Guo Changtong, Shi Xiangda, Luo Bingbing, Yang Yuxuan, Huang Jian, Xu Jiale, Zheng Rong, Jiang Siwen, Chai Jin
Agricultural Ministry Key Laboratory of Swine Breeding and Genetics & Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
Agricultural Ministry Key Laboratory of Swine Breeding and Genetics & Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
J Nutr Biochem. 2025 Oct;144:109955. doi: 10.1016/j.jnutbio.2025.109955. Epub 2025 Jun 2.
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 CRS. 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<.05), and extremely significantly decreased the feed intake and feed to gain ratio of CRS mice (P<.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<.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<.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<.01), extremely significantly increased the survival rate of inflammatory cells (P<.01) and the expression of tight junction proteins (P<.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.
在实际生产中，拥挤狭窄的空间以及抓捕、运输等操作所产生的束缚应激，会引发肠道炎症并影响动物生长性能，损害养殖场的经济效益。异戊酸作为一种短链脂肪酸（SCFA），已被发现有助于增强犊牛消化并抑制炎症因子的表达。在本研究中，我们首先构建了慢性束缚应激（CRS）小鼠模型，并给CRS小鼠喂食添加了异戊酸钠的日粮，以探究外源性添加异戊酸对CRS小鼠的缓解作用。随后利用仔猪空肠上皮细胞系-J2（IPEC-J2）构建炎症模型，模拟应激后的肠道炎症，探究异戊酸对炎症的缓解作用以及对肠道屏障的修复作用。结果显示，喂食异戊酸钠显著提高了CRS小鼠1-28天的体重增加量以及体重增长率（P<0.05），并极显著降低了CRS小鼠的采食量和料重比（P<0.01）。此外，喂食异戊酸钠改善了CRS所致小鼠器官指数的降低，并显著提高了CRS小鼠的腿部肌肉指数（P<0.05）。同时，喂食异戊酸钠改善了CRS小鼠的抑郁行为，并促进了其大脑和下丘脑5-羟色胺的分泌。此外，喂食异戊酸钠改善了CRS小鼠的肠道炎症，表现为结肠炎症因子表达极显著降低，紧密连接蛋白表达增加（P<0.01）。研究发现，添加异戊酸极显著降低了炎症细胞中炎症因子的表达以及NF-κB p65的磷酸化水平（P<0.01），极显著提高了炎症细胞的存活率（P<0.01）和紧密连接蛋白的表达（P<0.05），改善了炎症细胞的形态。添加短链脂肪酸受体GPR41和GPR43拮抗剂后，异戊酸对炎症的抵抗作用受到抑制。上述结果表明，异戊酸对小鼠CRS具有缓解作用，并通过抑制NF-κB激活发挥其抗炎作用。
