胆汁酸核受体激动剂对瘦素及OB-Rb的影响

Effects of FXR agonist on leptin and OB-Rb

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瘦素及长型瘦素受体(OB-Rb)和对HepG2细胞OB-Rb的影响。方法:用GW4064干预3T3-L1前脂肪细胞的分化过程,采用荧光real-time PCR法检测分化过程中第0、2、4、6、8天瘦素及OB-Rb mRNA相对表达量及ELISA法检测瘦素分泌情况,同时,用GW4064干预饥饿后的HepG2细胞0、12、24、48 h后,荧光real-time PCR法检测OBRb mRNA相对表达量。结果 :GW4064干预后,3T3-L1前脂肪细胞中瘦素mRNA相对表达量较对照组明显上升,瘦素蛋白分泌情况与其mRNA表达相似,差异均有统计学意义(均P<0.05),而OB-Rb mRNA表达无明显改变(P>0.05);同时,HepG2细胞的OB-Rb mRNA在干预后表达明显增加,差异有统计学意义(P<0.001)。结论 :GW4064可上调脂肪细胞瘦素和HepG2细胞OB-Rb的表达,目前瘦素在非酒精性脂肪性肝病中的作用及机制尚不明确,而OB-Rb的低表达则与非酒精性脂肪性肝病中的瘦素抵抗相关,因此,我们推测胆汁酸核受体激动剂可通过提高肝脏OB-Rb的表达改善瘦素抵抗,从而达到治疗非酒精性脂肪性肝病的目的。

Objective To investigate the effects of GW4064, one FXR agonist, on the leptin and OB-Rb during the differentiation of 3T3-L1 preadipocytes and on the OB-Rb in the HepG2 cells. Methods The mRNA relative expression of leptin, OB-Rb and the protein of leptin on the day of 0, 2, 4, 6, 8 during the differentiation of 3T3-L1 preadipocytes after interfered with GW4064 were detected by fluorescent real-time PCR and ELISA, respectively. Meanwhile, the mRNA relative expression of OB-Rb of HepG2 cells after treated with GW4064 0 h, 12 h, 24 h, 48 h were also examined. Results The mRNA relative expression of leptin in the 3T3-L1 preadipocytes and OB-Rb in the HepG2 cells after treated with GW4064 were significantly increased compared with the controlgroup. Also, the protein level of leptin was similar with the mRNA expression. The all differences were statistically significance （P 〈 0.05）. However, there was no significant difference on OB-Rb in 3T3-L1 preadipocytes cells （P 〉 0.05）. Conclusions GW4064 is able to upregulate the expression of leptin in the 3T3-L1 preadipocytes and OB- Rb in the HepG2 cells. Now the role of leptin in the NAFLD is still unkown, however, the low expression of OB-Rb is related with the leptin resistance in the pathogenesis of NAFLD. So we hypothesize that FXR agonist may treat NAFLD through upreglating the expression of OB-Rb and improving leptin resistance.