title: Genome-wide hepatic DNA methylation changes in high-fat diet-induced obese mice.
abstract: OBJECTIVE
  A high-fat diet (HFD) induces obesity, which is a major risk factor for cardiovascular disease and cancer, while a calorie-restricted diet can extend life span by reducing the risk of these diseases. It is known that health effects of diet are partially conveyed through epigenetic mechanism including DNA methylation. In this study, we investigated the genome-wide hepatic DNA methylation to identify the epigenetic effects of HFD-induced obesity.
  
  
  METHODS
  Seven-week-old male C57BL/6 mice were fed control diet (CD), calorie-restricted control diet (CRCD), or HFD for 16 weeks (after one week of acclimation to the control diet). Food intake, body weight, and liver weight were measured. Hepatic triacylglycerol and cholesterol levels were determined using enzymatic colorimetric methods. Changes in genome-wide DNA methylation were determined by a DNA methylation microarray method combined with methylated DNA immunoprecipitation. The level of transcription of individual genes was measured by real-time PCR.
  
  
  RESULTS
  The DNA methylation statuses of genes in biological networks related to lipid metabolism and hepatic steatosis were influenced by HFD-induced obesity. In HFD group, a proinflammatoryCasp1(Caspase 1) gene had hypomethylated CpG sites at the 1.5-kb upstream region of its transcription start site (TSS), and its mRNA level was higher compared with that in CD group. Additionally, an energy metabolism-associated geneNdufb9(NADH dehydrogenase 1 beta subcomplex 9) in HFD group had hypermethylated CpG sites at the 2.6-kb downstream region of its TSS, and its mRNA level was lower compared with that in CRCD group.
  
  
  CONCLUSIONS
  HFD alters DNA methylation profiles in genes associated with liver lipid metabolism and hepatic steatosis. The methylation statuses ofCasp1andNdufb9were particularly influenced by the HFD. The expression of these genes in HFD differed significantly compared with CD and CRCD, respectively, suggesting that the expressions ofCasp1andNdufb9in liver were regulated by their methylation statuses.
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: AhRam
authors.initials: A
authors.lastname: Yoon
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Tammen
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.; Research Institute of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
authors.forename: Sung Nim
authors.initials: SN
authors.lastname: Han
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.; Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.; Chaum Life Center, CHA University School of Medicine, Seoul 06062, Korea.
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
keywords: Caspase 1; DNA methylation; NADH dehydrogenase; liver; obesity