Title Page
Contents
ABBREVIATIONS 11
요약 13
I. INTRODUCTION 16
1. Purpose of study 16
2. Background 19
2.1. Lipid metabolism in the liver 19
2.2. Carbohydrate metabolism in the liver 23
2.3. p-Coumaric acid 25
2.4. High fructose diet and metabolic syndrome 25
2.5. High fructose diet-fed hamster 26
II. MATERIAL AND METHODS 28
1. Animals and experimental design 28
2. Sampling procedure 31
3. Biochemical analysis 31
3.1. Blood glucose analysis 31
3.2. Plasma lipid analysis 31
3.3. Hepatic lipid analysis 32
3.4. Fecal lipid analysis 32
3.5. Plasma AST, ALT analysis 32
3.6. Hepatic enzyme activity analysis 33
4. Histopathological examination 34
5. RNA isolation and quantitative reverse transcription polymerase chain reaction analysis 34
5.1. RNA extraction and cDNA synthesis 34
5.2. Quantitative reverse transcription polymerase chain reaction analysis 35
6. Statistical analysis 37
III. RESULTS 38
1. Effects of p-coumaric acid on food intake, body weight, organ weight, and adipose tissue weight in HFrD-fed hamsters 38
1.1. Food intake, energy intake, body weight, body weight gain and food efficiency ratio 38
1.2. Organ weight and adipose tissue weight 40
2. Effects of p-coumaric acid on levels of blood glucose, plasma insulin and HOMA-IR in HFrD-fed hamsters 41
3. Effects of p-coumaric acid on plasma, hepatic and fecal lipids levels and liver histopathological examination of liver in HFrD-fed hamsters 42
3.1. Plasma lipid profiles 42
3.2. Hepatic lipids contents and histopathological examination 44
3.3. Fecal lipids levels 47
4. Effects of p-coumaric acid on aminotransferases levels in HFrD-fed hamsters 48
5. Effects of p-coumaric acid on lipid metabolism-related enzymes activities and mRNA expression in HFrD-fed hamsters 49
5.1. Hepatic lipid metabolism-related enzyme activity 49
5.2. Effects on lipogenic genes expression in liver 51
5.3. Effects on fatty acid oxidation-related genes expression in liver 53
6. Effects of p-coumaric acid on glucose metabolism-related enzymes activities and mRNA expression in HFrD-fed hamsters 54
6.1. Hepatic glucose metabolism-related enzyme activity 54
6.2. Effects on glucose metabolism-related genes expression in liver 56
IV. DISCUSSION 58
1. p-Coumaric acid ameliorates abnormal plasma and hepatic glucose metabolism in HFrD-fed hamsters 58
2. p-Coumaric acid attenuates dyslipidemia and nonalcoholic fatty liver disease in HFrD-fed hamsters 59
V. CONCLUSION 64
VI. REFERENCE 65
Table 1. Diet ingredient composition 30
Table 2. Primer sequences of genes used for qRT-PCR 36
Table 3. Effects of p-coumaric acid supplementation for 5 weeks on food intake,... 40
Fig. 1. Chemical structure of p-coumaric acid 18
Fig. 2. Lipid metabolism regulatory pathway 22
Fig. 3. Carbohydrate metabolism pathway 24
Fig. 4. Experimental design. 29
Fig. 5. Effects of p-coumaric acid on body weight change in Golden Syrian... 39
Fig. 6. Effects of p-coumaric acid on levels of blood glucose (a), plasma insulin... 41
Fig. 7. Effects of p-coumaric acid on plasma TG (a), TC (b), LDL/VLDL-C (c),... 43
Fig. 8. Effects of p-coumaric acid on liver TG (a) and TC (b) levels in Golden... 45
Fig. 9. Effect of p-coumaric acid on histopathological examinations of liver... 46
Fig. 10. Effects of p-coumaric acid on fecal TG (a) and TC (b) levels in Golden... 47
Fig. 11. Effects of p-coumaric acid on plasma AST (a) and ALT (b) levels in... 48
Fig. 12. Effects of p-coumaric acid on activities of PAP (a), CPT (b) and β-... 50
Fig. 13. Effects of p-coumaric acid on mRNA expression of hepatic ACC (a), FAS (b),... 52
Fig. 14. Effects of p-coumaric acid on mRNA expression of hepatic CPT1... 53
Fig. 15. Effects of p-coumaric acid on glucokinase (a), G6pase (b) and PEPCK... 55
Fig. 16. Effects of p-coumaric acid on mRNA expression of hepatic glucokinase... 57