PMID- 25945786
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20220408
IS  - 1520-5118 (Electronic)
IS  - 0021-8561 (Linking)
VI  - 63
IP  - 20
DP  - 2015 May 27
TI  - Fisetin Suppresses Lipid Accumulation in Mouse Adipocytic 3T3-L1 Cells by 
      Repressing GLUT4-Mediated Glucose Uptake through Inhibition of mTOR-C/EBPalpha 
      Signaling.
PG  - 4979-87
LID - 10.1021/acs.jafc.5b00821 [doi]
AB  - 3,7,3',4'-Tetrahydroxyflavone (fisetin) is a flavonoid found in vegetables and 
      fruits having broad biological activities. Here the effects of fisetin on 
      adipogenesis and its regulatory mechanism in mouse adipocytic 3T3-L1 cells are 
      studied. Fisetin inhibited the accumulation of intracellular lipids and lowered 
      the expression of adipogenic genes such as peroxisome proliferator-activated 
      receptor gamma and CCAAT/enhancer-binding protein (C/EBP) alpha and fatty acid-binding 
      protein 4 (aP2) during adipogenesis. Moreover, the mRNA levels of genes such as 
      acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase involved 
      in the fatty acid biosynthesis (lipogenesis) were reduced by the treatment with 
      fisetin. The expression level of the glucose transporter 4 (GLUT4) gene was also 
      decreased by fisetin, resulting in down-regulation of glucose uptake. 
      Furthermore, fisetin inhibited the phosphorylation of the mammalian target of 
      rapamycin (mTOR) and that of p70 ribosomal S6 kinase, a target of the mTOR 
      complex, the inhibition of which was followed by a decreased mRNA level of the 
      C/EBPalpha gene. The results obtained from a chromatin immunoprecipitation assay 
      demonstrated that the ability of C/EBPalpha to bind to the GLUT4 gene promoter was 
      reduced by the treatment with fisetin, which agreed well with those obtained when 
      3T3-L1 cells were allowed to differentiate into adipocytes in medium in the 
      presence of rapamycin, an inhibitor for mTOR. These results indicate that fisetin 
      suppressed the accumulation of intracellular lipids by inhibiting GLUT4-mediated 
      glucose uptake through inhibition of the mTOR-C/EBPalpha signaling in 3T3-L1 cells.
FAU - Watanabe, Marina
AU  - Watanabe M
AD  - Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical 
      Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
FAU - Hisatake, Mitsuhiro
AU  - Hisatake M
AD  - Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical 
      Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
FAU - Fujimori, Ko
AU  - Fujimori K
AD  - Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical 
      Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150518
PL  - United States
TA  - J Agric Food Chem
JT  - Journal of agricultural and food chemistry
JID - 0374755
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (CEBPA protein, mouse)
RN  - 0 (Flavonoids)
RN  - 0 (Flavonols)
RN  - 0 (Glucose Transporter Type 4)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - OO2ABO9578 (fisetin)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/cytology/drug effects/*metabolism
MH  - Adipogenesis/drug effects
MH  - Animals
MH  - Biological Transport/drug effects
MH  - CCAAT-Enhancer-Binding Proteins/genetics/*metabolism
MH  - Flavonoids/*pharmacology
MH  - Flavonols
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 4/genetics/*metabolism
MH  - Lipid Metabolism/*drug effects
MH  - Mice
MH  - Promoter Regions, Genetic/drug effects
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
OTO - NOTNLM
OT  - C/EBPalpha
OT  - adipocytes
OT  - fisetin
OT  - glucose uptake
OT  - mTOR
EDAT- 2015/05/07 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/05/07 06:00
PHST- 2015/05/07 06:00 [entrez]
PHST- 2015/05/07 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - 10.1021/acs.jafc.5b00821 [doi]
PST - ppublish
SO  - J Agric Food Chem. 2015 May 27;63(20):4979-87. doi: 10.1021/acs.jafc.5b00821. 
      Epub 2015 May 18.