Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes

Eur J Nutr. 2013 Oct;52(7):1755-69. doi: 10.1007/s00394-012-0479-1. Epub 2012 Dec 21.

Abstract

Purpose: We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol-lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect.

Methods: Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks.

Results: C57BL/6 NCrl mice responded to oat bran with 19 ± 1 % (P < 0.001) lower plasma cholesterol, 40 ± 5% (P < 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indicated improved glycemic control by oat bran in C57BL/6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower numbers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl.

Conclusions: Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol-lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avena / chemistry*
  • Bile Acids and Salts / metabolism*
  • Body Weight
  • Cholesterol / blood
  • Cholesterol 7-alpha-Hydroxylase / genetics
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Cholesterol Esters / metabolism
  • Diet, Atherogenic
  • Dietary Fiber / administration & dosage
  • Feces / chemistry
  • Female
  • Fructosamine / blood
  • Glucose Tolerance Test
  • Intestinal Absorption / physiology
  • Intestines / microbiology
  • Lipid Metabolism
  • Liver / enzymology*
  • Mice
  • Mice, Inbred C57BL
  • Microbiota*
  • Multivariate Analysis
  • Principal Component Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Steroid 12-alpha-Hydroxylase / genetics
  • Steroid 12-alpha-Hydroxylase / metabolism
  • Up-Regulation

Substances

  • Bile Acids and Salts
  • Cholesterol Esters
  • Dietary Fiber
  • RNA, Messenger
  • Fructosamine
  • Cholesterol
  • Cholesterol 7-alpha-Hydroxylase
  • Cyp7a1 protein, mouse
  • Steroid 12-alpha-Hydroxylase