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

中国儿童保健杂志 ›› 2012, Vol. 20 ›› Issue (4): 333-335.

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

申文雯,樊超男,夏露露,王翠,董华,齐可民

首都医科大学附属北京儿童医院、北京市儿科研究所,儿科学国家重点学科,教育部儿科重大疾病研究重点实验室,北京 100045

收稿日期:2011-12-04 发布日期:2012-04-06 出版日期:2012-04-06
通讯作者: 齐可民,E-mail:qkm731@sohu.com
作者简介:申文雯,女,硕士生,研究方向为儿童营养
基金资助:
荷兰Nutricia Research Foundation(2009-15,2010-E4)

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

SHEN Wen-wen,FAN Chao-nan,XIA Lu-lu,WANG Cui,DONG Hua,QI Ke-min

Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics,Capital Medical University,Ministry of Education,Beijing Pediatric Research Institute,Beijing Children's Hospital,Capital Medical University,Beijing 100045,China

Received:2011-12-04 Online:2012-04-06 Published:2012-04-06

摘要/Abstract

摘要： 【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-3 PUFAs)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-6 PUFAs(脂肪来源于葵花籽油)饲料和n-3 PUFAs(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-3 PUFAs高脂饲料组升高的程度显著低于n-6 PUFAs组。n-6 PUFAs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-3 PUFAs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-3 PUFAs具有抑制DNA甲基化的作用。

关键词: DNA甲基化, DNA甲基转移酶, n-3多不饱和脂肪酸, 肥胖, 小鼠

Abstract: 【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.

Key words: DNA methylation, DNA methyltransferases, n-3 polyunsaturated fatty acids, obesity, mice

中图分类号:

R153.2

申文雯,樊超男,夏露露,王翠,董华,齐可民. 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[J]. 中国儿童保健杂志, 2012, 20(4): 333-335.

SHEN Wen-wen,FAN Chao-nan,XIA Lu-lu,WANG Cui,DONG Hua,QI Ke-min. Changes in global DNA methylation and the effects of n-3 polyunsaturated fatty acids in diet-induced obese mice[J]. journal1, 2012, 20(4): 333-335.

参考文献

[1] Dolinoy DC,Weidman JR,Jirtle RL.Epigenetic gene regulation:linking early developmental environment to adult disease[J].Reprod Toxicol,2007,23(3):297-307.
[2] Stover PJ,Caudill MA.Genetic and epigenetic contributions to human nutrition and health:managing genome-diet interactions[J].J Am Diet Assoc,2008,108(9):1480-1487.
[3] Herrera BM,Keildson S,Lindgren CM.Genetics and epigenetics of obesity[J].Maturitas,2011,69(1):41-49.
[4] Buckley JD,Howe PR.Anti-obesity effects of long-chain omega-3 polyunsaturated fatty acids[J].Obes Rev,2009,10:648-659.
[5] Ailhaud G,Massiera F,Weill P,et al.Temporal changes in dietary fats:role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity [J].Prog Lipid Res,2006,45(3):203-236.
[6] Marti A,Ordovas J.Epigenetics lights up the obesity field[J].Obes Facts,2011,4(3):187-190.
[7] Pinnick KE,Karpe F.DNA methylation of genes in adipose tissue[J].Proc Nutr Soc,2011,70(1):57-63.
[8] Cordero P,Campion J,Milagro FI,et al.Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet[J].J Physiol Biochem,2011,67(3):463-4670.
[9] 刘新丽,樊超男,田春雨,等.饮食诱导肥胖小鼠瘦素及受体基因启动子甲基化探讨[J].中国儿童保健杂志,2011,19(12):1096-1099.
[10] Gabory A,Attig L,Junien C.Developmental programming and epigenetics[J].Am J Clin Nutr,2011,94(6S):1943-1952.
[11] Burdge GC,Lillycrop KA.Bridging the gap between epigenetics research and nutritional public health interventions [J].Genome Med,2010,2(11):80-86.
[12] McGowan PO,Meaney MJ,Szyf M.Diet and the epigenetic (re)programming of phenotypic differences in behavior[J].Brain Res,2008,1237:12-24.
[13] Kamei Y,Suganami T,Ehara T.Increased expression of DNA methyltransferase 3a in obese adipose tissue:studies with transgenic mice[J].Obesity (Silver Spring),2010,18(2):314-321.
[14] Wang X,Zhu H,Snieder H.Obesity related methylation changes in DNA of peripheral blood leukocytes[J].BMC Med,2010,8:87-90.
[15] Vel Szic KS,Ndlovu MN,Haegeman G,et al.Nature or nurture:let food be your epigenetic medicine in chronic inflammatory disorders[J].Biochem Pharmacol,2010,80(12):1816-1832.
[16] Kulkarni A,Dangat K,Kale A,et al.Effects of altered maternal folic acid,vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats[J].PLoS One,2011,6:e17706.