School of Food Science, Washington State University, Pullman, WA, 99164, USA.
Department of Animal Science, Washington State University, Pullman, WA, 99164, USA.
Mol Nutr Food Res. 2021 Apr;65(7):e2000936. doi: 10.1002/mnfr.202000936. Epub 2021 Mar 15.
As a natural compound in foods, alpha-ketoglutarate (aKG) is one of the key metabolites maintaining energy homeostasis. This study examines the beneficial effects of dietary aKG against the development of experimental colitis and further explores the underlying molecular mechanisms.
Eight-week-old male C57BL/6 mice receive drinking water with or without 1% aKG for 4 weeks. At week 3, colitis is induced by 2.5% dextran sulfate sodium (DSS) for 7 days followed by 7 days recovery. Dietary aKG supplementation decreases DSS-induced body weight loss, gross bleeding, fecal consistency score, and disease activity index. In agreement, aKG supplementation restores DSS-associated colon shortening, ameliorated mucosal damage, and macrophage infiltration into colonic tissue, which are associated with suppressed gut inflammation and Wnt signaling, and improved epithelial structure. Consistently, aKG supplementation enhances M1 to M2 macrophage polarization and strengthens intestinal barrier function. Additionally, aKG supplementation elevates colonic aKG levels while decreasing 2-hydroxyglutarate levels, which increases oxidative instead of glycolytic metabolism.
aKG supplementation protects against epithelial damage and ameliorates DSS-induced colitis, which are associated with suppressed inflammation, Wnt signaling pathway, and glycolysis. Intake of foods enriched with aKG or aKG supplementation can be an alternative approach for the prevention or treatment of colitis that are common in Western societies.
α-酮戊二酸（aKG）作为食物中的天然化合物，是维持能量平衡的关键代谢物之一。本研究探讨了饮食中 aKG 对实验性结肠炎发展的有益作用，并进一步探讨了其潜在的分子机制。
8 周龄雄性 C57BL/6 小鼠连续 4 周饮用含或不含 1%aKG 的水。在第 3 周，用 2.5%葡聚糖硫酸钠（DSS）诱导结肠炎，持续 7 天，然后恢复 7 天。饮食中补充 aKG 可减少 DSS 诱导的体重减轻、大体出血、粪便稠度评分和疾病活动指数。一致地，aKG 补充剂可恢复 DSS 相关的结肠缩短、改善黏膜损伤和巨噬细胞浸润到结肠组织，这与抑制肠道炎症和 Wnt 信号通路以及改善上皮结构有关。一致地，aKG 补充剂增强了 M1 到 M2 巨噬细胞的极化并增强了肠道屏障功能。此外，aKG 补充剂增加了结肠 aKG 水平，同时降低了 2-羟戊二酸水平，从而增加了氧化而不是糖酵解代谢。
aKG 补充剂可防止上皮损伤并改善 DSS 诱导的结肠炎，这与炎症、Wnt 信号通路和糖酵解的抑制有关。摄入富含 aKG 的食物或补充 aKG 可能是预防或治疗西方社会常见的结肠炎的一种替代方法。
