is associated with obesity. We have proposed that calcium sensing receptor (CaSR) activation in adipose tissue leads to dysfunction. This study evaluated whether CaSR activation elevates preadipocyte proliferation. Human LS14 preadipocytes were exposed to CaSR activators cinacalcet (2 µM), GdCl3 (5 µM) and spermine (1 µM), and cell viability was evaluated after 72h. CaSR activators elevated proliferation by 19-24%, and CaSR silencing (siRNA) abolished the effect. Cinacalcet elevated phospho-ERK1/2 content, and upstream inhibition of ERK1/2 phosphorylation reverted cinacalcet-induced proliferation. Cinacalcet also elevated expression of the proinflammatory factors IL1β, IL6 and CCL2. The results suggest that CaSR induces preadipocyte proliferation, partly through ERK1/2 activation. Considering reported proinflammatory and adipogenic CaSR effects, excess preadipocyte proliferation further supports the dysfunctional effect of CaSR in obesity.
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Gladys
authors.initials: G
authors.lastname: Rocha
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Elisa
authors.initials: E
authors.lastname: Villalobos
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fuentes
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Pia
authors.initials: P
authors.lastname: Villarroel
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Marcela
authors.initials: M
authors.lastname: Reyes
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Ximena
authors.initials: X
authors.lastname: Díaz
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mattar
authors.affiliation: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile. Electronic address: mcifuentes@inta.uchile.cl.
authors.forename: Mariana
authors.initials: M
authors.lastname: Cifuentes
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020935:MAP Kinase Signaling System; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*
chemical_list: C095550:CASR protein, human; D016207:Cytokines; D044169:Receptors, Calcium-Sensing
keywords: Adipose; Calcium sensing receptor; Dysfunction; Obesity; Preadipocyte; Proliferation