Isovaleric acid ameliorates chronic restraint stress and resists inflammation by inhibiting NF-κB activation in mice

In actual production, the restraint stress caused by crowded and narrow spaces, as well as operations such as capture and transportation, can lead to intestinal inflammation and affect animal growth performance, damaging the economic benefits of livestock farms. Isovaleric acid, a type of short-chain fatty acid (SCFA), has been found to be useful in enhancing calf digestion and inhibiting the expression of inflammatory factors. In this study, we first constructed a mouse model of chronic restraint stress (CRS) and fed a diet supplemented with sodium isovalerate to mice with CRS to investigate the mitigating effect of exogenously added isovalerate on mice with chronic restraint stress. An inflammation model was then constructed using piglet jejunal epithelial cell line-J2 (IPEC-J2) to simulate intestinal inflammation after stress, and to investigate the mitigating effect of isovaleric acid on inflammation as well as the repairing effect on intestinal barrier. The results showed that feeding sodium isovalerate significantly increased the weight gain as well as the body weight growth rate of CRS mice from 1-28 days ( P < 0.05), and extremely significantly decreased the feed intake and feed to gain ratio of CRS mice ( P < 0.01). In addition, feeding sodium isovalerate ameliorated the decrease in organ index in mice caused by CRS and significantly increased leg muscle index in CRS mice ( P < 0.05). Meanwhile, feeding sodium isovalerate improved depressive behavior and promoted 5-HT secretion in the brain and hypothalamus of CRS mice. Besides, feeding sodium isovalerate ameliorated intestinal inflammation in CRS mice, as evidenced by extremely significantly decreased the expression of colonic inflammatory factors and increased the expression of tight junction proteins ( P < 0.01). It was found that the addition of isovaleric acid extremely significantly reduced the expression of inflammatory factors and the phosphorylation level of NF-κB p65 in inflammatory cells ( P < 0.01), extremely significantly increased the survival rate of inflammatory cells ( P < 0.01) and the expression of tight junction proteins ( P < 0.05), improved the morphology of inflammatory cells. After the addition of short-chain fatty acid receptor GPR41 and GPR43 antagonists, the resistance effect of isovaleric acid on inflammation was inhibited. The above results suggest that isovaleric acid has an ameliorating effect on CRS in mice and inhibits NF-κB activation thereby exerting its anti-inflammatory effect.