[보고서]대사성 스트레스 제어를 위한 전통천연물의 MC/MT 효능 평가용 바이오마커 개발 및 질병예방 맞춤형 소재 도출

대사성 스트레스 제어를 위한 전통천연물의 MC/MT 효능 평가용 바이오마커 개발 및 질병예방 맞춤형 소재 도출
Development of metabolic stress-responsive multiomics biomarkers to evaluate efficacy of the traditional bioactive materials with MC/MT for disease prevention 원문보기

보고서 정보
주관연구기관	경북대학교 KyungPook National University
보고서유형	1단계보고서
발행국가	대한민국
언어	한국어
발행년월	2015-11
과제시작연도	2014
주관부처	미래창조과학부 Ministry of Science, ICT and Future Planning
등록번호	TRKO201500019551
과제고유번호	1711019237
사업명	바이오·의료기술개발
DB 구축일자	2016-03-19
키워드	바이오마커.전통천연물.다중화합물.다중타깃(작용점).비만.지방간.유효성.대사성 질환.염증질환.Biomarker.Tranditional muticompound.Muti-compound.Muti-targets.Obesity.Fatty liver.Efficacy.Metabolic disease.Inflammatory disease.
DOI	https://doi.org/10.23000/TRKO201500019551

초록 ▼

• 대사성 스트레스 관련 질환에 반응성을 나타내는 전통천연물 소재 및 처방제의 지표성분과 in vitro 기초자료를 확보하고 in vivo 실험 설계를 하였음.
• 식이성 대사증후군 모델에서 비만과 비만 유래의 지방간과 염증반응으로 인한 Phenotype과 전사체(mRNA seqeuencing) 바이오마커의 변화를 분석하였음.
• 비만과 대사성질환에서 녹차추출물, 태음조위탕, 방풍통성산, 길경, 내복자, 비타민나무 및 관련 유효성분의 보충이 간과 말초조직 간의 crosstalk에 미치는 영향을 규명하였음.
• 표적장

Abstract ▼

Ⅱ. Objectives
• To search potential multi-omics biomarkers in disease animal model that is induced by high-fat metabolic stress
• To elucidate how the multi-compounds in traditional medicinal prescription act on multi-targets to alleviate the pathogenesis of obesity and its comorbidities (non-alcoholic fatty liver disease and inflammatory disease etc) induced via metabolic stress
• To find hard-claim pharma-medicinal materials using multi-omics biomarkers
Ⅲ. Contents of research
• To profile the indicative compounds in traditional medicinal prescription via bioinformatic search
• To identify phenotypic changes of obesity and inflammatory disease in diet-induced obesity and to analyze interaction among multi-tissues such as liver, adipose tissue, muscle, intestine and lung
• To analyze biomarkers and gene profile by mRNA sequencing affected by high-fat diet and MC in target tissue
• To elucidate function of biomarkers and genes involved in the regulation of metabolic disease
• To identify and validate multi-biomarkers associated with metabolic disease using multiple omics database
• To analyze the cell signaling/transcriptome/physiological response in efficacy of multicompounds
• To validate the responsiveness of traditional herbal medicinal prescription based on gene profile of individual animal and analyze the corelation between transcriptomic profiles and phenotypes
• To design and develop hard-claim pharma materials using multiomics biomarkers
• This result can be useful for evaluation elucidantion of potential mechanism of multicompounds on high –fat induced metabolic disease.
• Multi-biomarkers identified via for high throughout technology can be applied as efficacy parameters for bioactive multicompounds.
• The biomarkers and genes identified in this study can be applied for development of personalized medicinal drug or medicinal dietary supplements.
Ⅳ. Expected contribution of research
• This result can be useful for evaluation of effects and potential mechanism of multicompounds on metabolic disease in animals.
• Multi-biomarkers identified for metabolic disease in diet-induced obesity can be used as efficacy parameters for bioactive multicompounds.
• The biomarkers and genes identified in this study can be applied for development of personalized medicinal drug or medicinal dietary supplements.

목차 Contents

표지 ... 1
제 출 문 ... 2
보고서 요약서 ... 3
요 약 문 ... 4
S U M M A R Y ... 18
C O N T E N T S ... 20
목차 ... 21
제 1 장 연구개발과제의 개요 ... 22
제 1절 연구개발의 목적 ... 22
제2절 연구개발의 필요성 ... 22
제 2 장 국내외 기술개발 현황 ... 27
제1절 국내 연구현황 ... 27
제2절 국외 연구현황 ... 31
제 3 장 연구개발수행 내용 및 결과 ... 33
제 1절 연구수행 방법 및 내용 ... 34
제 2절 연구결과 ... 62
제 4 장 목표달성도 및 관련분야에의 기여도 ... 299
제 1 절 연구목표의 달성도 ... 299
제 2 절 관련분야에의 기여도 ... 300
제 5 장 연구개발결과의 활용계획 ... 302
제 6 장 연구개발과정에서 수집한 해외과학기술정보 ... 304
제 7 장 연구시설 · 장비 현황 ... 305
제 8 장 참고문헌 ... 306
끝페이지 ... 309

표/그림 (201)

표 Figure 4. Changes of mean body weight and blood glucose level in C57BL/6J mice fed 10% kcal fat diet or 60 % kcal fat diet
표 Figure 5. Oral Glucose Tolerance Test (OGTT) of C57BL/6J fed 10% kcal fat diet or 60% kcal fat diet
표 Figure 6. In vitro co-culture model
표 Figure 7. 비타민 나무(A)와 열매(B,C), 씨(D), 재배분포
표 Figure 8. Change of body weight for 12 weeks of obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fed fat diet
표 Figure 9. Change of plasma triglyceride and total-cholesterol concentrations of obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 10. Change of fasting blood glucose concentration, glucose tolerance and plasma insulin and glucagon concentrations in obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet
표 Figure 11. Hepatic triglycerid and cholesterol contents in obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 12. The fecal lipids excretion of obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 13. Plasma adipokine levels in obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 14. GIP and GLP-1 concentrations in obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 15. Concentration of (A) TNF-α, (B) MCP-1, (C) IFN-γ, (D) IL-6, (E) IL-10 and (F) PAI-1 levels in obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 16. Hepatic and white adipose tissue morphology in obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks (× 200)
표 Figure 17. GOP and GPT activities in obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 18. The hepatic HMGCR and ACAT activities of obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 19. The hepatic glycogen content and glucose regulating enzymes activities of obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 20. The hepatic antioxidant enzymes activities of obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 21. The erythrocyte antioxidant enzymes activities of obese-prone and obese-resistant C57BL/6J mice whose phenotype was observed after feeding high-fat diet for 12 weeks
표 Figure 22. Heatmap of top 20 most up-regulated and down-regulated genes in the epididymal white adipose tissue in high fat diet-obesity prone group compared to the normal diet group
표 Figure 23. 1H NMR spectrum of liver polar extract. 1: Isoleucine, 2: Leucine, 3: Valine, 4: Propylene glycol, 5: 3-Hydroxybutyrate, 6: Lactate, 7: Threonine, 8: Alanine, 9: Acetate, 10: Glutamate, 11: Glutamine, 12: Methionine, 13: Glutathione, 14: Acetone, 15: Succinate, 16: Malate, 17: Dimethylamine, 18: Creatine, 19: Lysine, 20: Choline, 21: Betaine, 22: Taurine, 23: Glucose, 24: Methanol, 25: Glycine, 26: Maltose, 27: Inosine + Adenosine, 28: Ascorbate, 29: Mannose, 30: Uracil, 31: Fumarate, 32: Tyrosine, 33: Histidine, 34: Phenylalanine, 35: Niacinamide, 36: Xanthosine, 37: Uridine, 38: Xanthine, 39: Hypoxanthine, 40: Oxypurinol, 41: Formate, 42: AMP, 43: ADP, 44: ATP
표 Figure 24. UPLC/Q-TOF spectrum of liver lipid extract - Positive mode
표 Figure 25. UPLC/Q-TOF spectrum of liver lipid extract - Negative mode
표 Figure 26. UPLC/Q-TOF spectrum of plasma lipid extract - Positive mode
표 Figure 27. UPLC/Q-TOF spectrum of plasma lipid extract - Negative mode
표 Figure 28. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots obtained from the 1H NMR spectra of liver polar extract for global analysis, which is demonstrating a clear differentiation among the groups; (A) PCA score plot for HFD-OP, HFD-OR, ND; (B) PLS-DA score plot for HFD-OP, HFD-OR, ND; (C) PCA score plot for HFD-OP, HFD-OR; (D) PLS-DA score plot for HFD-OP, HFD-OR
표 Figure 29. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots obtained from the 1H NMR spectra of liver polar extract for targeted analysis, which is demonstrating a clear differentiation among the groups; (A) PCA score plot for HFD-OP, HFD-OR, ND; (B) PLS-DA score plot for HFD-OP, HFD-OR, ND; (C) PCA score plot for HFD-OP, HFD-OR; (D) PLS-DA score plot for HFD-OP, HFD-OR
표 Figure 30. VIP plot obtained from the 1H NMR spectra of liver polar extract. VIP values of glycine, choline, taurine, 3-hydroxybutyrate, glutamine, acetone, methionine, hypoxanthine, tyrosine, oxypurinol, histidine, AMP, phenylalanine, threonine, valine, xanthine, alanine, uracil, leucine, ATP, inosine, glucose is higher than 1
표 Figure 31. Quantification of significant difference of polar metabolites in liver
표 Figure 32. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots obtained from the UPLC/Q-TOF MS spectra of liver lipid extract for global analysis, which is demonstrating a clear differentiation among the groups ; (A) PCA score plot for HFD-OP, HFD-OR, ND in positive mode of UPLC/Q-TOF MS; (B) PCA score plot for HFD-OP, HFD-OR, ND in negative mode of UPLC/Q-TOF MS; (C) PLS-DA score plot for HFD-OP, HFD-OR, ND in positive mode of UPLC/Q-TOF MS; (D) PLS-DA score plot for HFD-OP, HFD-OR, ND in negative mode of UPLC/Q-TOF MS; (E) PCA score plot for HFD-OP, HFD-OR in positive mode of UPLC/Q-TOF; (F) PCA score plot for HFD-OP, HFD-OR in negative mode of UPLC/Q-TOF MS; (G) PLS-DA score plot for HFD-OP, HFD-OR in positive mode of UPLC/Q-TOF MS; (H) PLS-DA score plot for HFD-OP, HFD-OR in negative mode of UPLC/Q-TOF MS
표 Figure 33. Heatmap of increased lipid metabolites(A) and decreased lipid metabolites(B) in liver
표 Figure 34. Lipidomic alteration of PC and TG class in liver
표 Figure 35. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots obtained from the UPLC/Q-TOF MS spectra of plasma lipid extract for global analysis, which is demonstrating a clear differentiation among the groups; (A) PCA score plot for HFD-OP, HFD-OR, ND in positive mode of UPLC/Q-TOF MS; (B) PCA score plot for HFD-OP, HFD-OR, ND in negative mode of UPLC/Q-TOF MS; (C) PLS-DA score plot for HFD-OP, HFD-OR, ND in positive mode of UPLC/Q-TOF MS; (D) PLS-DA score plot for HFD-OP, HFD-OR, ND in negative mode of UPLC/Q-TOF MS; (E) PCA score plot for HFD-OP, HFD-OR in positive mode of UPLC/Q-TOF MS; (F) PCA score plot for HFD-OP, HFD-OR in negative mode of UPLC/Q-TOF MS; (G) PLS-DA score plot for HFD-OP, HFD-OR in positive mode of UPLC/Q-TOF MS; (H) PLS-DA score plot for HFD-OP, HFD-OR in negative mode of UPLC/Q-TOF MS
표 Figure 36. Heatmap of increased lipid metabolites(A) and decreased lipid metabolites(B) in liver
표 Figure 37. Lipidomic alteration of PC and TG class in plasma
표 Figure 38. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots obtained from the 1H NMR spectra of urine for global analysis, which is demonstrating a clear differentiation among the groups; (A) PCA score plot for HFD-OP, HFD-OR, ND ; (B) PLS-DA score plot for HFD-OP, HFD-OR, ND ; (C) PCA score plot for HFD-OP, HFD-OR (D) PLS-DA score plot for HFD-OP, HFD-OR
표 Figure 39. Weekly changes on body weight in C57BL/6J mice fed high-fat diet with traditional prescription medicine for 12 weeks
표 Figure 40. Effect of traditional prescription medicine for 12 weeks on body weight gain, energy intake and FER in C57BL/6J mice fed high-fat diet
표 Figure 41. Effect of traditional prescription medicine for 12 weeks on organ weights in C57BL/6J mice fed high-fat diet
표 Figure 42. Effect of traditional prescription medicine for 12 weeks on adipose tissue weights in C57BL/6J mice fed high-fat diet
표 Figure 43. Weekly changes on plasma total-cholesterol in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 44. Weekly changes on plasma triglyceride in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 45. Effect of traditional medicinal prescription for 12 weeks on the fecal lipids excretion in C57BL/6J mice fed high-fat diet
표 Figure 46. Effect of traditional medicinal prescription for 12 weeks on fasting blood glucose, plasma insulin and glucagon concentrations in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 46. Effect of traditional medicinal prescription for 12 weeks on fasting blood glucose, plasma insulin and glucagon concentrations in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 47. Effect of traditional medicinal prescription for 12 weeks on hepatic triglyceride and cholesterol concentrations in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 48. Effect of traditional medicinal prescription for 12 weeks on plasma adipokine levels in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 49. Effect of traditional medicinal prescription for 12 weeks on plasma GIP and GLP-1 levels in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 50. Effect of traditional medicinal prescription for 12 weeks on plasma adipokine levels in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 51. Hepatic and white adipose tissue morphology in C57BL/6J mice fed high-fat diet (× 200)
표 Figure 51. Hepatic and white adipose tissue morphology in C57BL/6J mice fed high-fat diet (× 200)
표 Figure 52 Effect of traditional medicinal prescription for 12 weeks on GOT and GPT activities in C57BL/6J mice fed high-fat diet with traditional medicinal prescription for 12 weeks
표 Figure 53. Effect of traditional medicinal prescription for 12 weeks on the hepatic HMGCR and ACAT activities in C57BL/6J mice fed high-fat diet
표 Figure 54. Effect of traditional medicinal prescription for 12 weeks on the hepatic glycogen content and glucose regulating enzymes activities in C57BL/6J mice fed high-fat diet
표 Figure 55. The numbers of common genes in the epididymal white adipose tissue in GH, BH and TH groups compared to the high-fat diet group
표 Figure 56. The numbers of common genes in the liver in GH, BH and TH groups compared to the high-fat diet group
표 Figure 57. The numbers of common genes in the muscle in GH, BH and TH groups compared to the high-fat diet group
표 Figure 58. The numbers of common genes in the hypothalamus in GH, BH and TH groups compared to the high-fat diet group
표 Figure 59. The top-ranked adipocyte canonical pathway list in response to green tea extract supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 60.. The top-ranked adipocyte canonical pathway list in response to Bangpungtongsungsan supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 61. The top-ranked adipocyte canonical pathway list in response to Bangpungtongsungsan supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 62. The top-ranked adipocyte canonical pathway list in response to Taeeumjowuitang supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 63 The network 1 of top-ranked IPA generated network and focus molecules of traditional medicinal prescription-responsive adipocyte genes compared to the high-fat control diet in C57BL/6J mice
표 Figure 64. The network 2 of top-ranked IPA generated network and focus molecules of traditional medicinal prescription-responsive adipocyte genes compared to the high-fat control diet in C57BL/6J mice
표 Figure 65. The top-ranked hepatic canonical pathway list in response to green tea extract supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 66. The top-ranked hepatic canonical pathway list in response to Bangpungtongsungsan supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 67. The top-ranked hepatic canonical pathway list in response to Taeeumjowuitang supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 68. The network 1 of top-ranked IPA generated network and focus molecules of traditional medicinal prescription-responsive hepatic genes compared to the high-fat diet in C57BL/6J mice
표 Figure 69. The network 2 of top-ranked IPA generated network and focus molecules of traditional medicinal prescription-responsive hepatic genes compared to the high-fat diet in C57BL/6J mice
표 Figure 70. The top-ranked muscular canonical pathway list in response to green tea extract supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 71. The top-ranked muscular canonical pathway list in response to Bangpungtongsungsan supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 72. The top-ranked muscular canonical pathway list in response to Taeeumjowuitang supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 73. The network 1 of top-ranked IPA generated network and focus molecules of traditional medicinal prescription responding muscular genes compared to the high-fat diet in C57BL/6J mice
표 Figure 74. The top-ranked hypothalamic canonical pathway list in response to green tea extract supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 75. The top-ranked hypothalamic canonical pathway list in response to Bangpungtongsungsan supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 76. The top-ranked hypothalamic canonical pathway list in response to Taeeumjowuitang supplement action in high-fat diet-fed C57BL/6J mice
표 Figure 77. The network 1 of top-ranked IPA generated network and focus molecules of traditional medicinal prescription responding hypothalamic genes compared to the high-fat diet in C57BL/6J mice
표 Figure 78. Effect of green tea extract on transcriptional pattern related with adipocytokine signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 79. Effect of green tea extract on transcriptional pattern related with insulin signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 80. Effect of green tea extract on transcriptional pattern related with AMPK sinaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 81. Effect of Bangpungtongsungsan on transcriptional pattern related with adipocytokine signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 82. Effect of Bangpungtongsungsan on transcriptional pattern related with insulin signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 83. Effect of Bangpungtongsungsan on transcriptional pattern related with PPAR signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 84. Effect of Bangpungtongsungsan on transcriptional pattern related with AMPK signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 85. Effect of Taeeumjowuitang on transcriptional pattern related with oxidiative phosphorylation in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 86. Effect of Taeeumjowuitang transcriptional pattern related with PPAR signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 87. Effect of Taeeumjowuitang on transcriptional pattern related with AMPK signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 88. Effect of Taeeumjowuitang on transcriptional pattern related with inflammatory response in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 89. Effect of green tea extract on transcriptional pattern related with oxidiative phosphorylation in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 90. Effect of green tea extract on transcriptional pattern related with ECM-receptor interaction in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 91. Effect of green tea extract on transcriptional pattern related with cytokine-cytokine receptor interaction in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 92. Effect of Bangpungtongsungsan on transcriptional pattern related with ECM-receptor interaction in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet.
표 Figure 93. Effect of Bangpungtongsungsan on transcriptional pattern related with PPAR signaling pathway C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 94. Effect of Bangpungtongsungsan on transcriptional pattern related with oxidiative phosphorylation in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 95. Effect of Taeeumjowuitang on transcriptional pattern related with ECM-receptor interaction in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet.
표 Figure 96. Effect of Taeeumjowuitang on transcriptional pattern related with inflammatory response in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 97. Effect of green tea extract on transcriptional pattern related with PPAR signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet.
표 Figure 98. Effect of green tea extract on transcriptional pattern related with oxidiative phosphorylation in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 99. Effect of green tea extract on transcriptional pattern related with AMPK signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 100. Effect of green tea extract on transcriptional pattern related with AMPK signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 101. Effect of green tea extract on transcriptional pattern related with insulin signaling pathway in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet.
표 Figure 102. Effect of green tea extract on transcriptional pattern related with oxdiative phosphorylation in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 103. Effect of green tea extract on transcriptional pattern related with oxdiative phosphorylation in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 104. Effect of Bangpungtongsungsan on transcriptional pattern related with PPAR signaling pathway C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet.
표 Figure 105. Effect of Bangpungtongsungsan on transcriptional pattern related with oxdiative phosphorylation in C57BL/6J mice fed high fat diet. Red color indicates up-regulation and green is down-regulation to high-fat diet
표 Figure 106. Principal component analysis (PCA) score scatter plots obtained from the 1H NMR spectra of liver polar extract for global analysis, which is demonstrating a clear differentiation among the groups
표 Figure 107. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots obtained from the 1H NMR spectra of liver polar extract for targeted analysis, which is demonstrating a clear differentiation among the groups; (A) PCA score plot for HFD, GH, BH, TH; (B) PLS-DA score plot for HFD, GH, BH, TH
표 Figure 108. Quantification of significant difference of polar metabolites in liver
표 Figure 109. Partial least squares-discriminant analysis (PLS-DA) 3D score scatter plots obtained from the UPLC/Q-TOF MS spectra of liver lipid extract for global analysis, demonstrating a clear differentiation among the groups
표 Figure 110. Venn diagram of significant difference of hepatic lipid metabolites in GH, BH and TH groups compared to the high-fat diet group
표 Figure 111. Quantification of significant difference of polar metabolites in liver
표 Figure 112. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) score scatter plots obtained from the 1H NMR spectra of 1H NMR spectra of urine for global analysis, which is demonstrating a clear differentiation among the groups; (A) PCA score plot for HFD, GH, BH, TH; (B) PLS-DA score plot for HFD, GH, BH, TH
표 Figure 113. 2D gel images of up/down-regulated proteins in WAT
표 Figure 113. 2D gel images of up/down-regulated proteins in WAT
표 Figure 114. Comparison of expression patterns of obesity-related proteins between OP and ND/OR/OP/TH time. (A) Up-regulated and (B) down-regulated protein in OP mice
표 Figure 115. Differentially regulated adipogenic factors in WAT as deternined by inmmunoblot analysis
표 Figure 116. Networks generated by Ingenuity Pathway Analysis using up-or-down-regulated pretein in response to HFD and TH treatment
표 Figure 117. Weekly changes on body weight in C57BL/6J mice fed high-fat diet with traditional prescription medicine for 12 weeks in repeated animal feeding
표 Figure 118. Effect of traditional medicinal prescription for 12 weeks on body weight, body weight gain, food intake and FER in C57BL/6J mice fed high-fat diet in repeated animal feeding
표 Figure 119 Effect of traditional medicinal prescription for 12 weeks on organ and adipose tissue weights in C57BL/6J mice fed high-fat diet in repeated animal feeding
표 Figure 120. Effect of traditional medicinal prescription for 12 weeks on triglyceride and total cholesterol concentrations in C57BL/6J mice fed high-fat diet in repeated animal feeding
표 Figure 121. Effect of traditional medicinal prescription for 12 weeks on fasting blood glucose and glucose tolerance in C57BL/6J mice fed high-fat diet in repeated animal feeding
표 Figure 122. Effects of BITC on 3T3-L1 CM-stimulated migration of RAW264.7 cells.
표 Figure 123. Effects of crosstalk between adipocytes and macrophages on the production of cytokines/chemokines
표 Figure 124. Changes in transcript levels of cytokines/chemokines in 3T3-L1/RAW264.7 co-culture
표 Figure 125. Effects of BITC on MCP-1 production in RAW264.7/3T3-L1 co-cultures
표 Figure 126. Effects of green tea extract (GT) on LPS-induced nitric oxide (NO) production and cell viability in RAW264.7 murine macrophages
표 Figure 127. Effects of green tea-derived catechins (EGC, EGCG, ECG, EC) on LPS-induced nitric oxide (NO) production and cell viability in RAW264.7 murine macrophages
표 Figure 128. Effects of green tea-derived compounds (caffeine, theobromine, theophylline, L-theanine) on LPS-induced nitric oxide (NO) production and cell viability in RAW264.7 murine macrophages
표 Figure 129. Effects of Taeeumjowuitang components on LPS-induced nitric oxide (NO) production and cell viability in RAW264.7 murine macrophages
표 Figure 130. Effect of green tea and green tea-derived catechins on lipid accumulation in 3T3-L1 cells
표 Figure 131. Effect of green tea-derived compounds on lipid accumulation in 3T3-L1 cells
표 Figure 132. Effect of Taeeumjowuitang components on lipid accumulation in 3T3-L1 cells
표 Figure 133. Effects of green tea extract and green tea-derived catechins on ATCM-stimulated migration of RAW264.7 cells
표 Figure 134. Effects of Taeeumjowuitang components on 3T3-L1 CM-stimulated migration of RAW264.7 cells
표 Figure 135. Effects of green tea-derived catechins on MCP-1 mRNA expression in RAW264.7/3T3-L1 co-cultures
표 Figure 136. Effects of Taeeumjowuitang components on MCP-1 mRNA expression in RAW264.7/3T3-L1 co-cultures
표 Figure 137. Effects of Taeeumjowuitang components on MCP-1 production in RAW264.7/3T3-L1 co-cultures
표 Figure 138. Cytotoxicity of sulforaphene
표 Figure 139. Anti-adipogenic effect of sulforaphene in 3T3-L1 preadipocytes
표 Figure 140. Comparison of anti-adipogenic effect of sulforaphene with various anti-adipogenic agents
표 Figure 141. Effect of sulforaphene on adipogenic marker genes in 3T3-L1 preadipocytes
표 Figure 142. Time-dependent effect of sulforaphene on adipogenesis of 3T3-L1 preadipocytes
표 Figure 143. The effect of Sulforphane on cell viability
표 Figure 144. The effect of Sulforphane on MDI-induced adipogenesis
표 Figure 145. The effect of Sulforphane on protein expression of biomarkers during adipogenesis
표 Figure 146. The effect of Sulforphane on the period of time during adipogenesis
표 Figure 147. The effect of Sulforphane on the progress of cell cycle during early stage of adipogenesis
표 Figure 148. The effect of Sulforphane on HFD-induced increase of body weight
표 Figure 149. The effect of Sulforphane on Food effeiciency ratio
표 Figure 150. Effects of genipin and geniposide on cell viability in 3T3-L1 preadipocytes.
표 Figure 151. Effects of genipin and geniposide on adipogenesis in 3T3-L1 preadipocytes
표 Figure 152. Effect of genipin on the expression of adipogenesisrelated proteins
표 Figure 153. Effect of genipin on lipid contents in 3T3-L1 mature adipocytes
표 Figure 154. Effects of ethanol extracts of Platycodon Grandiflorum Root on weekly changes of body weight in C57BL/6J mice fed high-fat diet for 12 weeks
표 Figure 155. Effects of ethanol extracts of Platycodon Grandiflorum Root supplement for 12weeks on liver, kidney and muscle weight in C57BL/6J mice fed high-fat diet
표 Figure 156. Effects of ethanol extracts of Platycodon Grandiflorum Root supplement for 12weeks on adipose tissue weight in C57BL/6J mice fed high-fat diet
표 Figure 157. Effects of ethanol extracts of Platycodon Grandiflorum Root supplement for 12weeks on fasting blood glucose in C57BL/6J mice fed high-fat diet
표 Figure 158. Effects of ethanol extracts of Platycodon Grandiflorum Root supplement for 12weeks on intraperioneal blood glucose tolerance test in C57BL/6J mice fed high-fat diet
표 Figure 159. Change of plasma triglyceride concentrations for 12 weeks in C57BL/6J mice fed high-fat diet with ethanol extracts of Platycodon Grandiflorum Root
표 Figure 160. Change of plasma total-cholesterol concentrations for 12 weeks in C57BL/6J mice fed high-fat diet with ethanol extracts of Platycodon Grandiflorum Root
표 Figure 161. Effect of Platycodon Grandiflorum Root prescription for 12weeks on plasma lipid profile in C57BL/6J mice fed high-fat diet
표 Figure 162. Effect of ethanol extracts of Platycodon Grandiflorum Root for 12 weeks on energy expenditure in C57BL/6J mice fed high-fat diet in repeated animal feeding
표 Figure 163. Effect of the RSLE, SFE and TAE on body weights of C57BL/6J mice fed with a high-fat diet
표 Figure 164. Effect of the RSLE, SFE and TAE on body composition of C57BL/6J mice fed with a high-fat diet
표 Figure 166. Effect of the RSLE, SFE and TAE on glucose tolerance in C57BL/6J mice fed with a high-fat diet
표 Figure 165. Effect of the RSLE, SFE and TAE on insulin tolerance in C57BL/6J mice fed with a high-fat diet
표 Figure 167. Effect of the RSLE, SFE and TAE on organ weights in C57BL/6J mice fed with a high-fat diet
표 Figure 168. Effect of the RSLE, SFE and TAE on fat weights in C57BL/6J mice fed with high-fat diet
표 Figure 169. Effect of RSLE, SFE, TAE on creatinine levels and ALT activities in the plasma of mice
표 Figure 170. Effect of the RSLE, SFE and TAE on the size of adipocytes in C57BL/6J mice fed with a high-fat diet
표 Figure 170. Effect of the RSLE, SFE and TAE on the size of adipocytes in C57BL/6J mice fed with a high-fat diet
표 Figure 171. Effect of the RSLE, SFE and TAE on lipid acummulation in the liver from C57BL/6J mice fed with a high-fat diet
표 Figure 172. Effect of the RSLE, SFE and TAE on Fecal weight and lipids in C57BL/6J mice fed with a high-fat diet
표 Figure 173. Effect of the RSLE, SFE and TAE on plasma total, LDL HDL cholesterol and triglyceride in C57BL/6J mice fed with a high-fat diet
표 Figure 174. Effect of the RSLE, SFE and TAE on plasma glucose and insulin in C57BL/6J mice fed with a high-fat diet
표 Figure 175. Effect of the RSLE, SFE and TAE on the macrophage infiltration in C57BL/6J mice fed with a high-fat diet
표 Figure 176. Rarefaction Curve
표 Figure 177. Gut microbiota composition (phylum level)
표 Figure 178. Dendrogram of microbiota in each group of mice
표 Figure 179. PCO plot of microbiota in each group of mice
표 Figure 180. Chroma togram of sea buckthorn leaf(A) and sea buckthorn berry(B) extract, ethanol RT, retention time
표 Figure 181. Effects of ethanol extracts of sea buckthorn leaf and sea buckthorn berry on weekly changes of body weight in C57BL/6J mice fed high-fat diet for 12 weeks
표 Figure 182. Effects of ethanol extracts of sea buckthorn leaf and sea buckthorn berry supplement for 12weeks on liver, kidney and muscle weight in C57BL/6J mice fed high-fat diet
표 Figure 183. Effects of ethanol extracts of sea buckthorn leaf and sea buckthorn berry supplement for 12weeks on adipose tissue weight in C57BL/6J mice fed high-fat diet
표 Figure 184. Effects of ethanol extracts of sea buckthorn leaf and sea buckthorn berry supplement for 12weeks on fasting blood glucose in C57BL/6J mice fed high-fat diet
표 Figure 185. Effects of ethanol extracts of sea buckthorn leaf and sea buckthorn berry supplement for 12weeks on intraperioneal blood glucose tolerance test in C57BL/6J mice fed high-fat diet
표 Figure 186. Change of plasma triglyceride concentrations for 12 weeks in C57BL/6J mice fed high-fat diet with ethanol extracts of sea buckthorn leaf and sea buckthorn berry
표 Figure 187. Change of plasma total-cholesterol concentrations for 12 weeks in C57BL/6J mice fed high-fat diet with ethanol extracts of sea buckthorn leaf and sea buckthorn berry
표 Figure 188. Effect of thanol extracts of sea buckthorn leaf and sea buckthorn berry prescription for 12weeks on plasma lipid profile in C57BL/6J mice fed high-fat diet
표 Figure 189. Effect of ethanol extracts of sea buckthorn leaf and sea buckthorn berry for 12 weeks on energy expenditure in C57BL/6J mice fed high-fat diet in repeated animal feeding
표 Figure 190. Previously developed method for sulforaphene detection by HPLC
표 Figure 191. Chromatogram of sulforaphene at 230 nm (top) and 215 nm (bottom)
표 Figure 192. Chromatogram of sulforaphene at 215 nm
표 Figure 193. Chromatogram of sulforaphene by modified mobile phase condition
표 Figure 194. Modified method for sulforaphene detection by HPLC
표 Figure 195. Chromatograms of various concentrations of reference sulforaphene (Sulforaphene concentrations : 50, 125, 250, 500, 1,000 ppm)
표 Figure 196. Calibration curve of reference sulforaphene
표 Figure 197. Sulforaphene concentrations in various extract of Raphani semen
표 Figure 198. Sulforaphene concentrations in various extract of Raphani semen N.D. : not determined
표 Figure 199. Effect of ascorbic acid on sulforaphene concentrations in Raphani semen extract
표 Figure 200. Pilot production of Raphani semen extract

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