Monovalerin and trivalerin increase brain acetic acid, decrease liver succinic acid, and alter gut microbiota in rats fed high-fat diets

Thao Duy Nguyen, Olena Prykhodko, Frida Fåk Hållenius, Margareta Nyman

Short-chain fatty acids (SCFA) are known for their anti-inflammatory properties and may also prevent against the development of metabolic diseases. This study investigated possible effects of two valeric acid esters, monovalerin (MV) and trivalerin (TV) in rats fed high-fat diets. Four groups of rats were given a low-fat diet (LF) or a high-fat control diet (HFC) with or without supplementation of MV or TV (5 g/kg) for 3 weeks (n = 7/group). SCFA (caecum, blood, liver and brain), succinic acid (liver), microbiota (caecum), lipid profile (liver and blood) and the inflammatory biomarker, lipopolysaccharide-binding protein (blood) were analysed at the end of the experiment. Supplementation of MV and TV to a high-fat diet increased 1.5-fold the amounts of acetic acid in the brain and 1.7-fold serum concentration of valeric acid, whereas liver succinic acid was reduced by 1.5-fold. Although liver triglyceride levels were higher in both MV and TV groups compared with the LF group, liver LDL/HDL ratio was lower in the MV group (P < 0.05). The caecal microbiota composition was altered, with threefold higher abundance of Bacteroidetes and higher ratio of Bacteroidetes/Firmicutes in the MV group compared with the HFC and LF groups. Acetic acid in the brain was negatively correlated with TM7, family S24-7 and rc4-4, and positively associated to Tenericutes and Anaeroplasma. The present study shows that MV and TV in the specified dose can affect caecal microbiota composition and, therefore, bacterial metabolites in the liver, serum and brain as well as the lipid profile in the liver.