肥胖小鼠DNA甲基化改变以及n-3多不饱和脂肪酸的影响作用

Changes in global DNA methylation and the effects of n-3 polyunsaturated fatty acids in diet-induced obese mice

【目的】探讨肥胖状态下脂肪组织基因组DNA甲基化及甲基转移酶表达改变以及n-3多不饱和脂肪酸(n-3PUFAs)的影响作用。【方法】使用30只3～4周龄C57BL/6J雄性小鼠,随机分为3组,每组10只。小鼠分别给予两种高脂饲料(脂肪含量为34.9%,供能比为60%)-n-6PUFAs(脂肪来源于葵花籽油)饲料和n-3PUFAs(脂肪来源于鱼油)饲料喂养14周;以正常脂饲料(脂肪含量为4.3%,供能比为10%)(脂肪来源于葵花籽油)为对照。喂养结束后对小鼠脂肪组织基因组DNA总甲基化以及甲基转移酶(DNMTs)进行测定。【结果】与正常脂饲料喂养小鼠相比,两组高脂饲料诱导肥胖小鼠的脂肪组织DNA总甲基化程度均明显升高,但n-3PUFAs高脂饲料组升高的程度显著低于n-6PUFAs组。n-6PUFAs高脂饲料诱导肥胖小鼠的脂肪组织DNMT1、DNMT3a和DNMT3b的表达均显著高于正常脂饲料组小鼠,而n-3PUFAs高脂饲料喂养小鼠脂肪组织中这3种酶的表达无变化。【结论】肥胖状态下脂肪组织基因组DNA甲基化程度升高;鱼油n-3PUFAs具有抑制DNA甲基化的作用。

【Objective】 The aim of this study is to investigate the changes in global DNA methylation and the effects of n-3 polyunsaturated fatty acids（n-3 PUFAs） in obesity. 【Methods】 Thirty 3-4 week-old C57BL/6J male mice were randomly divided into 3 groups.Mice were fed with two types of high-fat diet（containing 34.9% fat providing 60% of total energy） with n-6 PUFAs（fat from sunflower oil） and n-3 PUFAs（fat from fish oil） respectively to induce obesity for 14 weeks,with a normal-fat diet（4.3% fat providing 10% of total energy）（fat from sunflower oil） as lean control.After fasted for 12 hours,mice were sacrificed and the epididymal fat was collected.Global DNA methylation and the expression of DNA methyltransferases（DNMTs） from the adipose tissue were measured by enzyme-linked immunosorbent assay. 【Results】 As compared to the lean control mice,the rates of global DNA methylation in adipose tissue were significantly increased in the two groups of diet-induced obese（DIO） mice.If the two groups of DIO mice were compared,the n-3 PUFAs in diets had inhibitory effects on the global DNA methylation.The expressions of DNMT1,DNMT3a and DNMT3b in the adipose tissue were higher in DIO mice fed the n-6 PUFAs diet compared to the normal-fat diet,whereas no changes were shown in the expression of these DNMTs in DIO mice fed the n-3 PUFAs diet. 【Conclusion】 The global DNA methylation in the adipose tissue of obesity increases and dietary fish oil n-3 PUFAs have inhibitory effects on DNA methylation.