title: Shikonin inhibits adipogenic differentiation via regulation of mir-34a-FKBP1B.
abstract: Shikonin is a naturally occurring naphthoquinone pigment and a major constituent present in Lithospermum erythrorhizon. Since microRNAs (miRNAs) are one of the key post-transcriptional regulators of adipogenesis, their manipulation represents a potential new strategy to inhibit adipogenesis. Our aim was to investigate shikonin-dependent inhibition of adipogenesis with an emphasis on miRNA-related processes. Mir-34a increased during induced adipogenesis, and this was suppressed in the presence of shikonin. mRNA expression of FKBP1B, a suggested target of mir-34a according to bioinformatics studies, decreased during adipogenesis, but was recovered by shikonin treatment, which reversely correlated with mir-34a expression. A mir-34a inhibitor suppressed MDI-induced adipogenesis by blocking PPARγ and C/EBPα expression, while suppression of mir-34a recovered MDI-induced down-regulation of FKBP1B expression. A mir-34a mimic decreased FKBP1B mRNA expression in 3T3-L1 preadipocytes. We also observed that mir-34a bound directly to the 3'-untranslated region of FKBP1B. Finally, FKBP1B overexpression attenuated MDI-induced adipogenesis, PPARγ, and C/EBPα expression. These results suggest that mir-34a regulates adipogenesis by targeting FKBP1B expression. Our findings reveal that shikonin prevents adipogenesis by blocking the mir-34a-FKBP1B pathway which represents a promising potential target for preventing obesity.
authors.affiliation: Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam, Republic of Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam, Republic of Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Gwon
authors.affiliation: Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam, Republic of Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, Republic of Korea. Electronic address: tyhap@kfri.re.kr.
authors.forename: Tae Youl
authors.initials: TY
authors.lastname: Ha
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D009285:Naphthoquinones / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D009285:Naphthoquinones; D022021:Tacrolimus Binding Proteins; C551848:MIRN34a microRNA, mouse; C016101:shikonin; C509259:FKBP1B protein, mouse
keywords: Adipogenesis; FKBP1B; Mir-34a; Shikonin