Purinergic 2X7 receptor is involved in adipogenesis and lipid degradation

Obesity and dyslipidemia are two metabolic syndrome disorders that have serious effects on the health of patients. Purinergic 2X receptor ligand-gated ion channel 7 (P2X7R) has been reported to play a role in regulating lipid storage and metabolism. However, the role and potential mechanism of P2X7R in adipogenesis and lipid degradation remain unknown. In the present study, a mouse model of obesity was established by feeding mice a high-fat diet, and the 3T3-L1 cell line was used to analyze the function of P2X7R in vitro. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of P2X7R, sterol regulatory element-binding protein 1 (SREBP1) and other associated transcription factors. Bioinformatics analysis was used to predict the potential target gene of P2X7R and a dual luciferase reporter assay was used to confirm this prediction. Oil Red O staining was used to evaluate the adipogenic capacity of preadipocytes. AdipoRed assay, cholesterol assay and a free glycerol reagent were used to measure the expression levels of triglyceride (TGs), total cholesterol (TC) and glycerin, respectively. The results indicated that P2X7R was highly expressed in obese mice and that it was involved in adipogenic differentiation in vitro. SREBP1 enhanced the transcription activities of P2X7R to promote its expression. Inhibition of P2X7R significantly reduced the adipogenic capacity of preadipocytes, decreased the expression levels of adipogenesis-associated transcription factors (peroxisome proliferator-activated receptor γ, CCAAT-enhancer-binding protein α and fatty-acid-binding protein 4), enhanced the expression levels of lipolytic enzymes (adipose triglyceride lipase, phosphorylated hormone-sensitive lipase and monoacylglycerol lipase) and regulated the expression of TG, TC and glycerin in mature 3T3-L1 cells. These effects were reversed by a small interfering RNA targeting Wnt3a. Therefore, the results suggested that P2X7R, the transcription activities of which were regulated by SREBP1, regulated adipogenesis and lipid degradation by targeting SREBP1, indicating its potential effects on obesity-associated metabolism.