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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 the body fat metabolism from the overall level. Methods 16 male SPF CYP1B1 knockout (KO) and wild type (WT) mice of 3 weeks old were given low and high fat (HFD) diets, 8 in each group. Fed for 11 weeks. Serum levels of triglyceride (TG) and peroxisome proliferator activated receptor (PPAR-γ), fatty acid transferase (CD36) and carnitine palmitoyltransferase (CPT- , Fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD-1), uncoupling protein 2 (UCP2), glycerol- 3 -phosphate transacylase (GPAT), diacylglycerol acyltransferase 1 (DGAT-1), cyclophilin Cyclophilin mRNA and AMPK protein expression. Results Compared with WT-LFD group, body weight, epididymal fat mass, organ coefficient, fat cell volume, hepatic coefficient and triglyceride content in WT-HFD group were significantly increased after 11 weeks (P (P <0.05). The expression of FAS, CPT-1α, UCP2, PPAR-γ and CD36 in hepatic tissue increased (P <0.05), while the expression of SCD-1, DGAT-1 and GPAT decreased (P <0.05). Compared with WT-HFD group, body weight, epididymal fat tissue weight, organ coefficient, body fat distribution and adipocyte volume in KO-HFD group were significantly decreased (P <0.05), and triglyceride content and liver Tissue fat content was also significantly lower (P <0.05). The gene expression analysis of liver tissue showed that CYP1B1 knockdown could inhibit the expression of FAS, SCD-1, DGAT-1, GPAT and PPAR-γ and CD36 (P <0.05) and promote the expression of CPT-1α and UCP2 ; At the same time, promote the expression of AMPK protein. Conclusion The protective effects of CYP1B1 knockout on nutritional obesity may be related to AMPK regulating the expression of genes related to lipometabolism in liver tissues.