Propionate Inhibits Hepatocyte Lipid Synthesis

Oat bran lowers serum cholesterol in animals and humans. Propionate, a short-chain fatty acid produced by colonic bacterial fermentation of soluble fiber, is a potential mediator of this action. We tested the effect of propionate on hepatocyte lipid synthesis in rats using [1-¹⁴C]acetate, ³H₂O, and [2-¹⁴C]mevalonate as precursors. Propionate produced a statistically significant inhibition of cholesterol biosynthesis from [1-¹⁴C]-acetate at a concentration of 1.0 mM and from ³H₂O and [2-¹⁴C]mevolonate at concentrations of 2.5 mM. Propionate also produced a significant inhibition of fatty acid biosynthesis at concentrations of 2.5 mM using [1-¹⁴C]acetate as a precursor. The demonstration of propionate-mediated inhibition of cholesterol and fatty acid biosynthesis at these concentrations suggests that propionate may inhibit cholesterol and fatty acid biosynthesis in vivo and may mediate in part the hypolipidemic effects of soluble dietary fiber. Further studies are needed to clarify this action of propionate and to establish the exact mechanisms by which the inhibition occurs.