Short-chain fatty acids suppress cholesterol synthesis in rat liver and intestine

We previously showed that plasma cholesterol levels decreased following ing estion of a short-chain fatty acid (SCFA) mixture composed of sodium salts of acetic, propionic, and butyric acids simulating cecal fermentation produ cts of sugar-beet fiber (SBF). In the present study, we investigated whethe r hepatic and small intestinal cholesterol synthesis is involved in the cho lesterol-lowering effects of SCFA and SBF. In vitro (expt. 1) and in vivo ( expt. 2) cholesterol synthesis rates and the diurnal pattern of SCFA concen trations in portal plasma (expt. 3) were studied in three separate experime nts in rats fed diets containing the SCFA mixture, SBF(100 g/kg diet), or t he fiber-free control diet. Cholesterol synthesis was measured using (H2O)- H-3 as a tracer. The in vitro rate of cholesterol synthesis, measured using liver slices, was greater in the SBF group, but not in the SCFA group, tha n in the fiber-free control group. In contrast, the hepatic cholesterol syn thesis rate in vivo was lower in the SCFA group, but not in the SBF group, than in the control group. The mucosal cholesterol synthesis rate for the w hole small intestine was <50% of the hepatic rate. The rate in the proximal region was slightly but significantly lower in the SCFA group, and was sig nificantly higher in the SBF group than in the fiber-free group. The rate i n the distal small intestines was also significantly greater in the SBF gro up than in the fiber-free group. Plasma total cholesterol concentrations we re lower in the SCFA and SBF groups than in the fiber-free group in both ex periments 2 and 3. Diurnal changes in portal SCFA and cholesterol levels we re studied in the experiment 3. SCFA concentrations increased rapidly after the start of feeding the SCFA diet, and changes in plasma cholesterol were the reciprocal of those observed in SCFA. These results show that a decrea se in hepatic cholesterol synthesis rate mainly contributes to the lowering of plasma cholesterol in rats fed the SCFA mixture diet. Changes in portal SCFA and cholesterol concentrations support this conclusion. In SBF-fed ra ts, SCFA produced by cecal fermentation are possibly involved in lowering p lasma cholesterol levels by negating the counteractive induction of hepatic cholesterol synthesis caused by an increase in bile acid excretion.