12-Ketodeoxycholic acid is a metabolite of the secondary bile acid deoxycholic acid[1]. Bile acids are primarily synthesized from cholesterol in the liver and then secreted into the intestine through bile. In the intestine, some bile acids are metabolized by gut microbiota and reabsorbed into the liver through the enterohepatic circulation. Additionally, some bile acids and their metabolites are filtered by the kidneys and excreted in urine[2]. 12-Ketodeoxycholic acid can be used as potential metabolite biomarkers or therapeutic approaches for metabolic diseases such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD)[3][4]. The level changes of 12-Ketodeoxycholic acid can also serve as a biomarker for kidney injury[5]. 12-Ketodeoxycholic acid is usually used in the research of intestinal inflammation[6].
In vitro, treatment of LPS-stimulated 293T cells with 12-Ketodeoxycholic acid (50, 75, and 100µM; 24h) significantly reduced the levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α and increased anti-inflammatory IL-10 levels[7].
In vivo, 12-Ketodeoxycholic acid (50mg/kg/day; 7 days; oral administration) alleviated colonic inflammation, reduced the expression of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, increased anti-inflammatory IL-10 levels, and inhibited the mTORC1 signaling pathway in the colon of DSS-induced colitis mice[7].
References:
[1] Franco P, Porru E, Fiori J, et al. Identification and quantification of oxo-bile acids in human faeces with liquid chromatography-mass spectrometry: A potent tool for human gut acidic sterolbiome studies. J Chromatogr A. 2019;1585:70-81.
[2] Cai J, Rimal B, Jiang C, Chiang JYL, Patterson AD. Bile acid metabolism and signaling, the microbiota, and metabolic disease. Pharmacol Ther. 2022;237:108238.
[3] Xue J, Allaband C, Zuffa S, et al. Gut Microbiota and Derived Metabolites Mediate Obstructive Sleep Apnea Induced Atherosclerosis. Preprint. bioRxiv. 2024;2024.11.18.624205.
[4] Ahmad MI , Umair Ijaz M , Hussain M , et al. High fat diet incorporated with meat proteins changes biomarkers of lipid metabolism, antioxidant activities, and the serum metabolomic profile in Glrx1-/- mice. Food Funct. 2020;11(1):236-252.
[5] Chen H, Cao G, Chen DQ, et al. Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression. Redox Biol. 2016;10:168-178.
[6] Feng P, Li Q, Liu L, et al. Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability. Int J Mol Sci. 2022;23(7):3832.
[7] Zhang K, Xu Y, Zheng Y, et al. Bifidobacterium pseudolongum-Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP-PKG-mTORC1 Pathway. Adv Sci (Weinh). 2024;11(43):e2406917.
12-Ketodeoxycholic acid是次级胆汁酸脱氧胆酸（deoxycholic acid）的代谢产物[1]。胆汁酸主要在肝脏中由胆固醇合成，随后通过胆汁分泌到肠道。在肠道中，部分胆汁酸被肠道微生物群代谢，并通过肠肝循环重吸收回肝脏。此外，部分胆汁酸及其代谢产物会通过肾脏滤过并排泄到尿液中[2]。12-Ketodeoxycholic acid可以作为代谢性疾病（如动脉粥样硬化和非酒精性脂肪性肝病，NAFLD）的潜在代谢标志物或治疗手段[3][4]。12-Ketodeoxycholic acid的水平变化也可以作为肾脏损伤的标志物[5]。12-Ketodeoxycholic acid通常用于肠道炎症相关研究[6]。
在体外实验中，用 12-Ketodeoxycholic acid（ 50、75和100µM；24 小时）处理 LPS刺激的293T细胞，显著降低了促炎细胞因子IL-6、IL-1β和TNF-α的水平，并增加了抗炎细胞因子IL-10的水平[7]。
在体内实验中，12-Ketodeoxycholic acid（50mg/kg/天；连续给药7天；口服）显著减轻了DSS诱导的结肠炎小鼠的结肠炎症，降低了结肠中促炎细胞因子IL-6、IL-1β和TNF-α的表达，增加了抗炎细胞因子IL-10的水平，并抑制了mTORC1信号通路[7]。