GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells

AIM:To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2cells.METHODS:The mRNA expression of farnesoid X receptor(FXR),peroxisome proliferator-activated receptor-gamma 2(PPAR-γ2),adiponectin,leptin,resistin,adiponectin receptor 1(AdipoR1),adiponectin receptor2(AdipoR2),and the long isoform of leptin receptor(OB-Rb)and protein levels of adiponectin,leptin,andresistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay,respectively,on days 0,2,4,6,and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064.Moreover,mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0,12,24,and 48 h in HepG2 cells treated with GW4064.RESULTS:The mRNA expression of FXR,PPAR-γ2,adiponectin,leptin,resistin,AdipoR1,AdipoR2,and OB-Rb and protein levels of adiponectin,leptin,and resistin increased along with differentiation of 3T3-L1preadipocytes(P<0.05 for all).The mRNA expression of FXR,PPAR-γ2,adiponectin,leptin,and AdipoR2in 3T3-L1 preadipocytes,and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064,when compared with the control group(P<0.05 for all).A similar trend was observed for protein levels of adipokines(including adiponectin,leptin and resistin).However,the expression of resistin,AdipoR1,and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064.CONCLUSION:The FXR agonist through regulating,at least partially,the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.

益气养阴活血方对2型糖尿病大鼠脂肪组织及瘦素、脂联素的影响

目的观察益气养阴活血方对2型糖尿病胰岛素抵抗大鼠脂肪组织及瘦素、脂联素的影响。方法 60只健康雄性SD大鼠适应性喂养1周后,随机择取10只作为正常组,其余大鼠以高脂饮食饲养加小剂量链脲佐菌素(STZ)腹腔注射的方法建立2型糖尿病胰岛素抵抗大鼠模型,将成模大鼠随机分为模型组10只、益气养阴活血方高剂量组10只、益气养阴活血方中剂量组9只、益气养阴活血方低剂量组10只和津力达组9只。各药物组大鼠分别予相应药物灌胃,正常组和模型组给予等量生理盐水灌胃。灌胃4周后,取各组大鼠腹主动脉血,采用酶免法检测血清瘦素、脂联素、胰岛素水平,以生化法检测空腹血糖水平,并计算胰岛素敏感指数(IAI)和胰岛素抵抗指数(HOMA-IR);取各组大鼠肾周脂肪组织,于光镜下观察脂肪组织形态学。结果与模型组比较,益气养阴活血方各剂量组及津力达组大鼠IAI、脂联素水平明显升高(P均<0.05),HOMA-IR、瘦素水平明显降低(P均<0.05),脂肪细胞面积明显减小(P均<0.05),炎细胞浸润和毛细血管扩张充血也明显减少。结论益气养阴活血方可改善2型糖尿病大鼠胰岛素抵抗状态,其作用的发挥可能与其改善脂肪组织的肥大和炎症反应,并正向调节瘦素、脂联素水平有关。