title: Calcium sensing receptor effects in adipocytes and liver cells: Implications for an adipose-hepatic crosstalk.
abstract: The calcium sensing receptor (CaSR) is expressed in human adipose cells, and its activation may associate with adipose tissue (AT) dysfunction. We evaluated whether CaSR stimulation influences adipocyte triglyceride (TG) and fatty acid binding protein 4 (aP2) content, and hepatocyte TGs and proinflammatory cytokine expression. The effect of the calcimimetic cinacalcet on TGs (fluorimetry), lipogenic genes (qPCR) and aP2 (immunoblot) was evaluated in LS14 adipocytes or AT. In the human HepG2 hepatic cell line, we assessed CaSR expression and cinacalcet effect on TGs and lipogenic and proinflammatory genes. CaSR activation decreased adipocyte TG content by 20% and the expression of GPD and LPL by 34% and 20%, respectively. Cinacalcet increased aP2 protein expression by 60%. CaSR expression was shown in HepG2 cells and human liver samples. Cinacalcet-treated HepG2 cells in the presence of oleic acid exhibited a19% increased TG content. No changes were observed in the expression of lipogenic genes in HepG2 cells, however there was a 50%-300% elevation in the expression of proinflammatory cytokines. CaSR activation in adipocytes may associate with decreased TG storage ability and increased aP2. Hepatic CaSR stimulation may elevate steatosis and proinflammatory factors. We propose that CaSR may contribute to obesity-associated hepatic metabolic consequences.
authors: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors: Pia
authors: P
authors: Villarroel
authors: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors: Pamela
authors: P
authors: Mattar
authors: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors: Amanda
authors: A
authors: D'Espessailles
authors: Gastroenterology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Marco
authors: M
authors: Arrese
authors: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors: Andrea
authors: A
authors: Arreguin
authors: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors: Cecilia
authors: C
authors: Fuentes
authors: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile.
authors: Marcela
authors: M
authors: Reyes
authors: Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile. Electronic address: mcifuentes@inta.uchile.cl.
authors: Mariana
authors: M
authors: Cifuentes
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D000069449:Cinacalcet / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D016207:Cytokines; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D044169:Receptors, Calcium-Sensing; D014280:Triglycerides; D012313:RNA; D000069449:Cinacalcet
keywords: Adipocyte; Calcium sensing receptor; Hepatocyte; Lipogenesis; aP2