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]mevalonate 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.

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Abstract-High plasma triglyceride concentrations in diabetic subjects increase their risk for developing coronary heart disease. Numerous studies have shown that the high density lipoprotein (HDL) composition is abnormal in type 2 diabetic subjects. One study has shown that HDL (lipoprotein A-I) isolated from subjects with non-insulin-dependent diabetes mellitus exhibits a decreased capacity to induce cholesterol efflux. The current study examined the effect of HDL 2 and HDL 3 subfractions from poorly controlled type 2 diabetic and control subjects on THP-1 macrophagemediated low density lipoprotein (LDL) oxidation. The composition and protective effects of HDL 2 , but not of HDL 3 , differed significantly between control and diabetic subjects. HDL 2 from diabetics were triglyceride enriched and cholesterol depleted compared with those from controls. Control HDL 2 inhibited LDL oxidation, as assessed by lipid peroxides and electrophoretic mobility, significantly (PϽ0.05) more than did diabetic HDL 2 in both the fasting and postprandial state. In addition, HDL 2 from diabetics did not protect against apolipoprotein B-100 fragmentation in LDL. Cross-linking in apolipoprotein A-I, oxidized in the presence of LDL, was extensive in HDL 2 from diabetics compared with that from controls. Serum triglyceride concentrations were negatively correlated with protection by HDL 2 (rϭϪ0.673, PϽ0.05) in diabetic but not in control subjects. HDL 2 -associated platelet-activating factor acetylhydrolase activity was positively correlated with protection by HDL 2 in control (rϭ0.872, PϽ0.002) but not in diabetic subjects.In conclusion, compositional alterations in HDL 2 from poorly controlled type 2 diabetic subjects may reduce its antiatherogenic properties.