瞬时感受器电位离子通道V亚家族成员4基因敲除对小鼠血脂和脂肪组织的影响

Effect of transient receptor potential vanilloid 4 knockout on mouse blood lipids and adipose tissue

目的探讨瞬时感受器电位离子通道V亚家族成员4(TRPV4)基因敲除对小鼠血脂水平以及脂肪组织的影响。方法观察野生型C57BL/6J小鼠和TRPV4基因敲除(TRPV4^(-/-))小鼠在高脂饮食饲养后体质量、脂肪质量、血脂水平变化以及肩胛间棕色脂肪组织(iBAT)、腹股沟白色脂肪组织(iWAT)及附睾白色脂肪组织(eWAT)的激活情况;利用3T3-L1脂肪细胞观察TRPV4激动剂对脂肪棕色化基因PR结构域蛋白16(PRDM16)表达的影响。结果在高脂饮食喂养16周后,TRPV4^(-/-)小鼠的血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)均较野生型小鼠升高,差异有统计学意义(P<0.05);体质量和脂肪组织质量均较野生型小鼠减轻,但差异无统计学意义(P>0.05),TRPV4^(-/-)小鼠脂肪组织呈棕色化趋势较野生型小鼠明显;加入TRPV4激动剂后,3T3-L1脂肪细胞PRDM16基因和蛋白表达水平上调(P<0.05)。结论TRPV4基因敲除能够升高血脂水平并促进脂肪组织棕色化。

Objective To investigate the effect of transient receptor potential vanilloid 4(TRPV4)knockout(TRPV4^(-/-))on mouse blood lipid level and adipose tissue.Methods After feeding on a high-fat diet,the changes of body mass,adipose tissue mass,blood lipid level and the activation of interscapular brown adipose tissue(iBAT),inguinal white adipose tissue(iWAT)and epididymis white adipose tissue(eWAT)were examined in C57BL/6J wild-type mice and TRPV4^(-/-)mice.In 3T3-L1 adipocytes,the effect of TRPV4 agonist on the expression of a fat browning gene--PR domain protein 16(PRDM16)was observed.Results After 16 weeks of feeding on a high-fat diet,serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C)were higher in TRPV4^(-/-)mice than those in wild-type mice(P<0.05).The masses of body and adipose tissue were slightly less in TRPV4^(-/-)mice than those in wild-type mice(P>0.05).The adipose tissue of TRPV4^(-/-)mice exhibited a more pronounced browning trend than wild-type mice did.TRPV4 agonist upregulated the mRNA and protein expression levels of PRDM16 in 3T3-L1 adipocytes(P<0.05).Conclusion Knockout of TRPV4 gene can increase blood lipid levels and promote browning of adipose tissue.