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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| Institution: | 1. Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 16419, Korea;2. Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do 55365, Korea;3. College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea;4. Graduate School of East–West Medical Science, Kyung Hee University, Yongin 17104, Korea;1. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy;2. Laboratory of Molecular Biology, Department of Agricultural Biotechnology, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece;3. Istituto di Biochimica delle Proteine — CNR, Via P. Castellino 111, 80131 Napoli, Italy;4. Università degli Studi di Firenze, Polo Scientifico, Dipartimento di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;1. Department III of Internal Medicine, Heart Centre of the University of Cologne, Cologne, Germany;2. Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom;3. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom |
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| 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. |
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