Premium
Dietary plant sterols regulate genes involved in cholesterol metabolism in mouse liver but not intestine
Author(s) -
Jesch Elliot D,
Lee JiYoung,
Carr Timothy P
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.700.35
Subject(s) - sterol , abca1 , cholesterol 7 alpha hydroxylase , cholesterol , stigmasterol , biology , cyp8b1 , reductase , medicine , endocrinology , sterol regulatory element binding protein , excretion , bile acid , campesterol , biochemistry , hmg coa reductase , transporter , gene , enzyme , genetics
Dietary plant sterols reduce intestinal cholesterol absorption, but their role in the modification of genes involved in cholesterol transport and metabolism is uncertain. Several intestinal genes and transcription factors are candidates for regulation by plant sterols. We tested the hypothesis that dietary plant sterols regulate gene expression of putative sterol transporters in the small intestine. Male C57BL/6 mice were fed modified versions of the AIN‐93M purified rodent diet with either stigmasterol or sitosterol at 3.94 g/kg diet to reflect the 2 g/day recommendation for humans, based on a 2000 kcal diet. Total RNA was extracted from the duodenum and liver of each mouse and NPC1L1, SRBI, SREBP‐2, HMG CoA Reductase, PPARδ, ABCA1, and ABCG5 mRNA was quantified by real time PCR. Fecal neutral sterol and bile acid output, gallbladder bile, plasma and liver lipids were also quantified. While plant sterols had no effect on plasma lipids or gene expression in the intestine, liver lipids and gene expression of SREBP‐2, HMG CoA Reductase, and ABCA1 in the liver of mice fed plant sterols were significantly reduced compared to controls. Furthermore, sitosterol—and, to a lesser extent, stigmasterol—significantly increase fecal neutral sterol excretion. These data indicate that not only do individual plant sterols increase neutral sterol excretion, but they also play a role in regulating the expression of cholesterol homeostasis genes in the liver. [Supported by USDA‐NRI Competitive Grant No. 2007‐35200‐18298]