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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Younghyun Lee

농업생명과학대학 농생명공학부
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서울대학교 대학원
학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2016. 8. 이기원.
Cacao (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.
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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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