4'-Hydroxyflavanone suppresses activation of sterol regulatory element-binding proteins and de novo lipid synthesis.
Sterol regulatory element-binding proteins (SREBPs) are major transcription factors that regulate the expression of genes involved in fatty acid and cholesterol biosynthesis. Here we show that 4'-hydroxyflavanone (4'-HF) impairs the fatty acid synthase promoter activity and reduces the activation of SREBPs and their target gene expression in human hepatoma Huh-7 cells. Moreover, 4'-HF suppresses de novo fatty acid and cholesterol synthesis. This study identifies 4'-HF as an inhibitor of SREBP maturation and lipid synthesis, and provides evidence that 4'-HF may have major potential as a pharmaceutical preparation against hepatic steatosis and dyslipidemia.
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
Shingo
S
Miyata
Jun
J
Inoue
Makoto
M
Shimizu
Ryuichiro
R
Sato
D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D050155:Lipogenesis; D011401:Promoter Regions, Genetic; D051779:Sterol Regulatory Element Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D044950:Flavanones; D051779:Sterol Regulatory Element Binding Proteins; C561123:4'-hydroxyflavanone; D002784:Cholesterol; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I