The chalcones cardamonin and flavokawain B inhibit the differentiation of preadipocytes to adipocytes by activating ERK.
OBJECTIVE
We searched for polyphenols capable of inhibiting the lipid accumulation in 3T3-L1 cells, and investigated the mechanisms of two effective chalcones cardamonin and flavokawain B on differentiation of preadipocytes.


RESULTS
We treated 3T3-L1 cells with a panel of 46 polyphenols and measured intracellular lipid accumulation by Sudan II staining. Four of them, including cardamonin and flavokawain B, inhibited lipid accumulation. In the further study, cardamonin and flavokawain B inhibited lipid accumulation by downregulating the expression of CCAAT/enhancer binding protein (C/EBP)-β, C/EBPα, and peroxisome proliferator-activated receptor-γ (PPARγ) at both mRNA and protein levels. Cardamonin and flavokawain B also increased phosphorylation of extracellular signal-regulated kinase (ERK) in the early phase of adipocyte differentiation. PD98059, an ERK inhibitor, restored C/EBPβ, PPARγ expression and intracellular lipid accumulation in adipocytes. Moreover, cardamonin and flavokawain B also modulated the secretion of C-reactive protein, dipeptidyl peptidase IV, interleukin-6, tumor necrosis factor-α and fibroblast growth factor-21 in mature adipocytes.


CONCLUSIONS
These results indicate that ERK activation and consequent downregulation of adipocyte-specific transcription factors are involved in the inhibitory effects of the chalcones cardamonin and flavokawain B on adipocyte differentiation. Moreover, cardamonin and flavokawain B are able to modulate secretion of adipokines in mature adipocytes.
Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.
Tianshun
T
Zhang
Food Science Research Center, House Wellness Foods Corporation, Imoji 3-20, Itami, Hyogo 664-0011, Japan.
Norio
N
Yamamoto
Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.
Yoko
Y
Yamashita
Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan. Electronic address: ashida@kobe-u.ac.jp.
Hitoshi
H
Ashida
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D047188:Chalcones / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D054392:Adipokines; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C545013:Cebpb protein, mouse; D047188:Chalcones; D005419:Flavonoids; D051275:Glucose Transporter Type 4; D047495:PPAR gamma; D059808:Polyphenols; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; C452039:flavokawain B; D048049:Extracellular Signal-Regulated MAP Kinases; C436747:cardamonin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
CCAAT/enhancer-binding proteins; Cardamonin; Extracellular signal-regulated kinase; Flavokawain B; Peroxisome proliferator-activated receptor-γ