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4‐Hydroxyderricin and xanthoangelol from A shitaba ( A ngelica keiskei ) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways
Author(s) -
Zhang Tianshun,
Sawada Keisuke,
Yamamoto Norio,
Ashida Hitoshi
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300020
Subject(s) - ampk , kinase , protein kinase a , chemistry , p38 mitogen activated protein kinases , mapk/erk pathway , peroxisome proliferator activated receptor , phosphorylation , microbiology and biotechnology , adipocyte , ccaat enhancer binding proteins , signal transduction , transcription factor , biochemistry , biology , receptor , adipose tissue , nuclear protein , gene
Scope Adipocytes differentiation is deeply involved in the onset of obesity. 4‐Hydroxyderricin (4 HD ) and xanthoangelol ( XAG ) are the chalcones that are derived from A shitaba ( A ngelica keiskei ). In this study, we demonstrated the inhibitory effects of these chalcones on adipocytes differentiation. Methods and results 4 HD and XAG suppressed intracellular lipid accumulation by O il red O staining at 5 μM without cytotoxicity. They inhibited adipocytes differentiation accompanied by down‐expression of adipocyte‐specific transcription factors, CCAAT /enhancer‐binding protein‐β ( C / EBP ‐β), C / EBP ‐α, and peroxisome proliferator‐activated receptor gamma ( PPAR ‐γ) using RT ‐ PCR and W estern blotting analysis. To obtain insights into the underlying mechanism, the activation of AMP ‐activated protein kinase ( AMPK ) and mitogen‐activated protein kinase pathways was investigated. These two chalcones promoted phosphorylation of AMPK and acetyl C o A carboxylase during differentiation of 3 T 3‐ L 1 adipocytes accompanied by a decrease in glycerol‐3‐phosphate acyl transferase‐1 and an increase in carnitine palmitoyltransferase‐1 m RNA expression. These chalcones also promoted phosphorylation of extracellular signal‐regulated kinases and Jun aminoterminal kinases, but not p38. Moreover, the inhibitors for AMPK and extracellular signal‐regulated kinases abolished the chalcones‐caused down‐expression of C / EBP ‐β, C / EBP ‐α, and PPAR ‐γ. Treatment with J un aminoterminal kinases inhibitor abolished the down‐expression of C / EBP ‐α and PPAR ‐γ, but not C / EBP ‐β. Conclusion 4 HD and XAG inhibit adipocytes differentiation through AMPK and mitogen‐activated protein kinase pathways, resulting in the down‐expression of adipocyte‐specific transcription factors.