Monobutyrin (MB) and monovalerin (MV),
esters of
short-chain fatty acids (SCFAs), have previously been shown to reduce liver
cholesterol and
inflammation in conventional rats fed high-fat diets. This study explored the potential effects of MB and MV in hypercholesterolemic
apolipoprotein E-knockout (
ApoE-/-) rats.
ApoE-/- rats were fed three high-fat (HF) diets, pure or supplemented with MB or MV (1%), for 5 weeks. One group of conventional rats (C) was also fed the pure high-fat diet and another group of
ApoE-/- rats a low-fat (LF) diet. Blood and liver
lipids, urinary
lactulose/
mannitol, SCFAs (blood and brain),
tight junction proteins (small intestine and brain), and
inflammation-related markers (blood, brain, and liver) were analyzed. MV supplementation elevated serum
high-density lipoprotein (
HDL) cholesterol and
valeric acid concentration (p < 0.05), while the amounts of
isovaleric acid in the brain were reduced (p < 0.05). MB increased
butyric acid amounts in the brain, while the plasma concentration of
interleukin 10 (IL-10) was lowered (p < 0.05). Both MV and MB upregulated the expression of
occludin and zonula occludens-1 (ZO-1) in the brain (p < 0.05). Supplementation of MB or MV affected
HDL cholesterol, the expression of
tight junction proteins, and SCFA profiles. MB and MV may therefore be promising supplements to attenuate
lipid metabolic disorders caused by high-fat intake and genetic deficiency.