Isoflavones as a smart curer for non-alcoholic fatty liver disease and pathological adiposity via ChREBP and Wnt signaling.
OBJECTIVE
Non-alcoholic fatty liver disease (NAFLD) and pathological adiposity has emerged as an important modern disease. Along with this, the requirement for alternative and natural medicine for preventing NAFLD and adiposity has been increasing rapidly and considerably. In this report, we will review the biological effect and mechanisms of soy isoflavones on NAFLD and pathologic adiposity mainly through the novel pathways, de novo lipogenic carbohydrate responsive element binding protein (ChREBP) and anti-adipogenic Wnt signaling.


METHODS
This paper reviews in vitro and in vivo isoflavone studies published in 2002 to 2011 in North America and East Asia.


RESULTS
Collectively, the data support a beneficial relation of isoflavones and NAFLD and/or adiposity. Isoflavones suppress ChREBP signaling via protein kinase A (PKA) and/or 5'-AMP activated protein kinase (AMPK)-dependent phosphorylation, which prevents ChREBP from binding to the promoter regions of lipogenic enzyme. Furthermore, isoflavones directly stimulate Wnt signaling via estrogen receptors-dependent pathway, which inactivates glycogen synthase kinase-3 beta (GSK-3β), transactivate T-cell factor/lymphoid-enhancer factor (TCF/LEF), the effector of Wnt signaling, degrade adipogenic peroxisome proliferator-activated receptor γ (PPARγ), augment p300/CBP, the transcriptional co-activators of TCF/LEF.


CONCLUSIONS
Natural compound isoflavones may be useful alternative medicines in preventing NAFLD and pathological adiposity and this action may be partially associated with ChREBP and Wnt signaling.
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, 599 Gwanakno, Sillim-dong, Gwanak-gu, Seoul 151-742, Republic of Korea.
Mi-Hyun
MH
Kim
Kyung-Sun
KS
Kang
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005234:Fatty Liver / Q000188:drug therapy* / Q000517:prevention & control; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013025:Glycine max; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism; D051153:Wnt Proteins / Q000187:drug effects* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D007529:Isoflavones; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D051153:Wnt Proteins