Hyocholic Acid
(Synonyms: 猪胆酸,γ-Muricholic Acid) 目录号 : GC40717
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。
Cas No.:547-75-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | STC-1 and NCI-H716 cells |
Preparation Method | Cells were treated with different concentrations (5, 25, and 50μM) of Hyocholic Acid with 24h treatment for determination of GLP-1 secretion and proglucagon transcription. |
Reaction Conditions | 5, 25, 50μM; 24h |
Applications | Hyocholic Acid upregulates GLP-1 protein secretion and proglucagon gene transcription in STC-1 and NCI-H716 cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | C57BL/6 mice were randomized into the normal control (NC), NASH, NASH+vehicle, NASH+10mg/kg Hyocholic Acid, and NASH+100mg/kg Hyocholic Acid groups, respectively. Except for those in the NC group with a normal diet, all the mice were exposed to the high-fat high-cholesterol(HFHC) diet (2% cholesterol, 10% lard, and 88% normal diet) for 16 weeks. |
Dosage form | 10、100mg/kg; p.o. |
Applications | Hyocholic Acid attenuated rodent liver steatosis induced by the HFHC diet. Hyocholic Acid treatment dose-dependently reduced the production of lipid peroxides. Hyocholic Acid treatment dose-dependently prevented hepatocytes from the apoptotic process. |
References: [1]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. [2]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. | |
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]。
| Cas No. | 547-75-1 | SDF | |
| 别名 | 猪胆酸,γ-Muricholic Acid | ||
| 化学名 | (5β)-3α,6α,7α-trihydroxy-cholan-24-oic acid | ||
| Canonical SMILES | C[C@H](CCC(O)=O)[C@@]1([H])CC[C@@]2([H])[C@]3([H])[C@H](O)[C@H](O)[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@@]21C | ||
| 分子式 | C24H40O5 | 分子量 | 408.6 |
| 溶解度 | 30 mg/ml in DMF, 20 mg/ml in DMSO, 20 mg/ml in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4474 mL | 12.2369 mL | 24.4738 mL |
| 5 mM | 0.4895 mL | 2.4474 mL | 4.8948 mL |
| 10 mM | 0.2447 mL | 1.2237 mL | 2.4474 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Hyocholic Acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism
Cell Metab 2021 Apr 6;33(4):791-803.e7.PMID:33338411DOI:10.1016/j.cmet.2020.11.017.
Hyocholic Acid (HCA) and its derivatives are found in trace amounts in human blood but constitute approximately 76% of the bile acid (BA) pool in pigs, a species known for its exceptional resistance to type 2 diabetes. Here, we show that BA depletion in pigs suppressed secretion of glucagon-like peptide-1 (GLP-1) and increased blood glucose levels. HCA administration in diabetic mouse models improved serum fasting GLP-1 secretion and glucose homeostasis to a greater extent than tauroursodeoxycholic acid. HCA upregulated GLP-1 production and secretion in enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor (FXR), a unique mechanism that is not found in other BA species. We verified the findings in TGR5 knockout, intestinal FXR activation, and GLP-1 receptor inhibition mouse models. Finally, we confirmed in a clinical cohort, that lower serum concentrations of HCA species were associated with diabetes and closely related to glycemic markers.
Hyocholic Acid species as novel biomarkers for metabolic disorders
Nat Commun 2021 Mar 5;12(1):1487.PMID:33674561DOI:10.1038/s41467-021-21744-w.
Hyocholic Acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities.
Decreased Hyocholic Acid and Lysophosphatidylcholine Induce Elevated Blood Glucose in a Transgenic Porcine Model of Metabolic Disease
Metabolites 2022 Nov 23;12(12):1164.PMID:36557202DOI:10.3390/metabo12121164.
(1) Background: This work aims to investigate the metabolomic changes in PIGinH11 pigs and investigate differential compounds as potential therapeutic targets for metabolic diseases. (2) Methods: PIGinH11 pigs were established with a CRISPR/Cas9 system. PNPLA3I148M, hIAPP, and GIPRdn were knocked in the H11 locus of the pig genome. The differential metabolites between and within groups were compared at baseline and two months after high-fat-high-sucrose diet induction. (3) Results: 72.02% of the 815 detected metabolites were affected by the transgenic effect. Significantly increased metabolites included isoleucine, tyrosine, methionine, oxoglutaric acid, acylcarnitine, glucose, sphinganines, ceramides, and phosphatidylserines, while fatty acids and conjugates, phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins were decreased. Lower expression of GPAT3 and higher expression of PNPLA3I148M decreased the synthesis of diacylglycerol and phosphatidylcholines. Accumulated ceramides that block Akt signaling and decrease Hyocholic Acid and lysophosphatidylcholines might be the main reason for increased blood glucose in PIGinH11 pigs, which was consistent with metabolomic changes in patients. (4) Conclusions: Through serum metabolomics and lipidomics studies, significant changes in obesity and diabetes-related biomarkers were detected in PIGinH11 pigs. Excessive fatty acids β-oxidation interfered with glucose and amino acids catabolism and reduced phosphatidylcholines. Decreased Hyocholic Acid, lysophosphatidylcholine, and increased ceramides exacerbated insulin resistance and elevated blood glucose. Phosphatidylserines were also increased, which might promote chronic inflammation by activating macrophages.
Increased glycine-amidated Hyocholic Acid correlates to improved early weight loss after sleeve gastrectomy
Surg Endosc 2018 Feb;32(2):805-812.PMID:28779240DOI:10.1007/s00464-017-5747-y.
Background: Bile acids (BAs) are post-prandial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure. Total and glycine-amidated BAs increase after sleeve gastrectomy (SG) and correlate to improved metabolic disease. No specific bile acid subtype has been shown conclusively to mediate the weight loss effect. Therefore, the objective of this study was to prospectively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response. Methods: Patients were prospectively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity. Primary and secondary plasma bile acids and their amidated (glycine, G-, or taurine, T-) subtypes were measured at fasting, 30 and 60 min after a liquid meal performed pre-op, and at 6 and 12 weeks post-op. Area under the curve (AUC) was calculated for the hour meal test for each bile acid subtype. BAs that were significantly increased post-op were correlated to body mass index (BMI) loss. Results: Total BA AUC was significantly increased at 6 (p < 0.01) and 12 weeks post-op (p < 0.01) compared to pre-operative values. The increase in total BA AUC was due to a statistically significant increase in G-BAs. Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op. Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss (p = 0.03). Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 (p = 0.05) and 12 weeks (p = 0.006). Conclusions: SG induced an early and persistent post-prandial surge in multiple bile acid subtypes. Increased G-hyocholic consistently correlated with greater early BMI loss. This study provides evidence for a role of BAs in the surgical weight loss response after SG.
Effect of Hyocholic Acid on the prevention and dissolution of biliary cholesterol crystals in mice
Can J Physiol Pharmacol 1988 Aug;66(8):1028-34.PMID:3179836DOI:10.1139/y88-168.
Gallstone prevention and dissolution were studied in a mouse model of cholesterol cholelithiasis using Hyocholic Acid (3 alpha, 6 alpha, 7 alpha-trihydroxy-5 beta-cholanic acid). Addition of Hyocholic Acid, 0.1 or 0.3%, in the lithogenic diet (1% cholesterol + 0.5% cholic acid) prevented the formation of cholesterol monohydrate crystals in 70 and 90% of cases, respectively. On the other hand, chow diet supplemented with 0.1 or 0.3% Hyocholic Acid dissolved cholesterol crystals in lithiasic mice in, respectively, 80 and 100% of cases within 12 days. In both protocols, biles were largely supersaturated with cholesterol; lecithin-cholesterol lamellar liquid crystals were responsible for the transport of the excess cholesterol content. The percentage of hydrophilic bile salts (Hyocholic Acid, hyodeoxycholic acid, beta-muricholic acid) in bile, although moderate (15-50% of total bile salts), appears to induce such liquid crystalline dispersion. This study demonstrates that the balance between hydrophilic and hydrophobic bile salts plays a major role in the prevention and dissolution of cholesterol crystals. It is also shown that the desaturation of biliary cholesterol is not a prerequisite for gallstone dissolution.