| Summary: | 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 (<i>p</i> < 0.05), while the amounts of isovaleric acid in the brain were reduced (<i>p</i> < 0.05). MB increased butyric acid amounts in the brain, while the plasma concentration of interleukin 10 (IL-10) was lowered (<i>p</i> < 0.05). Both MV and MB upregulated the expression of occludin and zonula occludens-1 (ZO-1) in the brain (<i>p</i> < 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.
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