title: Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes.
abstract: Toddalia asiatica (L.) Lam. (T. asiatica) has been utilized traditionally for medicinal purposes such as the treatment of diabetes. Currently, the extract is considered to be a good source of anti-diabetic agents, but the active compounds have yet to be identified. In this study, we investigated the effects of fractionated T. asiatica extracts on the differentiation of 3T3-L1 preadipocytes and identified aculeatin as a potential active agent. When 3T3-L1 preadipocytes were treated with aculeatin isolated from T. asiatica in the presence of insulin, aculeatin increased cellular triglyceride levels and glycerol-3-phosphate dehydrogenase activity. This indicated that aculeatin could enhance the differentiation of preadipocytes into adipocytes. Further analyses using a DNA microarray and real-time quantitative reverse-transcription PCR showed an increase in the expression of peroxisome proliferator-activated receptor-γ target genes (Pparg, Ap2, Cd36, Glut4 and Adipoq) by aculeatin, suggesting that aculeatin enhances the differentiation of 3T3-L1 cells by modulating the expression of genes critical for adipogenesis. Interestingly, after treatment of differentiated adipocytes with aculeatin, glucose uptake and lipolysis were enhanced. Overall, our results suggested that aculeatin is an active compound in T. asiatica for enhancing both differentiation and lipolysis of adipocytes, which are useful for the treatment of lipid abnormalities as well as diabetes.
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan; Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555, Japan. Electronic address: watanabea@jfrl.or.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yoshida
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Harada
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mishima
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Japan Food Research Laboratories, Osaka 567-0085, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Watai
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D041721:3T3-L1 Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003374:Coumarins / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D027821:Rutaceae / Q000737:chemistry*
chemical_list: D003374:Coumarins; D003512:Cyclohexanones; D010936:Plant Extracts
keywords: 3T3-L1 cells; Aculeatin; Adipogenesis; Toddalia asiatica (L.) Lam.