4-Hydroxyderricin and xanthoangelol from Ashitaba (Angelica keiskei) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways
Version of Record online: 16 MAY 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 10, pages 1729–1740, October 2013
How to Cite
Zhang, T., Sawada, K., Yamamoto, N. and Ashida, H. (2013), 4-Hydroxyderricin and xanthoangelol from Ashitaba (Angelica keiskei) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways. Mol. Nutr. Food Res., 57: 1729–1740. doi: 10.1002/mnfr.201300020
- Issue online: 1 OCT 2013
- Version of Record online: 16 MAY 2013
- Manuscript Accepted: 12 MAR 2013
- Manuscript Revised: 8 MAR 2013
- Manuscript Received: 8 JAN 2013
- AMP-activated protein kinase;
- Ashitaba chalcones;
- CCAAT/enhancer-binding proteins;
- Mitogen-activated protein kinases;
- Peroxisome proliferator-activated receptor gamma
Adipocytes differentiation is deeply involved in the onset of obesity. 4-Hydroxyderricin (4HD) and xanthoangelol (XAG) are the chalcones that are derived from Ashitaba (Angelica keiskei). In this study, we demonstrated the inhibitory effects of these chalcones on adipocytes differentiation.
Methods and results
4HD and XAG suppressed intracellular lipid accumulation by Oil 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 Western 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 CoA carboxylase during differentiation of 3T3-L1 adipocytes accompanied by a decrease in glycerol-3-phosphate acyl transferase-1 and an increase in carnitine palmitoyltransferase-1 mRNA 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 Jun aminoterminal kinases inhibitor abolished the down-expression of C/EBP-α and PPAR-γ, but not C/EBP-β.
4HD and XAG inhibit adipocytes differentiation through AMPK and mitogen-activated protein kinase pathways, resulting in the down-expression of adipocyte-specific transcription factors.