母代肥胖对子代肝脏脂代谢和非编码RNA MALAT1的影响

Effect of maternal obesity on offspring liver lipid mechanism and the mechanism of non-coding RNA MALAT1 regulation

目的探讨母代肥胖对子代肝脏脂代谢的影响和非编码RNA转移相关肺腺癌基因转录本1(MALAT1)调控机制。方法采用随机数字表法将雌性C57/BL6小鼠分为2个组,对照组喂养普通饲料,肥胖组喂养高脂饲料。喂养10周后,两组雌鼠分别与雄鼠按2∶1比例交配。两组母鼠产仔后取其雄性子代正常喂养,观察两组子代生长发育。子代8周龄时处死,采用qPCR检测LncRNA MALAT1和代谢相关基因的表达,蛋白印迹检测蛋白表达。结果经过10周的高脂饮食喂养,肥胖组体重和血脂明显高于对照组,差异有统计学意义(P<0.05)。肥胖组子代出生体重明显高于对照组子代,差异有统计学意义(t=2.652,P=0.011);出生第1周肥胖组子代存活率明显低于对照组子代(P=0.002)。两组子代在生长过程中肥胖组子代处于体重较高的趋势,且肥胖组子代TG水平高于对照组子代,差异有统计学意义(t=2.152,P=0.031)。与对照组子代相比,肥胖组子代肝脏组织Srebp1c的mRNA和蛋白表达明显上调,差异均有统计学意义(P<0.05)。相对于对照组子代,肥胖组子代MALAT1表达明显升高,差异有统计学意义(t=7.562,P=0.000)。肥胖组子代MALAT1表达与Srebp1c蛋白表达呈正相关(R2=0.249,P=0.011)。结论母亲肥胖可能是诱发子代成年期肝脏脂质代谢异常的一个高风险因素,非编码RNA MALAT1可能在其中扮演了重要角色。

Objective To investigate the effect of maternal obesity on offspring liver lipid mechanism and the mechanism of non-coding RNA MALAT1 regulation.Methods C57/BL6 mice(8-week-old)were used in this study;control group were fed normal diet and obesity group were fed high-fat diet for 10 weeks.Two groups of females were mated with male mice according to the ratio of 2:1.The offspring of growth curve were observed.The LncRNA MALAT1 and metabolic related gene were determined by qPCR.Protein expression were evaluated by western-blot.Results After 10 weeks of high-fat diet,body weight and blood lipids were significantly increased(P<0.05).The birth weight obese offspring was greater than that of control offspring(t=2.652,P=0.011).The first week survival rate of obese offspring was lower than the control group(P=0.002).The offspring of obese mice had a tendency to be overweight during their growth and the offspring of obese mice had higher TG(t=2.152,P=0.031).Compared with the control offspring,the obese offspring mRNA and protein expression of Srebp1 c were significantly up-regulated(P<0.05).Compared with control offspring,the expression of MALAT1 in obese offspring was significantly increased(t=7.562,P=0.000).There was a positive correlation between MALAT1 expression and Srebp1 c protein expression in obesity offspring(R2=0.249,P=0.011).Conclusion Maternal obesity might be a high-risk factor of liver lipid metabolism disturbance in male offspring and non-coding RNA MALAT1 might play an important role.