Department of Surgery, School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.
BioMedical Research Institute, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
Int J Mol Sci. 2023 Aug 2;24(15):12333. doi: 10.3390/ijms241512333.
Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.
溃疡性结肠炎是一种炎症性肠病，其特征是结肠的黏膜和黏膜下层发生炎症。肥胖与结肠炎的发生和进展密切相关。将肥胖与结肠炎联系起来的最合理机制是与脂肪生成相关的过度炎症反应，导致黏膜功能障碍。肥胖和结肠炎通过几种发病机制联系在一起，包括过度脂肪生成、脂毒性、促炎脂肪因子/细胞因子、巨噬细胞极化、氧化应激、内质网（ER）应激和肠道微生物群。这些低水平的肠道炎症会导致黏膜层损伤，特别是通过粘蛋白 2（MUC2）错误折叠导致杯状细胞功能障碍，最终导致结肠炎。抑制炎症反应可能是治疗肥胖相关结肠炎最有效的方法。我们专注于短额负蝗幼虫中多酚的抗炎作用。短额负蝗被制备成低分子蛋白水解物（PHPB）以增加抗炎分子的浓度。在本研究中，我们研究了 PHPB 在肥胖诱导的结肠炎小鼠模型中的抗炎作用。与高脂肪饮食（HFD）组相比，用 PHPB 处理的组表现出体重/器官/脂肪重量减轻、食欲/食物摄入抑制、异位脂肪的降脂作用以及通过 AMPK 信号通路的抗脂肪生成机制。此外，我们观察到 PPARγ 和 C/EBPα 的表达减弱，促炎分子的抑制，抗炎分子的刺激，对肥胖相关肠道微生物群的益生菌样作用，对 M1 巨噬细胞极化的抑制，氧化/ER 应激的抑制，以及结肠中 Muc2 蛋白错误折叠的减少。这些不同的抗炎反应导致杯状细胞的组织学和功能恢复，最终改善结肠炎。因此，我们的研究结果表明，短额负蝗的蛋白水解物可以通过其抗炎活性改善肥胖相关结肠炎。
