Table 3.
Comparison of DNA methylation alterations of metabolism-related genes with mammal models of obesity and type 2 diabetes.
| Target gene | Description | Region | Sample type | Major finding | References | |
|---|---|---|---|---|---|---|
| 5′ flanking | Gene body | |||||
| FABP | Liver type fatty acid binding protein | √ | √ | Human adipose | Polyunsaturated and saturated fat overfeeding induce distinct epigenetic changes, including fatty acid binding protein | (58) |
| LPL | Lipoprotein lipase | √ | / | Rat adipose | Maternal prenatal folic acid supplementation programs offspring lipid metabolism by aberrant DNA methylation in LPL gene | (59) |
| ATGL | Adipose triglyceride lipase | √ | / | Rat liver | Maternal prenatal folic acid supplementation programs offspring lipid metabolism by aberrant DNA methylation in ATGL gene | (59) |
| FASN | Fatty acid synthase | √ | √ | Rat liver | High-fat diet induced lipid-synthesizing genes via gene body methylation of FAS and ACC1 | (42) |
| ACC1 | Acetyl-CoA carboxylase 1 | / | √ | Rat liver | High-fat diet induced lipid-synthesizing genes via gene body methylation of FAS and ACC1 | (42) |
| CPT1 | Carnitine palmitoyltransferase 1Ab | √ | √ | Rat liver | High fructose consumption induced DNA methylation in PPARα and CPT1A promoter | (9) |
| FATB | Solute carrier family 27, member 1/4 | / | √ | – | – | – |
| HSL | Hormone sensitive lipase | / | √ | Adipose tissue of metabolic syndrome patients | DNA methylation of LPL was associated with triglyceride concentrations in the metabolic syndrome | (60) |
| CS | Citrate synthase | √ | √ | – | – | – |
| GS | Glycogen synthase | √ | / | – | – | – |
| GK | Glucokinase | √ | / | Rat liver | Obese rats fed with high-fat diet revealed hypermethylation in promoter regions of hepatic gk and pk | (8) |
| PK | Pyruvate kinase | √ | √ | Rat liver | Obese rats fed with high-fat diet revealed hypermethylation in promoter regions of hepatic gk and pk | (8) |
| G6PC | Glucose 6-phosphatase alpha | √ | / | Piglet liver | Betaine supplementation in maternal diet reduced the DNA methylation in G6PC and improved the G6PC mRNA expression | (39) |
| PEPCK1 | Phosphoenolpyruvate carboxykinase 1 | √ | / | Piglet liver | Betaine supplementation in maternal diet improved the DNA methylation of PEPCK1 promoter and diminished the PEPCK1 mRNA expression | (39) |
| PEPCK2 | Phosphoenolpyruvate carboxykinase 2 | √ | √ | – | – | – |
| PFK1 | 6-Phosphofructokinase 1 | / | √ | – | – | – |
| PFK2 | 6-Phosphofructokinase 2 | √ | √ | – | – | – |
| FBP1 | Fructose-1,6-bisphosphatase 1 | / | √ | Human hepatocellular carcinoma and colon cancer | Hypermethylation of FBP1 promoter down-regulated FBP1 expression | (61) |
| INS | Insulin | √ | / | Mouse embryonic stem cell | Ins2 was fully methylated and became demethylated as the cells differentiate into insulin-expressing cells in vitro | (62) |
| IRA | Insulin receptor A | / | √ | Hypothalamus of rat | Insulin receptor promoter is vulnerable to hypermethylation due to overnutrition, probably especially glucose dependent in a dose–response manner | (63) |
| IRB | Insulin receptor B | / | √ | – | – | – |
| IRS | Insulin receptor substrate | / | √ | Human blood | There was no association between IRS-1 promoter methylation and type 2 diabetes between genders | (64) |
| SREBP1 | Sterol regulatory element binding transcription factor 1 | / | √ | Human adipose | The promoter of SREBF1 was hypomethylated under vitamin B12-deficient conditions | (40) |
| IL-6 | Interleukin 6 | / | √ | Peripheral blood mononuclear cells | The methylation status of a single CpG site in the IL6 promoter is related to IL6 mRNA expression and rheumatoid arthritis | (65) |
| TNFα | Tumor necrosis factor α | / | √ | Human adipose | TNF α promoter methylation levels could be used as epigenetic biomarkers concerning response to low-calorie diet | (43) |
| LepR | Leptin receptor | / | √ | – | – | – |
| AdipoR | Adiponectin receptor | √ | / | – | – | – |
| SOCS3 | Suppressor of cytokine signaling 3 | √ | / | Peripheral blood mononuclear cells | DNA methylation of SOCS3 was inversely related with metabolic syndrome | (37) |
| PPARα | Peroxisome proliferator-activated receptors α a | √ | √ | Rat liver | High fructose consumption induces DNA methylation at PPARα and CPT1A promoter | (9) |
| AMPK | 5′-AMP-activated protein kinase | √ | √ | Human blood and mouse muscle | DNA methylation of AMPK gene increased after moderate-endurance exercise in humans and mice | (66) |
| PGC-1α | Peroxisome proliferator-activated receptor gamma coactivator 1 α | √ | √ | Human THP-1 monocytes and rat adipose | Supplementation with saturated fatty acids and elaidic acid induced the hypermethylation of PPARG1 | (25) |