Glycerol esters of butyric and valeric acids counteract diet-related disorders : Prevention of metabolic disturbances induced by high-fat intake

Sammanfattning: Short-chain fatty acids (SCFAs), gut metabolites formed from indigestible dietary components by the colonic microbiota, are associated with numerous health effects, and may be responsible for the beneficial effects, at least in part, associated with dietary fibre. High-fat diets are known to cause low-grade inflammation in the body, but SCFAs are suggested to counteract unfavourable effects induced by these types of diets. This project was conducted to investigate possible preventive effects of four glycerol esters of SCFAs – monobutyrin (MB), tributyrin (TB), monovalerin (MV) and trivalerin (TV) – in conventional and ApoE knockout (ApoE-/-) rats fed high-fat diets.Glycerol esters of SCFAs were added to high-fat diet (HF) at different doses from 1 to 15 g/kg and given to rats for 3 to 5 weeks. A group fed a low-fat (LF) diet was included as a reference. Lipid and SCFA profiles, caecal microbiota, intestinal permeability, expression of genes involved in bile acid synthesis, tight junction proteins, SCFA receptors and some inflammatory markers were analysed to evaluate possible nutritional effects of the glycerol esters.In conventional rats, glycerol esters produced no apparent change in caecal SCFA concentrations. However, all the glycerol esters (supplemented to high-fat diets based on butter), at a dose of 5 g/kg, reduced total liver cholesterol, LDL-cholesterol, the ratio of LDL-to-HDL-cholesterol, and succinic acid. Butyrins had stronger effects on liver lipids than valerins, especially MB, which decreased liver total cholesterol by 51% and significantly downregulated Cyp8b1 expression involved in bile acid synthesis. When supplemented to high-fat diets based on lard, this dose of MB also decreased total and LDL-cholesterol in blood, while liver HDL-cholesterol increased. The valerins, MV and TV, increased levels of serum valeric acid and brain acetic acid. For all the glycerol esters, caecal microbiota composition was shifted to lower relative abundances of bacteria associated with obesity and inflammation, although the monoforms showed a more distinct difference from the HF non-supplemented group. Increased doses of MB, 7.5 and 15 g/kg, resulted in consistent reduction in liver total cholesterol and triglycerides. Intestinal permeability was lower with the highest dose of MB compared with the non-supplemented HF group.In ApoE-/- rats, supplementation of MB or MV at a dose of 10 g/kg upregulated the expression of occludin and ZO-1 in the brain and increased the mucosal thickness in the small intestine. MB increased the content of butyric acid in the brain, lowered plasma IL-10 concentration, and tended to improve intestinal barrier function. With MV, serum concentrations of HDL-cholesterol and valeric acid increased, while the amount of isovaleric acid was reduced in the brain.The results support a preventive role of butyrins and valerins from lipid disorders, impaired intestinal barrier and inflammation caused by high-fat diets and genetic predisposition. Their use as dietary supplements in human nutrition may therefore be promising for preventing or counteracting metabolic disorders and related diseases.