Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats

Ion and water transport across the teleost Oncorhynchus mykiss gallbladder were studied in vivo by comparing flow and composition of hepatic bile, collected by chronic catheter, to volume and composition of terminally collected gallbladder bile. Differences in composition were comparable with those of other vertebrates, whereas bile flow (75 μl ⋅ kg− 1 ⋅ h− 1) was below values reported for endothermic vertebrates. The gallbladder concentrates bile acids five- to sevenfold and exhibits higher net Cl− than Na+ transport in vivo, in contrast to the 1:1 transport ratio from gallbladders under saline/saline conditions. Transepithelial potential (TEP) in the presence of bile, at the apical surface, was −13 mV (bile side negative) but +1.5 mV in the presence of saline. Bile acid in the apical saline reversed the TEP, presumably by a Donnan effect. We propose that ion transport across the gallbladder in vivo involves backflux of Na+ from blood to bile resulting in higher net Cl− than Na+ flux. This Na+backflux is driven by a bile side negative TEP and low Na+activity in bile due to the complexing effects of bile acids.

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FRI-107-Emerging role of taurine conjugated bile acids in the gut liver axis and on hepatic bile acid receptors in chronic hepatitis C

Journal of Hepatology ◽

10.1016/s0618-8278(19)30852-7 ◽

2019 ◽

Vol 70 (1) ◽

pp. e434-e435

Author(s):

Rabab Oun Ali Anwar Ali ◽

Gabriella quinn ◽

kareen hill ◽

Grace Zhang ◽

Christopher Koh ◽

...

Keyword(s):

Chronic Hepatitis ◽

Bile Acid ◽

Hepatitis C ◽

Bile Acids ◽

Chronic Hepatitis C ◽

Hepatic Bile ◽

Bile Acid Receptors ◽

Conjugated Bile Acids

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The inhibition of hepatic bile acids transporters Ntcp and Bsep is involved in the pathogenesis of isoniazid/rifampicin-induced hepatotoxicity

Toxicology Mechanisms and Methods ◽

10.3109/15376516.2015.1033074 ◽

2015 ◽

Vol 25 (5) ◽

pp. 382-387 ◽

Cited By ~ 25

Author(s):

Yao Xue Guo ◽

Xue Fei Xu ◽

Qi Zhi Zhang ◽

Chun Li ◽

Ye Deng ◽

...

Keyword(s):

Bile Acids ◽

Hepatic Bile ◽

Hepatic Bile Acids

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Abstract 296: Decreased Hepatic Avpr1a Gene Expression and Elevated Serum Bile Acid in Mouse Model of Metabolic Syndrome

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a296 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Xiaoya Ma ◽

Peter F Bodary

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Bile Acid ◽

Bile Acids ◽

Serum Bile Acid ◽

Hepatic Gene Expression ◽

Serum Bile Acids ◽

Kk Mice ◽

The Metabolic Syndrome

The KK/HIJ mouse has been demonstrated to have polygenic obesity and insulin resistance and serve as a model of metabolic syndrome. From microarray studies in this mouse strain, we observed hepatic gene expression of arginine vasopressin receptor 1A (Avpr1a) as the most differentially elevated gene in the liver following 3-week of voluntary wheel running activity. Subsequent studies validated that hepatic Avpr1a gene expression is significantly upregulated following voluntary activity and also highly suppressed (4 to 8-fold) in 2 independent models of insulin resistance (including obesity and lipoatrophic models). Although Avpr1a is highly abundant in the liver, its physiologic role is not well described. One proposed role for hepatic Avpr1a is mediation of vasopressin-induced bile acid secretion. To further evaluate the relationship between hepatic Avpr1a and bile acid homeostasis, we determined the age-related change in these variables in female KK mice. To investigate, adipose tissue, liver and serum were collected from female KK mice from before sexual maturity (PRE: 4.5 weeks old, n=9) and after sexual maturation (POST: 6 to 30 weeks old, n=12). Consistent with previous studies using this obesity-prone strain, we observed a robust increase in adiposity with age despite a standard rodent chow diet. RT-PCR studies of hepatic gene expression revealed a 53% lower Avpr1a in POST compared to PRE mice (p<0.00001). In parallel with the drop in hepatic Avpr1a gene expression was an increase in serum bile acids (PRE: 26.56± 9.98μmol/L; POST: 39.40± 9.63μmol/L; p<0.01). A negative correlation was evident between hepatic Avpr1a gene expression and serum bile acid level (R= -0.51). The change in Avpr1a and bile acids was pronounced at the age of onset of estrous cycling. In conclusion, female KK mice have a significant increase in fat mass with age in parallel with an elevation of serum bile acids and downregulation of hepatic Avpr1a gene expression. We propose that suppression of hepatic Avpr1a increases hydrophobic bile acids in the liver and serum and promotes hepatic inflammation, contributing to symptoms of the metabolic syndrome.

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A9 BACTERIAL BILE SALT HYDROLASE GENE ABUNDANCE IS ASSOCIATED WITH RORC GENE EXPRESSION IN INTESTINAL MUCOSA OF INFLAMMATORY DISEASE PATIENTS

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.008 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 11-12

Author(s):

C Hernandez-Rocha ◽

K Borowski ◽

W Turpin ◽

M Smith ◽

J Stempak ◽

...

Keyword(s):

Gene Expression ◽

Bile Acid ◽

Bile Acids ◽

Acid Metabolism ◽

Bile Acid Metabolism ◽

Bile Salt Hydrolase ◽

Host Gene Expression ◽

Biopsy Site ◽

Endoscopic Score

Abstract Background The role of gut microbes involved in bile acid metabolism and their impact on mucosal immune regulation is beginning to be appreciated. For instance, changes in microbial bile salt hydrolase (BSH) activity which deconjugates bile acids in the gastrointestinal tract of gnotobiotic mice, significantly alters gene expression patterns of immune-related genes in ileum. Moreover, bile acid dysmetabolism may participate in the chronic inflammation loop of Inflammatory bowel disease (IBD). Aims We carried out an integrated mucosal microbiome-transcriptome analysis to elucidate associations between microbial bile-acid metabolizing function and host gene expression. Methods Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) patients were recruited prior to scheduled colonoscopy performed as part of clinical care. Only patients with non-inflamed mucosa defined as a segmental simple endoscopic score 0–2 in CD and a segmental Mayo endoscopic score of 0 in UC/IBDU were included in this analysis to minimize the effect of inflammation on gene expression. Biopsy samples were obtained from terminal ileum, ascending colon and sigmoid colon, and microbial DNA and human RNA was extracted. V4 region of 16S rRNA gene was sequenced and the relative abundance of bile acid-metabolizing genes was inferred using PICRUSt. RNA-seq was used to sequence total human RNA and a supervised transcript reduction analysis focus upon 65 genes previously associated with bile acid metabolism and IBD was utilized. Associations between microbiome clusters of orthologous groups (COGs), transcriptome, diagnosis (CD vs UC/IBDU), and biopsy site were analyzed using linear mixed-effects model with lmer4 function in R. An adjusted-p value after false discovery rate correction < 0.05 was considered significant. Results A total of 126 samples from 86 subjects were analyzed corresponding to 35 CD and 51 UC/IBDU. Mean age for the total cohort was 34.7 ± 11 years and 35 (40.6%) were females. There was a significant negative correlation between relative abundance of bacterial bsh genes (COG3049) and human RORC gene (p < 0.03). This association was independent of type of diagnosis and biopsy site. There was no association among other analyzed bacterial COGs and host genes. Conclusions Using an integrative microbiome-host transcriptome approach, our data provide new evidence linking microbial bile acid deconjugation (bsh genes) and host gene expression in the mucosal-luminal interface in quiescent IBD-affected tissue. Nuclear receptor RORC is pivotal in the differentiation and function of innate lymphoid cells and T-helper 17 cells. Modulation of this pathway by bile acids or gut bacteria involved in their metabolism could shed light on the immune role of bile acids in IBD patients. Funding Agencies CAG, CIHRNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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