TY - JOUR
T1 - Hypocholesterolemic effect of daily fisetin supplementation in high fat fed Sprague-Dawley rats
AU - Shin, Min Jeong
AU - Cho, Yoonsu
AU - Moon, Jiyoung
AU - Jeon, Hyun Ju
AU - Lee, Seung Min
AU - Chung, Ji Hyung
N1 - Funding Information:
This research was supported by Basic Science Research Program through the National research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012-0002119).
PY - 2013/7
Y1 - 2013/7
N2 - We aimed to test whether fisetin could modulate cholesterol homeostasis in rats with diet-induced hypercholesterolemia, and further investigated the underlying mechanisms by which fisetin exerts its cholesterol lowering effect. Blood lipid profile, hepatic cholesterol content, as well as gene expressions in cholesterol metabolism were examined. Elevated levels of total cholesterol and LDL-cholesterol, along with hepatic cholesterol content in a high fat group were found to be significantly reduced by fisetin. The high fat diet significantly decreased hepatic mRNA levels of LDLR, SREBP2, HMGCR and PCSK9 in comparison to the control diet, however, fisetin did not further elicit any changes in mRNA levels of the same genes. The high fat diet dramatically increased the transcript levels of CYP7A1, which was subsequently reversed by the fisetin. In HepG2 cells, fisetin was found to increase the levels of a nuclear form of SREBP2 and LDLR. In conclusion, fisetin supplementation displayed hypocholesterolemic effects by modulating the expression of genes associated with cholesterol and bile acid metabolism.
AB - We aimed to test whether fisetin could modulate cholesterol homeostasis in rats with diet-induced hypercholesterolemia, and further investigated the underlying mechanisms by which fisetin exerts its cholesterol lowering effect. Blood lipid profile, hepatic cholesterol content, as well as gene expressions in cholesterol metabolism were examined. Elevated levels of total cholesterol and LDL-cholesterol, along with hepatic cholesterol content in a high fat group were found to be significantly reduced by fisetin. The high fat diet significantly decreased hepatic mRNA levels of LDLR, SREBP2, HMGCR and PCSK9 in comparison to the control diet, however, fisetin did not further elicit any changes in mRNA levels of the same genes. The high fat diet dramatically increased the transcript levels of CYP7A1, which was subsequently reversed by the fisetin. In HepG2 cells, fisetin was found to increase the levels of a nuclear form of SREBP2 and LDLR. In conclusion, fisetin supplementation displayed hypocholesterolemic effects by modulating the expression of genes associated with cholesterol and bile acid metabolism.
KW - CYP7A1
KW - Cholesterol
KW - Fisetin
KW - HMG-CoA reductase
KW - Hypercholesterolemia
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U2 - 10.1016/j.fct.2013.03.010
DO - 10.1016/j.fct.2013.03.010
M3 - Article
C2 - 23524313
AN - SCOPUS:84876310011
VL - 57
SP - 84
EP - 90
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
SN - 0278-6915
ER -