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5-(3, 4-Dihydroxyphenyl)-γ-valerolactone, a Metabolite of Procyanidins in Cacao, Suppresses MDI-induced Adipogenesis by Regulating Cell Cycle Progression

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dc.contributor.advisor이기원-
dc.contributor.authorYounghyun Lee-
dc.date.accessioned2017-07-14T06:47:30Z-
dc.date.available2018-10-25-
dc.date.issued2016-08-
dc.identifier.other000000137075-
dc.identifier.urihttps://hdl.handle.net/10371/125968-
dc.description학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2016. 8. 이기원.-
dc.description.abstractCacao (Theobroma cacao) which includes a large amount of polyphenols, has been reported to have potent beneficial effects on obesity. However, all of these previous studies have focused on the extract form of cacao or procyanidins and their potential mechanisms have not been fully elucidated with considering ADME (absorption, distribution, metabolism, and excretion). Here, in this study, I investigated the inhibitory effects of metabolites of procyanidins on adipogenic cocktail (MDI)-induced adipogenesis and lipogenesis in 3T3-L1 preadipocytes. Especially, 5-(3, 4-Dihydroxyphenyl)-γ-valerolactone (DHPV) which is known for the major metabolite of proycanidins, had the best inhibitory effects on adipogenesis and lipogenesis. I found that DHPV decreased the protein expression levels which are involved in adipogenesis such as peroxisome proliferator-activated receptor γ (PPAR γ) and CCAT/enhancer-binding protein α (C/EBP α), and lipogenesis such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) dose-dependently. These inhibitory effects were mainly due to G1 phase arrest in the early stage of adipogenesis which called as mitotic clonal expansion (MCE) by suppressing cell proliferation. In kinase array, CDK2/cyclin O was preferentially selected through several citeria. DHPV directly suppressed activation of CDK2/cyclin O complex. DHPV inhibited the phosphorylation of C/EBP β which is responsible for induction of PPAR γ and C/EBP α. Taken together, this study implied that DHPV is one of the biologically active compound of cacao which brings the potential benefits on anti-obesity by inhibiting intracellular lipid contents and cell differentiation.-
dc.description.tableofcontentsⅠ. INTRODUCTION 1

Ⅱ. MATERIALS AND METHODS 5
1. Chemicals and reagents 5
2. Cell culture and preadipocytes differentiation 6
3. Cell viability assay 7
4. Oil Red O staining 8
5. Glycerol assay 9
6. Western blot 10
7. Flow cytometry using a FACS 11
8. Kinase assay 12
9. Pull-down assay 13
10. Statistical analysis 14

Ⅲ. RESULTS 15
1. DHPV had the most potent inhibitory effects on MDI-induced adipogenesis in 3T3-L1 preadipocytes 15
2. DHPV inhibited the adipogenic and lipogenic effects in 3T3-L1 preadipocytes 21
3. DHPV inhibited MDI-induced adipogenesis at mitotic clonal expansion step in 3T3-L1 preadipocytes 25
4. DHPV blocked the cell cycle progression by inducing G1 arrest in 3T3-L1 preadipocytes 29
5. DHPV directly inhibited CDK2/cyclin O activity 33
6. DHPV decreased lipid accumulation in 3T3-L1 mature adipocytes 45

Ⅳ. DISCUSSION 50

Ⅴ. REFERENCES 57

Ⅵ. 국문 초록 66
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dc.formatapplication/pdf-
dc.format.extent1344374 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subject5-(3’-
dc.subject4’-Dihydroxyphenyl)-γ-valerolactone-
dc.subject.ddc630-
dc.title5-(3, 4-Dihydroxyphenyl)-γ-valerolactone, a Metabolite of Procyanidins in Cacao, Suppresses MDI-induced Adipogenesis by Regulating Cell Cycle Progression-
dc.typeThesis-
dc.description.degreeMaster-
dc.citation.pages67-
dc.contributor.affiliation농업생명과학대학 농생명공학부-
dc.date.awarded2016-08-
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College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Agricultural Biotechnology (농생명공학부)Theses (Master's Degree_농생명공학부)
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