title: Antiadipogenic and proosteogenic effects of luteolin, a major dietary flavone, are mediated by the induction of DnaJ (Hsp40) Homolog, Subfamily B, Member 1.
abstract: Luteolin (3,4,5,7-tetrahydroxyflavones), a major dietary flavone, regulates a variety of biological effects including cancer progression, insulin resistance and inflammation. However, its exact actions on adipogenesis and osteogenesis and the underlying molecular mechanisms are yet to be clarified. In this study, we show that luteolin suppresses lipid accumulation but increases osteoblast differentiation. In mechanism studies, luteolin increases the expression of the heat shock proteins (Hsp) 40 (Dnajb1) and Hsp90 (Hsp90b1), but not those of other heat shock proteins including Hsp20, Hsp27, Hsp47, Hsp70, Hsp72, and Hsp90, and another type of Hsp40 (Dnaja1). Silencing Dnajb1 by using small interfering RNAs (siRNAs), but not against Hsp90b1, recapitulates the effects of luteolin in adipocyte and osteoblast differentiation. Consistently, the forced expression of Dnajb1 decreases the lipid accumulation and stimulates alkaline phosphatase (ALPL) activity. The antiadipogenic and proosteogenic effects of luteolin are significantly blunted in Dnajb1-deficient cells, further suggesting that Dnajb1 is, at least in part, required for luteolin's dual actions in adipogenesis and osteogenesis. Together, our data implicate luteolin as an ingredient and Dnajb1 as a molecular target for the development of functional foods and drugs in metabolic and bone-related diseases.
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: So-Mi
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Suji
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: No-Joon
authors.initials: NJ
authors.lastname: Song
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Seo-Hyuk
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do 55365, Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Hwang
authors.affiliation: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
authors.forename: Dong Kwon
authors.initials: DK
authors.lastname: Yang
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Joung-Woo
authors.initials: JW
authors.lastname: Hong
authors.affiliation: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
authors.affiliation: Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Korea. Electronic address: kwpark@skku.edu.
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*
chemical_list: D050956:HSP40 Heat-Shock Proteins; D047311:Luteolin
keywords: Adipocyte differentiation; Dnajb1; Heat shock protein; Luteolin; Osteoblast differentiation