Hyocholic acid (γ-Muricholic acid) is the major bile acid in pigs and other mammals and is also found in urine samples of patients with cholestasis[1]. Hyocholic acid promotes intracellular glucagon-like peptide-1 (GLP-1) secretion by activating G protein-coupled bile acid receptor (TGR5) and inhibiting farnesoid X receptor (FXR), thereby improving glucose homeostasis[2]. Hyocholic acid can be used as a novel biomarker for metabolic disorders and can resist type 2 diabetes[3].
In vitro, treatment of STC-1 and NCI-H716 cells with hyocholic acid (25, 50 μM) for 24 h upregulated GLP-1 protein secretion and proglucagon gene transcription in cells [4].
In vivo, oral treatment of diabetic mice with hyocholic acid (100 mg/kg) reduced blood glucose levels, increased fasting insulin levels, and upregulated serum GLP-1 levels through TGR5 and FXR signaling in vivo [4]. Oral treatment of nonalcoholic hepatitis mice with hyocholic acid (10, 100 mg/kg) for 16 weeks alleviated hepatic steatosis induced by a high-fat, high-cholesterol (HFHC) diet, reduced the production of lipid peroxides in a dose-dependent manner, and prevented hepatocyte apoptosis[5].
References:
[1] Lundell K, Wikvall K. Species-specific and age-dependent bile acid composition: aspects on CYP8B and CYP4A subfamilies in bile acid biosynthesis[J]. Current drug metabolism, 2008, 9(4): 323-331.
[2] Jia W, Rajani C, Zheng X, et al. Hyocholic acid and glycemic regulation: Comments on ‘Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism’[J]. Journal of Molecular Cell Biology, 2021, 13(6): 460-462.
[3] Zheng X, Chen T, Zhao A, et al. Hyocholic acid species as novel biomarkers for metabolic disorders[J]. Nature communications, 2021, 12(1): 1487.
[4] Zheng X, Chen T, Jiang R, et al. Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism[J]. Cell metabolism, 2021, 33(4): 791-803. e7.
[5] Xie Y, Shen F, He Y, et al. Gamma-muricholic acid inhibits nonalcoholic steatohepatitis: Abolishment of steatosis-dependent peroxidative impairment by FXR/SHP/LXRα/FASN signaling[J]. Nutrients, 2023, 15(5): 1255.
猪胆酸（Hyocholic Acid; γ-Muricholic Acid）是猪和其他哺乳动物的主要胆汁酸，也在胆汁淤积患者的尿液样本中发现[1]。Hyocholic Acid通过激活G蛋白偶联胆汁酸受体（TGR5）和抑制法尼醇X受体（FXR）促进细胞内胰高血糖素样肽-1（GLP-1）分泌，改善葡萄糖稳态[2]。Hyocholic Acid可作为代谢紊乱的新型生物标志物，可抵抗2型糖尿病[3]。
在体外，Hyocholic Acid（25, 50μM）处理STC-1和NCI-H716细胞24h，上调了细胞中的GLP-1蛋白分泌和胰高血糖素原基因转录[4]。
在体内，Hyocholic Acid（100mg/kg）通过口服治疗糖尿病模型小鼠，降低了血糖水平，升高了空腹胰岛素水平，通过体内TGR5和FXR信号传导上调了血清GLP-1水平[4]。Hyocholic Acid（10、100mg/kg）通过口服治疗非酒精性肝炎小鼠16周，可减轻由高脂肪高胆固醇（HFHC）饮食引起的肝脏脂肪变性，剂量依赖性地减少了脂质过氧化物的产生，阻止了肝细胞凋亡过程[5]。