CYP1B1基因敲除对高脂膳食诱导小鼠肥胖的抑制作用

Inhibition Effect of CYP1B1 Deficiency on Obesity Mice Caused by High Fat Diet

目的从整体水平探讨基因CYP1B1在机体脂肪代谢中的作用。方法选择3周龄SPF级CYP1B1基因敲除(KO)和野生型(WT)雄性小鼠各16只,给予低(LFD)、高脂肪(HFD)饲料,每组8只。连续喂养11周。测定血清中甘油三酯(TG)的含量和肝脏组织中过氧化物酶体增殖物激活受体(PPAR-γ)、脂肪酸转移酶(CD36)、肉毒碱棕榈酰基转移酶(CPT-1α)、脂肪酸合成酶(FAS)、硬脂酰辅酶A去饱和酶1(SCD-1)、解耦联蛋白2(UCP2)、甘油-3-磷酸转酰酶(GPAT)、二酰基甘油酰基转移酶1(DGAT-1)、亲环蛋白Cyclophilin mRNA以及磷酸腺苷激活蛋白激酶(AMPK)蛋白的表达水平。结果经过11周喂养后,与WT-LFD组相比,WT-HFD组小鼠体重、附睾脂肪组织重量及其脏器系数,脂肪细胞体积,肝脏系数及甘油三酯含量均显著升高(P<0.05);肝组织中FAS、CPT-1α、UCP2、PPAR-γ、CD36的表达增强(P<0.05),而SCD-1、DGAT-1、GPAT的表达减弱(P<0.05)。与WT-HFD组比较,KO-HFD组小鼠的体重、附睾脂肪组织重量及其脏器系数、体脂分布以及脂肪细胞体积均显著降低(P<0.05),其血甘油三酯含量及肝脏组织脂肪含量亦明显降低(P<0.05)。肝脏组织基因表达分析显示,CYP1B1敲除可抑制FAS、SCD-1、DGAT-1、GPAT以及PPAR-γ和CD36的表达(P<0.05),促进CPT-1α、UCP2的表达(P<0.05);同时,促进AMPK蛋白的表达。结论 CYP1B1基因敲除对营养性肥胖的保护作用可能与AMPK调控肝脏组织脂肪代谢相关基因表达有关。

Objective To investigate the role of CYP1B1 in fat metabolism.Methods Sixteen male CYP1B1 knock-out（KO） mice and sixteen wild type（WT） mice（C57） were both randomly divided into low-fat-diet（LFD） and high-fat-diet（HFD） groups.All mice were fed right after wean for 11 consecutive weeks.The mice were scarified at the age of 14 weeks,the blood,liver and epididymis fat pad were collected and the related indexes were determined.Results After 11 weeks of feeding,the body weight,epididymis fat pad weight and relative weight,lipocyte size,liver relative weight and TG content were significantly higher in the WT-HFD group compared with the WT-LFD group.The expression of gene FAS,CPT-1α,UCP2,PPAR-γ and CD36 in the liver were also higher in the WT-HFD group,but the expression of gene SCD-1,DGAT-1,GPAT were lower.Compared with the WT-HFD group,the body weight,epididymis fat pad weight and relative weight,the distribution of body fat,lipocyte size TG content and fat content in liver were significantly lower in the KO-HFD group.The analysis of gene expression in the liver showed that,the CYP1B1 deletion significantly suppressed the expression of gene FAS,SCD-1,DGAT-1,GPAT,PPAR-γ and CD36,enhanced the expression of CPT-1α,UCP2 and protein AMPK.Conclusion The antagonism of CYP1B1 knock-out to high fat diet induced obesity in mice may be related with a sets of genes expression which involved in fat metabolism in liver through AMPK activation pathway.