Hepatic cholesterol accumulation ascribed to the activation of ileum Fxr-Fgf15 pathway inhibiting hepatic Cyp7a1 in high-fat diet-induced obesity rats

Duan, Yingting; Zhang, Fan; Wang, Yuan; Wei, Yuhui; Wei, Mengmeng; Zhou, Yan; Yang, Yuquan; Chang, Yae; Wu, Xinan

doi:10.1016/j.lfs.2019.116638

Cited by 46 publications

(30 citation statements)

References 43 publications

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“…All data are expressed as the mean ± SD, *p < 0.05, **p < 0.01, ***p < 0.001, ns > 0.05, Statistically significant differences (p value < 0.05) between the two groups were determined by Mann-Whitney U test in A, B, C, E, F, and H. Statistically significant differences (p value < 0.05) between groups were determined by Student's t test in Fig. 7 I and J cholesterol in the liver [28]. Decreases in gut microbiota in patients with gallstones can increase the hepatic cholesterol secretion [24], which may lead to oversaturation of bile cholesterol and induction of cholesterol stone formation.…”

Section: Discussionmentioning

confidence: 98%

Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

et al. 2020

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Background: The gut microbiota participates in the metabolism of substances and energy, promotes the development and maturation of the immune system, forms the mucosal barrier, and protects the host from pathogen attacks. Although the pathogenesis of cholesterol gallstones is still not clear, studies have suggested that gut microbiota dysbiosis plays an important role in their formation. Methods: Microbial DNA from faeces of normal control patients and those of patients with calculi was subjected to 16S rRNA gene sequencing to detect gene expression changes in intestinal microbes. ELISA kits were used to measure free bile acids, secondary bile acids and coprostanol according to the manufacturer's instructions. The relationship between flora and their metabolites was then analysed. Results: In the gallstone group, the diversity of intestinal bacteria and the abundances of certain phylogroups were significantly decreased (p < 0.05), especially Firmicutes (p < 0.05), the largest phylum represented by the gut microbiota. This study found an increase in free bile acids (p < 0.001) and secondary bile acids (p < 0.01) in the enterohepatic circulation. Bile salt hydrolase activity was not related to the abundances of BSH-active bacteria. 7adehydroxylating gut bacteria were significantly increased (p < 0.01), whereas cholesterol-lowering bacteria were significantly reduced (p < 0.05). The Ruminococcus gnavus group could be used as a biomarker to distinguish the gallstone group from the control group. Conclusion: We conclude that intestinal flora imbalance affects bile acid and cholesterol metabolism and is associated with gallstone formation.

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Section: Discussionmentioning

confidence: 98%

Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

et al. 2020

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“…Duan et al showed that the increase in bile acid uptake by intestinal epithelial cells could inhibit CYP7A1 through the FFX-FGF19 pathway. Since CYP7A1 is a key enzyme in cholesterol elimination, the inhibition of CYP7A1 could cause the accumulation of cholesterol in the liver [28]. Decreases in gut microbiota in patients with gallstones can increase the hepatic cholesterol secretion [24], which may lead to oversaturation of bile cholesterol and induction of cholesterol stone formation.…”

Section: Discussionmentioning

confidence: 99%

Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

Wang

Hao

Yao

et al. 2020

Preprint

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Background: The gut microbiota participates in the metabolism of substances and energy, promotes the development and maturation of the immune system, forms the mucosal barrier, and protects the host from pathogen attacks. Although the pathogenesis of cholesterol gallstones is still not clear, studies have suggested that gut microbiota dysbiosis plays an important role in their formation. Methods: Microbial DNA from faeces of normal control patients and those of patients with calculi was subjected to 16S rRNA gene sequencing to detect gene expression changes in intestinal microbes. ELISA kits were used to measure free bile acids, secondary bile acids and coprostanol according to the manufacturer’s instructions. The relationship between flora and their metabolites was then analysed. Results: In the gallstone group, the diversity of intestinal bacteria and the abundances of certain phylogroups were significantly decreased (p<0.05), especially Firmicutes (p<0.05), the largest phylum represented by the gut microbiota. This study found an increase in free bile acids (p<0.001) and secondary bile acids (p<0.01) in the enterohepatic circulation. Bile salt hydrolase activity was not related to the abundances of BSH-active bacteria. 7a-dehydroxylating gut bacteria were significantly increased (p<0.01), whereas cholesterol-lowering bacteria were significantly reduced (p<0.05). The Ruminococcus gnavus group could be used as a biomarker to distinguish the gallstone group from the control group. Conclusion: We conclude that intestinal flora imbalance affects bile acid and cholesterol metabolism and is associated with gallstone formation.

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“…TSG, emodin, and RES whose pharmacological activities are consistent with those of PMR all show antisteatosis, antiinflammatory, antifibrotic, and antioxidative stress activities and increase β-oxidation of fatty acids in mitochondria. Meanwhile, TSG and emodin can regulate bile acid metabolism by increasing the expression of CYP7A1, while RES can affect bile acid metabolism by regulating LXR and FXR genes which can adjust CYP7A1 indirectly [150]. Therefore, these three components may contribute to the activity of PMR in regulating bile acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

A Candidate Drug for Nonalcoholic Fatty Liver Disease: A Review of Pharmacological Activities of Polygoni Multiflori Radix

Zhou

Liu

et al. 2020

BioMed Research International

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Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients’ compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR.

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Hepatic cholesterol accumulation ascribed to the activation of ileum Fxr-Fgf15 pathway inhibiting hepatic Cyp7a1 in high-fat diet-induced obesity rats

Cited by 46 publications

References 43 publications

Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

A Candidate Drug for Nonalcoholic Fatty Liver Disease: A Review of Pharmacological Activities of Polygoni Multiflori Radix

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