Title Page
Contents
LIST OF ABBREVIATION 12
ABSTRACT 14
Ⅰ. Introduction 17
Ⅱ. Literature Review 21
1. Prevalence and definition of Non-alcoholic fatty liver disease (NAFLD) 21
1) Lipid m m etabolism pathway in liver 25
2) Inflammation pathway in liver 27
2. Pathogenesis of NAFLD 23
3. Blackcurrant (Ribes nigrum L.) 29
1) Bioactive compounds in blackcurrant 30
2) Physiological effects of bioactive compounds from blackcurrant 31
Ⅲ. Materials and Methods 34
1. Experimental Scheme 34
2. Methods of study 37
2.1. Animals and diets 37
2.2. Preparation of sample 38
2.3. Total polyphenol contents, total flavonoid contents, and anthocyanidins contents determination 38
2.4. Measurement of body weight, food Intake, and drink Intake 40
2.5. Blood and tissue collection 41
2.6. Biochemical assessment of serum 42
2.7. Hepatic triglyceride contents 46
2.8. Histological analysis of liver 46
2.9. Western blot analysis 47
2.10. Real-time quantitative reverse transcription PCR analysis 48
2.11. Statistical analysis 50
Ⅳ. Results 51
1. Total polyphenol contents, total flavonoid contents, and anthocyanin contents 51
2. Food Intake, drink Intake, food Efficiency Ratio(FER), and body weight 53
3. Organ weight coefficients 60
4. Serum glucose level 64
5. Serum lipid profiles analysis 66
6. Serum liver function index analysis 71
7. Serum TNF-α level analysis 73
8. Hepatic triglyceride content 75
9. Hepatic histological result 77
10. Lipid accumulation related protein expression level 78
11. Inflammation related protein expression level 87
10. Fatty acid oxidation related gene expression level 92
Ⅴ. Discussion 95
Ⅵ. SUMMARY AND CONCLUSION 102
Ⅶ. REFERENCE 104
ABSTRACT IN KOREAN 118
Table 1. Primer sequences for mRNA expression 49
Table 2. Total polyphenol content, total flavonoid content, cyanidin-3-O-glucoside, and cyanidin-3-O-rutinoside 52
Table 3. Food intake, FER(%), drink intake, and fructose intake 54
Table 4. Initial body weight, final body weight, and body weight gain 57
Table 5. Organ weight coefficients 61
Table 6. Serum glucose level 65
Table 7. Serum triglyceride, serum total cholesterol, serum HDL-C, serum LDL-C, and serum VLDL-C 67
Table 8. Atherogenic index of plasma and cardiovascular risk ratio 70
Table 9. Serum AST level and serum ALT level 72
Table 11. Hepatic triglyceride content 76
Table 12. Lipid accumulation related protein expression level 79
Table 13. Inflammation related protein expression level 88
Table 14. Fatty acid oxidation related gene expression level 93
Figure 1. Chemical structures of 4 primary anthocyanins 33
Figure 2. Experimental design 36
Figure 3. Food intake, FER (%), drink intake, and fructose intake 55
Figure 4. Initial body weight, final body weight, and body weight gain 58
Figure 5. Body weight change of each group 59
Figure 6. Organ weight coefficients 62
Figure 7. Serum glucose level 65
Figure 8. Serum triglyceride, serum total cholesterol, serum HDL-C, serum LDL-C, and serum VLDL-C 68
Figure 9. Atherogenic index of plasma and cardiovascular risk ratio 70
Figure 10. Serum AST level and serum ALT level 72
Figure 11. Serum TNF-α level 74
Figure 12. Hepatic triglyceride content 76
Figure 13. Hepatic histological result 77
Figure 14. Protein expression of AMPK, p-AMPK, and p-AMPK/AMPK in liver 80
Figure 15. Protein expression of SREBP1c in liver 82
Figure 16. Protein expression of FASN in liver 84
Figure 17. Protein expression of ACC, p-ACC, and p-ACC/ACC in Liver of each group 86
Figure 18. Protein expression of NF κB(p65), p-NF κB(p-p65), and p-NF κB(p-p65)/NF κB(p65) in liver 89
Figure 19. Protein expression of IkB in liver 91
Figure 20. Fatty acid oxidation related gene expression level 94
Figure 21. Mechanism of ameliorating lipid accumulation and inflammatory responses by supplementation of blackcurrant extract in a rat model of NAFLD 101