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https://www.readbyqxmd.com/read/29452137/aryl-hydrocarbon-receptor-ahr-mediated-short-term-effects-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-on-bile-acid-homeostasis-in-wild-type-and-ahr-null-mice
#1
Iván L Csanaky, Andrew J Lickteig, Curtis D Klaassen
The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in male and female wild-type and AhR-null mice shortly after 4-day exposure, rather than at a later time when secondary non-AhR dependent effects are more likely to occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD decreased the concentration of total-(Σ) BAs in liver by approximately 50% (all major BA categories except for the non-6,12-OH BAs), without decreasing the expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the major BA regulatory pathways (FXR) in liver and intestine...
February 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29446652/developmental-regulation-of-the-intestinal-fgf19-system-in-domestic-pigs
#2
Aleix Gavaldà-Navarro, Jose J Pastor, Alessandro Mereu, Francesc Villarroya, Ignacio R Ipharraguerre
Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor involved in the regulation of bile acid homeostasis and energy metabolism in rodents and humans. In pigs, however, the FGF19 system remains largely unexplored. This study was designed to investigate the developmental regulation of the FGF19 system in domestic pigs. Samples of intestinal sections, liver, and plasma were collected from 24 pigs (n = 6) at four developmental stages (birth, pre-weaning, post-weaning, and adulthood). In the intestine, expression of the farnesoid X receptor (FXR) and FGF19 showed a congruent time- and region-dependent regulation, beginning soon after birth to achieve maximal expression in ileum during adulthood...
February 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29429758/the-immunobiology-of-mucosal-associated-invariant-t-cell-mait-function-in-primary-biliary-cholangitis-regulation-by-cholic-acid-induced-interleukin-7
#3
Xiang Jiang, Min Lian, Yanmei Li, Weici Zhang, Qixia Wang, Yiran Wei, Jun Zhang, Weihua Chen, Xiao Xiao, Qi Miao, Zhaolian Bian, Dekai Qiu, Jingyuan Fang, Aftab A Ansari, Patrick S C Leung, Ross L Coppel, Ruqi Tang, M Eric Gershwin, Xiong Ma
Mucosal-associated invariant T (MAIT) cells are novel innate-like T cells constituting a significant proportion of circulating and hepatic T cells. Herein, we extensively examine the phenotypical and functional alterations of MAIT cells and their regulation in a cohort of 56 patients with Primary Biliary Cholangitis (PBC) and 53 healthy controls (HC). Additionally alterations of MAIT cells were assessed before and after UDCA treatment. Finally the localization of MAIT cell in liver was examined using specific tetramer staining and the underlying mechanisms of these alterations in PBC were explored...
February 8, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29427579/protective-effects-of-yangonin-from-an-edible-botanical-kava-against-lithocholic-acid-induced-cholestasis-and-hepatotoxicity
#4
Yulong Kong, Xiaoguang Gao, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Pengyuan Sun, Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice...
February 7, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29404501/effect-of-combined-farnesoid-x-receptor-agonist-and-angiotensin-ii-type-1-receptor-blocker-on-hepatic-fibrosis
#5
Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Yasushi Okura, Naotaka Shimozato, Shinya Sato, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Yasuhiko Sawada, Takemi Akahane, Soichiro Saikawa, Keisuke Nakanishi, Takuya Kubo, Masanori Furukawa, Ryuichi Noguchi, Kiyoshi Asada, Koh Kitagawa, Takahiro Ozutsumi, Yuki Tsuji, Daisuke Kaya, Yukihisa Fujinaga, Hitoshi Yoshiji
The farnesoid X receptor (FXR) agonist, a bile acid-activated nuclear receptor, has been shown to improve the histologic features of nonalcoholic steatohepatitis (NASH); however, a satisfactory effect on hepatic fibrosis has not been achieved. We aimed to investigate the combined effect of FXR agonist and angiotensin II type 1 receptor blocker on hepatic fibrogenesis in rat models of NASH. For 8 weeks, two rat models of NASH were developed. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered intraperitoneal injections of 1 mL/kg pig serum (PS) twice a week, whereas Fischer-344 rats were fed a choline-deficient, L-amino acid-defined diet (CDAA)...
November 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29382564/diabetic-cognitive-dysfunction-is-associated-with-increased-bile-acids-in-liver-and-activation-of-bile-acid-signaling-in-intestine
#6
Xue Wang, Fangyu Wang, Yidan Zhang, Hui Xiong, Yanjun Zhang, Pengwei Zhuang, Youcai Zhang
Impaired regulation of bile acid (BA) homeostasis has been suggested to be associated with adverse metabolic consequences. However, whether BA homeostasis is altered in diabetes-induced cognitive dysfunction (DCD) remains unknown. In the present study, mice were divided into four groups, namely normal control (NC) group, high-fat diet (HFD) group, diabetes without cognitive dysfunction (unDCD) group, and DCD group. Compared to HFD mice, the concentration of total BAs in liver was higher in unDCD and DCD mice, due to increased intestinal BA absorption...
January 27, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29381405/the-influences-of-cholecystectomy-on-the-circadian-rhythms-of-bile-acids-as-well-as-the-enterohepatic-transporters-and-enzymes-systems-in-mice
#7
Fan Zhang, Yingting Duan, Lili Xi, Mengmeng Wei, Axi Shi, Yan Zhou, Yuhui Wei, Xinan Wu
Bile acids (BAs), the most important endogenous and signaling molecules regulate the target transporters and enzymes at transcriptional level, participate in a wide variety of processes throughout the entire gastrointestinal tract to orchestrate homeostasis in vivo. BAs and their metabolism and transportation appear to follow the clear circadian rhythms, and they are recently proposed also as the potential chronobiological signals that can affect the molecular clock mechanism. Cholecystectomy are believed to affect the circadian rhythms of BAs and the relevant enterohepatic transporters and enzymes systems and their regulatory signaling pathways, for the reason that the circadian cycle of gallbladder filling and emptying play a pivotal role in controlling the flow of bile into the intestine and the enterohepatic circulation of BAs...
January 30, 2018: Chronobiology International
https://www.readbyqxmd.com/read/29377207/farnesoid-x-receptor-signaling-activates-the-hepatic-x-box-binding-protein-1-pathway-in-vitro-and-in-mice
#8
Xiaoying Liu, Grace L Guo, Bo Kong, David B Hilburn, Susan C Hubchak, Seong Park, Brian LeCuyer, Antony Hsieh, Li Wang, Deyu Fang, Richard M Green
Bile acids are endogenous ligands of the nuclear receptor farnesoid X receptor (FXR), and pharmacologic FXR modulators are under development for the treatment of several liver disorders. The inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the unfolded protein response (UPR) is a protective cellular signaling pathway activated in response to endoplasmic reticulum stress. We investigated the role of FXR signaling in the activation of the hepatic XBP1 pathway. Mice were treated with deoxycholic acid (DCA), cholestyramine, GW4064 or underwent bile duct ligation (BDL) and the hepatic UPR activation was measured...
January 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29375205/int-767-improves-histopathological-features-in-a-diet-induced-ob-ob-mouse-model-of-biopsy-confirmed-non-alcoholic-steatohepatitis
#9
Jonathan D Roth, Michael Feigh, Sanne S Veidal, Louise Kd Fensholdt, Kristoffer T Rigbolt, Henrik H Hansen, Li C Chen, Mathieu Petitjean, Weslyn Friley, Niels Vrang, Jacob Jelsing, Mark Young
AIM: To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis (NASH). METHODS: The effects of INT-767 on histological features of NASH were assessed in two studies using Lepob/ob (ob/ob) NASH mice fed the AMLN diet (high fat with trans-fat, cholesterol and fructose). In a proof-of-concept study, Lepob/ob (ob/ob) NASH mice were first dosed with INT-767 (3 or 10 mg/kg for 8 wk)...
January 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29367104/farnesoid-x-receptor-antagonist-exacerbates-dyslipidemia-in-mice
#10
Yuichiro Amano, Hiroko Yamakawa, Kazuko Yonemori, Mitsuyuki Shimada, Ryuichi Tozawa
BACKGROUND: The effects of farnesoid X receptor (FXR) antagonists on plasma lipid profile in mice have not been investigated thus far. The aim of this study was to investigate the antidyslipidemic effects of an FXR antagonist in dyslipidemic mice, and to clarify the mechanisms underlying the lipid modulatory effect. METHODS: Compound-T0 (1-100 mg/kg) was orally administered to C57BL/6J mice fed a Western-type diet or low-density lipoprotein receptor knockout (LDLR-/-) mice fed a Western-type diet for a week, and plasma lipid levels were investigated...
July 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29365494/effect-of-bile-acid-receptor-fxr-tgr5-agonist-int-767-on-peripheral-immune-cells
#11
Zuzana Papackova, Marie Heczkova, Helena Dankova, Monika Cahova
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29361497/reversal-of-metabolic-disorders-by-pharmacological-activation-of-bile-acid-receptors-tgr5-and-fxr
#12
Kavita Jadhav, Yang Xu, Yanyong Xu, Yuanyuan Li, Jiesi Xu, Yingdong Zhu, Luciano Adorini, Yoon Kwang Lee, Takhar Kasumov, Liya Yin, Yanqiao Zhang
OBJECTIVES: Activation of the bile acid (BA) receptors farnesoid X receptor (FXR) or G protein-coupled bile acid receptor (GPBAR1; TGR5) improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. METHODS: Wild-type (WT), Tgr5-/-, Fxr-/-, Apoe-/- and Shp-/- mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders...
January 11, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29360226/modulation-of-transport-and-metabolism-of-bile-acids-and-bilirubin-by-chlorogenic-acid-against-hepatotoxity-and-cholestasis-in-bile-duct-ligation-rats-involvement-of-sirt1-mediated-deacetylation-of-fxr-and-pgc-1%C3%AE
#13
Lili Zhu, Lei Wang, Fei Cao, Peng Liu, Haidong Bao, Yumei Yan, Xin Dong, Dong Wang, Zhongyu Wang, Peng Gong
PURPOSE: To investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). METHODS: Rats received vehicle or CA (20, 50, or 100 mg/kg/d) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. RESULTS: After BDL, plasma levels of ALT, AST, total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology...
January 23, 2018: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/29356312/cenicriviroc-a-cytokine-receptor-antagonist-potentiates-all-trans-retinoic-acid-in-reducing-liver-injury-in-cholestatic-rodents
#14
Dongke Yu, Shi-Ying Cai, Albert Mennone, Pamela Vig, James L Boyer
BACKGROUND & AIMS: Cholestatic liver injury is mediated by bile acid induced inflammatory responses. We hypothesized that superior therapeutic effects might be achieved by combining treatments that reduce the bile acid pool size with one that blocks inflammation. METHODS: Bile duct ligated (BDL) rats and Mdr2(Abcb4)-/- mice were treated with all-trans retinoic acid (atRA), a potent inhibitor of bile acid synthesis, 5mg/kg/day by gavage, or Cenicriviroc (CVC), a known antagonist of CCR2 and CCR5, 50mg/kg/day alone or in combination for 14-day and one month, respectively...
January 22, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29351391/the-bile-acids-deoxycholic-acid-and-ursodeoxycholic-acid-regulate-colonic-epithelial-wound-healing
#15
Magdalena S Mroz, Natalia K Lajczak, Bridie J Goggins, Simon Keely, Stephen Joseph Keely
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although, bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable, supports was assessed over 48 hrs {plus minus} bile acids...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29346429/the-farnesoid-x-receptor-agonist-obeticholic-acid-upregulates-biliary-excretion-of-asymmetric-dimethylarginine-via-mate-1-during-hepatic-ischemia-reperfusion-injury
#16
Andrea Ferrigno, Laura Giuseppina Di Pasqua, Clarissa Berardo, Veronica Siciliano, Vittoria Rizzo, Luciano Adorini, Plinio Richelmi, Mariapia Vairetti
BACKGROUND: We previously showed that increased asymmetric dimethylarginine (ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R), prompting us to study the effects of the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R. MATERIAL AND METHODS: Male Wistar rats were orally administered 10mg/kg/day of OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia or sham-operated...
2018: PloS One
https://www.readbyqxmd.com/read/29339445/bile-acids-in-glucose-metabolism-in-health-and-disease
#17
REVIEW
Hagit Shapiro, Aleksandra A Kolodziejczyk, Daniel Halstuch, Eran Elinav
Bile acids (BAs) are cholesterol-derived metabolites that facilitate the intestinal absorption and transport of dietary lipids. Recently, BAs also emerged as pivotal signaling molecules controlling glucose, lipid, and energy metabolism by binding to the nuclear hormone farnesoid X receptor (FXR) and Takeda G protein receptor 5 (TGR5) in multiple organs, leading to regulation of intestinal incretin secretion, hepatic gluconeogenesis, glycogen synthesis, energy expenditure, inflammation, and gut microbiome configuration...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29328388/gw4064-attenuates-lipopolysaccharide%C3%A2-induced-hepatic-inflammation-and-apoptosis-through-inhibition-of-the-toll%C3%A2-like-receptor-4%C3%A2-mediated-p38-mitogen%C3%A2-activated-protein-kinase-signaling-pathway-in-mice
#18
Hsuan-Miao Liu, Tzung-Yan Lee, Jyh-Fei Liao
Liver injury is associated with devastating consequences caused by inflammation and apoptosis. The farnesoid X receptor (FXR) is a nuclear receptor that has an essential role in hepatoprotection by maintaining the homeostasis of liver metabolism. The present study investigated the capacity of the FXR agonist GW4064 to protect the livers of mice from lipopolysaccharide (LPS)‑induced inflammation and apoptosis. Male C57BL/6J [wild‑type (WT)] and FXR knockout (KO) mice were intraperitoneally injected with LPS or saline...
January 8, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29325602/bile-acid-metabolism-in-liver-pathobiology
#19
John Y L Chiang, Jessica M Ferrell
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism...
January 11, 2018: Gene Expression
https://www.readbyqxmd.com/read/29315013/on-the-evolution-of-bile-salts-and-the-farnesoid-x-receptor-in-vertebrates
#20
Kim Frisch, Aage Kristian Olsen Alstrup
In recent decades, our knowledge of bile salts has undergone a vast development, and bile salts are now known not only for their detergent properties that aid in the absorption of dietary lipids but also for their interaction with specific nuclear and membrane receptors. In particular, it has been realized that the response of the farnesoid X receptor (FXR) to bile acids provides a signal bridge between the liver and small intestine, controlling the intracellular levels, biosynthesis, and enterohepatic circulation of bile acids...
March 2018: Physiological and Biochemical Zoology: PBZ
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