Suppression of adipocyte differentiation by Cordyceps militaris through activation of the aryl hydrocarbon receptor.
Mycelial extracts have a wide range of biological activities that modulate functions of mammalian cells. In this report, we sought to identify antiadipogenic mycelia with the use of 3T3-L1 cells and found that the extract of Cordyceps militaris exclusively suppressed differentiation of 3T3-L1 preadipocytes into mature adipocytes without affecting cell viability. This inhibitory effect was dose dependent, reversible, and associated with 1) a decrease in lipid accumulation, 2) blunted induction of adipocyte markers including adiponectin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha, and 3) sustained expression of a preadipocyte marker, monocyte chemoattractant protein-1. C. militaris also significantly decreased accumulation of lipid and hypertrophy in mature adipocytes and preserved their response to insulin (phosphorylation of Akt) during prolonged culture. Subsequent experiments revealed that C. militaris has the potential to activate the aryl hydrocarbon receptor (AhR). In 3T3-L1 cells, treatment with AhR agonists including benzo[a]pyrene and 3-methylcholanthrene reproduced the antiadipogenic effect of C. militaris. Furthermore, dominant-negative inhibition of AhR abrogated the suppressive effect of C. militaris on adipocyte differentiation. These results suggest that C. militaris has the potential to interfere with adipocyte differentiation through activation of AhR.
Shimada
Tsuyoshi
T
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Hiramatsu
Nobuhiko
N
Kasai
Ayumi
A
Mukai
Mai
M
Okamura
Maro
M
Yao
Jian
J
Huang
Tao
T
Tamai
Minori
M
Takahashi
Shuhei
S
Nakamura
Tomoyuki
T
Kitamura
Masanori
M
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds; D015415:Biomarkers; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D032661:Cordyceps / Q000737:chemistry*; D004147:Dioxins / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005562:Formazans; D007202:Indicators and Reagents; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects*
D001391:Azo Compounds; D015415:Biomarkers; D004147:Dioxins; D005562:Formazans; D007202:Indicators and Reagents; D018336:Receptors, Aryl Hydrocarbon; D000469:Alkaline Phosphatase; C011049:oil red O