南方医科大学学报

南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (01): 109-.

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胆汁酸核受体激动剂对脂联素及其受体的影响

辛小敏，钟慕晓，张珊珊，彭 瑶，朱 薇，张亚历   

  • 出版日期:2014-01-20 发布日期:2014-01-20

Effects of farnesoid X receptor agonist on adiponectin and its receptors

  • Online:2014-01-20 Published:2014-01-20

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摘要： 目的观察胆汁酸核受体激动剂GW4064对3T3-L1前脂肪细胞分化过程中脂联素及其受体和对HepG2细胞脂联素受体
的影响。方法用GW4064干预3T3-L1前脂肪细胞的整个分化过程，荧光Real-time PCR法检测分化第0、2、4、6、8天胆汁酸核
受体（FXR）、过氧化物酶体增殖物激活受体γ2（PPARγ2）、脂联素、脂联素受体（AdipoR1、AdipoR2）mRNA相对表达量及ELISA
法检测脂联素蛋白水平，同时，GW4064 干预饥饿后的HepG2 细胞0、12、24、48 h 后，荧光Real-time PCR法检测AdipoR1 和
AdipoR2 mRNA相对表达量。结果GW4064 干预后，3T3-L1 前脂肪细胞中FXR、PPARγ2、脂联素、AdipoR2 及HepG2 细胞
AdipoR2 mRNA相对表达量较空白组明显上升，脂联素蛋白水平与其mRNA表达情况一致，差异均有统计学意义（P<0.05），而
3T3-L1前脂肪细胞、HepG2细胞的AdipoR1表达无明显改变。结论GW4064可上调脂肪细胞FXR、PPARγ2、脂联素、AdipoR2
及HepG2细胞AdipoR2的表达，而脂联素和AdipoR2是治疗非酒精性脂肪性肝病的两个重要因素，因此FXR激动剂可能通过
诱导其表达达到治疗非酒精性脂肪性肝病的目的；另外，PPARγ是脂肪细胞分化成熟的重要调控因子，推测胆汁酸核受体对脂
肪细胞的调控可能是通过上调PPARγ实现的。

Abstract: Objective 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. Methods 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. Results 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. Conculsion
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.