Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients

Wu, Tao; Yang, Moon-Sik; Xu, Hanchen; Wang, Lei; Wei, Huafeng; Ji, Guang

doi:10.1021/acs.jproteome.1c00104

Cited by 21 publications

(11 citation statements)

References 63 publications

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“…A large number of patients are diagnosed with NAFLD, and the identification of patients who can easily develop LC or HCC is very important. BA has good utility in assessing NAFLD progression in patients with T2DM ( Wu et al, 2021 ), but BA is rarely studied in diagnostic models of NAFLD. BA profiles show significant differences in patients with chronic liver diseases with different causes ( Sang et al, 2021 ), suggesting the clinical potential of BA profiles in the differentiation of liver injury types.…”

Section: Prospects and Summarymentioning

confidence: 99%

The role of bile acid metabolism in the occurrence and development of NAFLD

Bing

2022

Front. Mol. Biosci.

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Non-alcoholic fatty liver disease (NAFLD) has become one of the important causes of cirrhosis and liver cancer, resulting in a huge medical burden worldwide. Currently, effective non-invasive diagnostic indicators and drugs for NAFLD are still lacking. With the development of metabolomics technology, the changes in metabolites during the development of NAFLD have been gradually revealed. Bile acid (BA) is the main endpoint of cholesterol metabolism in the body. In addition, it also acts as a signaling factor to regulate metabolism and inflammation in the body through the farnesyl X receptor and G protein-coupled BA receptor. Studies have shown that BA metabolism is associated with the development of NAFLD, but a large number of animal and clinical studies are still needed. BA homeostasis is maintained through multiple negative feedback loops and the enterohepatic circulation of BA. Recently, treatment of NAFLD by interfering with BA synthesis and metabolism has become a new research direction. Here, we review the changes in BA metabolism and its regulatory mechanisms during the development of NAFLD and describe the potential of studies exploring novel non-invasive diagnostic indicators and therapeutic targets for NAFLD based on BA metabolism.

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Section: Prospects and Summarymentioning

confidence: 99%

The role of bile acid metabolism in the occurrence and development of NAFLD

Bing

2022

Front. Mol. Biosci.

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“…The serum concentration of BAs was measured using a Waters ACQUITY ultraperformance liquid chromatography (UPLC) (BEH C18 1.7 μm 2.1 mm × 100 mm column) system coupled with Waters Xevo Triple Quadrupole mass spectrometry (TQ/MS) according to previously reported methods. − …”

Section: Materials and Methodsmentioning

confidence: 99%

Serum Bile Acid Metabolites Predict the Therapeutic Effect of Mesalazine in Patients with Ulcerative Colitis

et al. 2023

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Ulcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.

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“…All mice’s blood were centrifuged (3000 r/min, 15 min, 4°C), and serum and 50 mg tissue were stored at −80°C refrigerator for further analysis. Quantitative assessment of BAs is performed by laboratory-developed test kit-Metabolite Array (HMI, Shenzhen, Guangdong, China), according to previously reported methods ( Lu et al, 2020 ; Wu et al, 2021 ). BAs were quantified by ultra-performance liquid chromatography coupled to a tandem mass spectrometry system (UPLC/MS/MS, ACQUITY UPLC-Xevo TQ-S, Waters Corp, Milford, MA, United States).…”

Section: Methodsmentioning

confidence: 99%

Kaempferol attenuates nonalcoholic steatohepatitis by regulating serum and liver bile acid metabolism

Lü

Shao²,

Zhang³

et al. 2022

Front. Pharmacol.

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Objective: Changes in bile acids (BAs) are increasingly recognized as potential targets for non-alcoholic steatohepatitis (NASH). Kaempferol has been proved to be anti-inflammatory and reduce the disorder of lipid metabolism. In order to analyze the BA profile in NASH mice and determine the predictive biomarkers of kaempferol treatment, serum-targeted metabolomics and liver tissue RNA sequencing (RNA-seq) were carried out.Design: Six normal control mice (NC group), eight HFD-fed mice (HFD group), and eight kaempferol-treated HFD-fed mice (HFD + KP group) were included in the present study. Ultra-performance liquid chromatography coupled to a tandem mass spectrometry system (UPLC-MS/MS) was used to quantify serum and liver BAs, and RNA-seq was used to quantify liver differentially expressed genes related to BA metabolism.Results: The serum levels of CA, βMCA, UDCA, and 12-DHCA, as well as ωMCA in both the serum and liver, were significantly decreased in the HFD group compared with those in the NC group, and kaempferol can increase the serum levels of βMCA, UDCA, and ωMCA and the liver level of 12-DHCA. The serum levels of TDCA, THDCA, TUDCA, TDCA/CA, and TDCA/DCA were significantly increased in the HFD group compared with those of the NC group, and kaempferol can decrease them. Furthermore, NASH mice had a higher liver level of total CA%, total CDCA%, primary BAs/secondary BAs, 12α-OH BAs/non-12α-OH Bas, and conjugated BAs/unconjugated BAs, and all decreased after kaempferol treatment. According to the RNA-seq results, we found that compared with the NC group, the mRNA expression of cholesterol-7α-hydroxylase (CYP7A1) in the HFD group was significantly increased, and the mRNA expression of sterol 12α‐hydroxylase (CYP8B1) and multidrug resistance-related protein 3 (MRP3) was significantly decreased, while kaempferol significantly promoted the mRNA expression of mitochondrial sterol 27-hydroxylase (CYP27A1) and Na+ -taurocholate cotransporting polypeptide (NTCP).Conclusion: βMCA, CA, UDCA, 12-DHCA, ωMCA, CDCA, TωMCA, TDCA, THDCA, TCDCA, and TUDCA in the serum, as well as 6,7-diketoLCA, 12-DHCA, and ωMCA in the liver, may be potential biomarkers for kaempferol to improve NASH. HFD-induced NASH may be associated with the increase of CYP7A1 and the decrease of CYP8B1, leading to increased BA synthesis, and the decrease of MRP3 leading to decreased BA synthesis, and kaempferol may alleviate NASH by increasing CYP27A1 and NTCP to enhance BA transport.

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Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients

Cited by 21 publications

References 63 publications

The role of bile acid metabolism in the occurrence and development of NAFLD

The role of bile acid metabolism in the occurrence and development of NAFLD

Serum Bile Acid Metabolites Predict the Therapeutic Effect of Mesalazine in Patients with Ulcerative Colitis

Kaempferol attenuates nonalcoholic steatohepatitis by regulating serum and liver bile acid metabolism

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