The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARγ pathway

Abstract

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.

Association Between Cytosolic Glycerol 3-Phosphate Dehydrogenase Gene Expression in Human Subcutaneous Adipose Tissue and BMI

“…Coordinated up-regulation of PPARγ and cGPDH genes expression during adipocyte differentiation and adipogenesis was also recently reported [30]. Current data indicates that resveratrol [31] or kefir [32] coordinately decrease lipid accumulation, cGPDH activity, and PPARγ gene expression in 3T3-L1 adipocytes.…”

Expression of multiple Transient Receptor Potential channel genes in murine 3T3-L1 cell lines and adipose tissue

“…A study from Hu and colleagues demonstrated the molecular identities of calcium signaling pathways in human preadipocytes [2]. Further, in human adipocytes, increases in cytosolic calcium exhibited a biphasic effect (increase in cytosolic calcium inhibited the early stages but enhanced the late stage of differentiation) in the regulation of adipocyte differentiation [1,8]. Calcium activated downstream signaling in the cell includes both pro-and antiadipogenic factors.…”

The activity of transient receptor potential channel C‐6 modulates the differentiation of fat cells

“…Other calcium‐binding factors like the G‐protein–coupled extracellular calcium‐sensing receptor (CaSR) (44) and calcineurin (45) have been associated with adipocyte differentiation. Activated CaSRs in response to changes in extracellular calcium concentration promotes adipocyte differentiation by increasing PPARγ and its downstream expressions of C/EBPα, aP2, and lipoprotein lipase.…”