Antiadipogenic and proosteogenic effects of luteolin, a major dietary flavone, are mediated by the induction of DnaJ (Hsp40) Homolog, Subfamily B, Member 1

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• 作者：So-Mi Kwon^a ; Suji Kim^a ; No-Joon Song^a ; Seo-Hyuk Chang^a ; Yu-Jin Hwang^b ; Dong Kwon Yang^c ; Joung-Woo Hong^d ; Woo Jin Park^c ; Kye Won Park^a ; ^{kwpark@skku.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Pparγ ; peroxisome proliferator activated receptor γ ; aP2 ; adipocyte protein 2 ; siRNA ; small interfering RNA ; MSC ; mesenchymal stem cells ; DMI ; Dexamethasone ; IBMX ; and Insulin ; Dnajb1 ; DnaJ (Hsp40) Homolog ; Subfamily B ; Member 1 ; LCA ; licochalcone A ; TNF-α ; Tumor necrosis factor α ; JNK ; c-Jun N-terminal Kinase ; IGF-1 ; Insulin like growth factor-1 ; Wnt ; Wingless-INT ; mTOR ; mammalian target of rapamycin ; AMPK ; AMP- activated protein kinase ; MSC ; Mesenchymal stem cells ; TGF-β1 ; transforming growth
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：30
• 期：Complete
• 页码：24-32
• 全文大小：928 K

文摘

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.