文献类型： 外文期刊

作者： Feng, Y. ¹ ; Cirera, S. ³ ; Tasoz, E. ³ ; Liu, Y. ¹ ; Olsen, L. H. ³ ; Christoffersen, B. O. ⁴ ; Pedersen, H. D. ³ ; Ludv ¹ ;

作者机构： 1.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Minist Agr,Shenzhen Branch, Genome Anal Lab,Guangdong Lab Lingnan Modern Agr, Shenzhen, Peoples R China

2.South China Agr Univ, Coll Life Sci, Guangdong Prov Key Lab Prot Funct & Regulat Agr O, Guangzhou, Peoples R China

3.Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet & Anim Sci, Frederiksberg, Denmark

4.Novo Nordisk AS, Global Drug Discovery, Malov, Denmark

5.Danish Med Agcy, Med Evaluat & Biostat, Copenhagen, Denmark

关键词： epigenetics; promoter DNA methylation; diet intervention; obesity; metabolism

期刊名称：FRONTIERS IN GENETICS （ 影响因子：3.258； 五年影响因子：4.005 ）

ISSN：

年卷期： 2021 年 12 卷

页码：

收录情况： SCI

摘要： Objective: Environmental factors can influence obesity by epigenetic mechanisms. The aim of this study was to investigate obesity-related epigenetic changes and the potential for reversal of these changes in the liver of Gottingen minipigs subjected to diet interventions. Methods: High-throughput liquid hybridization capture-based bisulfite sequencing (LHC-BS) was used to quantify the methylation status of gene promotor regions in liver tissue in three groups of male castrated Gottingen minipigs: a standard chow group (SD, N = 7); a group fed high fat/fructose/cholesterol diet (FFC, N = 10) and a group fed high fat/fructose/cholesterol diet during 7 months and reversed to standard diet for 6 months (FFC/SD, N = 12). Expression profiling by qPCR of selected metabolically relevant genes was performed in liver tissue from all pigs. Results: The pigs in the FFC diet group became morbidly obese. The FFC/SD diet did not result in a complete reversal of the body weight to the same weight as in the SD group, but it resulted in reversal of all lipid related metabolic parameters. Here we identified widespread differences in the patterning of cytosine methylation of promoters between the different feeding groups. By combining detection of differentially methylated genes with a rank-based hypergeometric overlap algorithm, we identified 160 genes showing differential methylation in corresponding promoter regions in the FFC diet group when comparing with both the SD and FFC/SD groups. As expected, this differential methylation under FFC diet intervention induced de-regulation of several metabolically-related genes involved in lipid/cholesterol metabolism, inflammatory response and fibrosis generation. Moreover, five genes, of which one is a fibrosis-related gene (MMP9), were still perturbed after diet reversion. Conclusion: Our findings highlight the potential of exploring diet-epigenome interactions for treatment of obesity.