The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARγ pathway.
Adipocyte differentiation and adipogenesis are closely related to obesity and obesity-induced metabolic disorders. The calcium-sensing receptor (CaSR) has been reported to play an antilipolytic role in human adipocyte and regulate cell differentiation in many tissues. However, the effects of CaSR on adipocyte differentiation and adipogenesis have not been clarified. In the study, we observed that activation of CaSR significantly promoted adipocyte differentiation and adipogenesis in human SW872 adipocytes. Gene expression analysis revealed that the CaSR activation increased the transcription factor proliferator-activated receptor γ (PPARγ) and its downstream genes including CCAAT element binding protein α (C/EBPα), adipose fatty acid-binding protein (aP2), and lipoprotein lipase. The activity of glycerol-3-phosphate dehydrogenase was also increased after the stimulation of CaSR. In addition, levels of cyclic AMP and calcium which have been shown to regulate PPARγ gene expression were significantly affected by the activation of CaSR. These effects could be suppressed by CaSR small interfering RNA (CaSR-siRNA). In conclusion, our findings suggest that activation of CaSR promotes differentiation and adipogenesis in adipocytes, which might be achieved by upregulating PPARγ and its downstream gene expressions. Therefore, CaSR in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis.
Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Nangang District, Harbin, China.
Yong-Han
YH
He
Ying
Y
He
Xi-Lu
XL
Liao
Yu-Cun
YC
Niu
Guan
G
Wang
Chen
C
Zhao
Liang
L
Wang
Ming-Jie
MJ
Tian
Ying
Y
Li
Chang-Hao
CH
Sun
D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; C524662:FABP4 protein, rat; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D044169:Receptors, Calcium-Sensing; D014280:Triglycerides; D005682:Gadolinium; D000242:Cyclic AMP; D008071:Lipoprotein Lipase; C038958:gadolinium chloride