Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, China.
Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, China.
J Nutr. 2024 Jul;154(7):2087-2096. doi: 10.1016/j.tjnut.2024.03.001. Epub 2024 Mar 6.
α-Ketoglutarate (AKG) plays a pivotal role in mitigating inflammation and enhancing intestinal health.
This study aimed to investigate whether AKG could protect against lipopolysaccharide (LPS)-induced intestinal injury by alleviating disorders in mitochondria-associated endoplasmic reticulum (MAM) membranes, dysfunctional mitochondrial dynamics, and endoplasmic reticulum (ER) stress in a piglet model.
Twenty-four piglets were subjected to a 2 × 2 factorial design with dietary factors (basal diet or 1% AKG diet) and LPS treatment (LPS or saline). After 21 d of consuming either the basal diet or AKG diet, piglets received injections of LPS or saline. The experiment was divided into 4 treatment groups [control (CON) group: basal diet + saline; LPS group: basal diet +LPS; AKG group: AKG diet + saline; and AKG_LPS group: AKG + LPS], each consisting of 6 piglets.
The results demonstrated that compared with the CON group, AKG enhanced jejunal morphology, antioxidant capacity, and the messenger RNA and protein expression of tight junction proteins. Moreover, it has shown a reduction in serum diamine oxidase activity and D-lactic acid content in piglets. In addition, fewer disorders in the ER-mitochondrial system were reflected by AKG, as evidenced by AKG regulating the expression of key molecules of mitochondrial dynamics (mitochondrial calcium uniporter, optic atrophy 1, fission 1, and dynamin-related protein 1), ER stress [activating transcription factor (ATF) 4, ATF 6, CCAAT/enhancer binding protein homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein (GRP) 78, and protein kinase R-like ER kinase], and MAM membranes [mitofusin (Mfn)-1, Mfn-2, GRP 75, and voltage-dependent anion channel-1].
Dietary AKG can prevent mitochondrial dynamic dysfunction, ER stress, and MAM membrane disorder, ultimately alleviating LPS-induced intestinal damage in piglets.
α-酮戊二酸（AKG）在减轻炎症和改善肠道健康方面发挥着关键作用。
本研究旨在通过减轻线粒体相关内质网（MAM）膜、功能失调的线粒体动力学和内质网（ER）应激紊乱，探讨 AKG 是否可以保护仔猪模型免受脂多糖（LPS）诱导的肠道损伤。
采用 2×2 因子设计，饮食因素（基础日粮或 1%AKG 日粮）和 LPS 处理（LPS 或生理盐水），共 24 头仔猪。在基础日粮或 AKG 日粮喂养 21d 后，仔猪接受 LPS 或生理盐水注射。实验分为 4 个处理组[对照组（CON）：基础日粮+生理盐水；LPS 组：基础日粮+LPS；AKG 组：AKG 日粮+生理盐水；AKG_LPS 组：AKG+LPS]，每组 6 头仔猪。
结果表明，与 CON 组相比，AKG 增强了空肠形态、抗氧化能力以及紧密连接蛋白的信使 RNA 和蛋白表达。此外，AKG 还降低了仔猪血清二胺氧化酶活性和 D-乳酸含量。此外，AKG 还减少了 ER-线粒体系统的紊乱，表现为 AKG 调节了线粒体动力学（线粒体钙单向转运蛋白、视神经萎缩 1、分裂 1 和动力相关蛋白 1）、ER 应激[激活转录因子（ATF）4、ATF6、CCAAT/增强子结合蛋白同源蛋白、真核起始因子 2α、葡萄糖调节蛋白（GRP）78 和蛋白激酶 R 样内质网激酶]和 MAM 膜[融合蛋白（Mfn）-1、Mfn-2、GRP75 和电压依赖性阴离子通道-1]关键分子的表达。
日粮 AKG 可预防线粒体动态功能障碍、ER 应激和 MAM 膜紊乱，最终缓解 LPS 诱导的仔猪肠道损伤。
