Xin Xiaomin, Zhong Muxiao, Zhang Shanshan, Peng Yao, Zhu Wei, Zhang Yali
Institute of Digestive Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2014 Jan;34(1):109-12.
To investigate the effects of GW4064, a farnesoid X receptor (FXR) agonist, on adiponectin and its receptors during the differentiation of 3T3-L1 preadipocytes and on adiponectin receptors in HepG2 cells.
The mRNA expressions of FXR, PPARγ2, adiponectin, AdipoR1, and AdipoR2 and the protein levels of adiponectin on days 0, 2, 4, 6, and 8 during the differentiation of 3T3-L1 preadipocytes treated with GW4064 were detected by fluorescent real-time PCR and ELISA, respectively. The mRNA expressions of AdipoR1 and AdipoR2 in HepG2 cells were also examined at 0, 12, 24, and 48 h after GW4064 treatment.
The mRNA expressions of FXR, PPARγ2, adiponectin, and AdipoR2 in 3T3-L1 preadipocytes and AdipoR2 in HepG2 cells treated with GW4064 was significantly increased compared with the control group (all P<0.05). The protein level of adiponectin was also significantly increased after GW4064 treatment. The expression of AdipoR1 in either 3T3-L1 preadipocytes or HepG2 cells showed no significant changes after GW4064 treatment.
GW4064 can up-regulate the expressions of FXR, PPARγ2, adiponectin, AdipoR2 in 3T3-L1 preadipocytes and AdipoR2 in HepG2 cells. As adiponectin and its receptors are two important factors in the treatment of non-alcoholic fatty liver disease, FXR agonist may potentially produce therapeutic effect on non-alcoholic fatty liver disease and can regulate adipocytes via up-regulating PPARγ during adipocyte differentiation.
研究法尼酯X受体（FXR）激动剂GW4064对3T3-L1前脂肪细胞分化过程中脂联素及其受体的影响，以及对HepG2细胞中脂联素受体的影响。
分别采用荧光实时定量PCR和ELISA法检测GW4064处理的3T3-L1前脂肪细胞在分化第0、2、4、6和8天FXR、PPARγ2、脂联素、AdipoR1和AdipoR2的mRNA表达以及脂联素的蛋白水平。同时检测GW4064处理HepG2细胞0、12、24和48小时后AdipoR1和AdipoR2的mRNA表达。
与对照组相比，GW4064处理的3T3-L1前脂肪细胞中FXR、PPARγ2、脂联素和AdipoR2的mRNA表达以及HepG2细胞中AdipoR2的mRNA表达均显著增加（均P<0.05）。GW4064处理后脂联素的蛋白水平也显著增加。GW4064处理后，3T3-L1前脂肪细胞或HepG2细胞中AdipoR1的表达均无显著变化。
GW4064可上调3T3-L1前脂肪细胞中FXR、PPARγ2、脂联素、AdipoR2的表达以及HepG2细胞中AdipoR2的表达。由于脂联素及其受体是非酒精性脂肪性肝病治疗中的两个重要因素，FXR激动剂可能对非酒精性脂肪性肝病产生治疗作用，并可在脂肪细胞分化过程中通过上调PPARγ来调节脂肪细胞。
