Effect of Hormones and Short Chain Fatty Acids on CYP7A1 Gene Expression in HepG2 Cell

호르몬과 단쇄지방산이 HepG2 Cell 내에서 CYP7A1 발현에 미치는 효과

  • Yang, Jeong-Lye (Research Institute Of Human Ecology, Changwon University) ;
  • Lee, Hyun-Jung (Dept. of Food and Nutritional Sciences, Ewha Womans University) ;
  • Kim, Yang-Ha (Dept. of Food and Nutritional Sciences, Ewha Womans University)
  • 양정례 (창원대학교 생활과학연구소) ;
  • 이현정 (이화여자대학교 식품영양학과) ;
  • 김양하 (이화여자대학교 식품영양학과)
  • Published : 2005.06.01


Cholesterol $7\alpha-hydroxylase$ (CYP7A1) is the rate-limiting enzyme in the conversion of cholesterol to bile acids and plays a central role in regulating cholesterol homeostasis. We previously showed that a fermentable $\beta-glucan$ ingestion decreased plasma cholesterol levels due to fecal bile acid excretion elevation involved inincrease of cholesterol $7\alpha-hydroxylase$ mRNA expression and activity. It is proposed that short chain fatty acids (SCFA) produced by cecal and colonic fermentation of soluble fiber are associated with cholesterol-lowering effect of fiber. In the present study, we investigated whether CYP7A1 expression is up-regulated by short chain fatty acids or by hormones in cultured human hepatoma (HepG2) cells. Confluent HepG2 cell were incubated with acetate, propionate, or butyrate at 1 mM concentration for 24 hrs. Acetate as well as propionate increased to 1.8-fold expression of CYP7A1 mRNA than the control. Butyrate also increased 1.5-fold expression of CYP7A1 mRNA. Our data show for the first time that SCFA increase expression of CYP7A1 mRNA. Adding insulin, dexamethasone and triiodothyronine $(1\;{\mu}M)$ to HepG2 cell increased the expression of CYP7A1 mRNA to $150\%,\;173\%,\;141\%$, respectively. These results suggest that SCFA produced by cecal fermentation stimulate enteric nervous system, in which secreted some neuropeptides may be responsible for change in cholesterol and bile acid metabolism. These findings suggest that SCFA are involved in lowering plasma cholesterol levels due to the up-regulation of CYP7A1 and bile acid synthesis.


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