PMID- 23627466
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20220408
IS  - 1744-5116 (Electronic)
IS  - 1388-0209 (Linking)
VI  - 51
IP  - 7
DP  - 2013 Jul
TI  - Genistein sensitizes hepatic insulin signaling and modulates lipid regulatory 
      genes through p70 ribosomal S6 kinase-1 inhibition in high-fat-high-fructose 
      diet-fed mice.
PG  - 815-24
LID - 10.3109/13880209.2013.766896 [doi]
AB  - CONTEXT: Genistein reduces high-calorie diet-induced insulin resistance and fat 
      accumulation in animals, but the mechanism is unresolved. OBJECTIVE: This study 
      explores whether action of genistein is associated with p70 ribosomal S6 kinase-1 
      (S6K1) inhibition. MATERIALS AND METHODS: Adult male mice were fed either normal 
      diet or high-fat-high-fructose diet (HFFD) for 15 days, after which animals in 
      each dietary group were divided into two groups and administered either genistein 
      (1 mg kg(-1) day(-1), p.o.) in 0.5 ml of 30% dimethylsulfoxide (DMSO) or 30% DMSO 
      (0.5 ml) for the next 45 days. At the end of the study, their liver was analyzed 
      for lipid content. Semi-quantitative RT-PCR and western blotting methods were 
      used to analyze lipid regulatory genes and insulin signaling proteins, 
      respectively. RESULTS: Genistein significantly (p < 0.05) lowered HFFD-induced 
      body and liver weight gain and plasma and hepatic lipid levels. Histology showed 
      a 2.5-fold increase of lipid in HFFD compared to control. Genistein treatment to 
      HFFD-fed animals significantly decreased lipid accumulation (by 40%) compared to 
      HFFD. Insulin-stimulated tyrosine phosphorylation of insulin receptor-beta and 
      insulin receptor substrates-1 (IRS-1), IRS-1 associated 
      phospatidylinositol-3kinase (PI3K) and Akt Ser(473) phosphorylation were improved 
      while IRS-1 serine phosphorylation was significantly (p < 0.05) decreased by 
      genistein in HFFD. Significant (p < 0.05) increase in adenosine 
      monophosphate-activated protein kinase (AMPK) Thr(172) phosphorylation and 
      decrease in S6K1 Thr(389) phosphorylation were observed in HFFD-plus genistein 
      compared to HFFD. Genistein downregulated lipogenic genes and upregulated fatty 
      acid oxidative genes in HFFD-fed mice. CONCLUSION: Genistein improves insulin 
      signaling and attenuates fat accumulation in liver through S6K1 inhibition.
FAU - Arunkumar, Elumalai
AU  - Arunkumar E
AD  - Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, 
      India.
FAU - Karthik, Dhanapalan
AU  - Karthik D
FAU - Anuradha, Carani Venkatraman
AU  - Anuradha CV
LA  - eng
PT  - Journal Article
DEP - 20130429
PL  - England
TA  - Pharm Biol
JT  - Pharmaceutical biology
JID - 9812552
RN  - 0 (Fatty Acids)
RN  - 0 (Insulin)
RN  - 30237-26-4 (Fructose)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (Rps6ka1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Diet, High-Fat
MH  - Down-Regulation/drug effects
MH  - Fatty Acids/metabolism
MH  - Fructose/administration & dosage
MH  - Genistein/*pharmacology
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Lipid Metabolism/drug effects
MH  - Lipogenesis/genetics
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Phosphorylation/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Protein S6 Kinases, 90-kDa/*antagonists & inhibitors
MH  - Up-Regulation/drug effects
EDAT- 2013/05/01 06:00
MHDA- 2014/02/14 06:00
CRDT- 2013/05/01 06:00
PHST- 2013/05/01 06:00 [entrez]
PHST- 2013/05/01 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
AID - 10.3109/13880209.2013.766896 [doi]
PST - ppublish
SO  - Pharm Biol. 2013 Jul;51(7):815-24. doi: 10.3109/13880209.2013.766896. Epub 2013 
      Apr 29.