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Farnesoid x receptor

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https://www.readbyqxmd.com/read/29351391/the-bile-acids-deoxycholic-acid-and-ursodeoxycholic-acid-regulate-colonic-epithelial-wound-healing
#1
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
#2
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/29344511/crosstalk-of-hyperglycemia-and-dyslipidemia-in-diabetic-kidney-disease
#3
REVIEW
Wen Su, Rong Cao, Yong Cheng He, You Fei Guan, Xiong Zhong Ruan
Background: Diabetic kidney disease (DKD) is defined by the functional, structural, and clinical abnormalities of the kidney that are caused by diabetes. Summary: One-third of both type 1 diabetes and type 2 diabetes patients suffer from DKD, which is the leading cause of end-stage renal disease, and is also associated with cardiovascular disease and high public health care costs. Serum glucose level and lipid level are key factors in the pathogenesis of DKD and are modifiable...
December 2017: Kidney Diseases
https://www.readbyqxmd.com/read/29339445/bile-acids-in-glucose-metabolism-in-health-and-disease
#4
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/29330189/targeted-synthesis-and-characterization-of-a-gene-cluster-encoding-nad-p-h-dependent-3%C3%AE-3%C3%AE-and-12%C3%AE-hydroxysteroid-dehydrogenases-from-eggerthella-cag-298-a-gut-metagenomic-sequence
#5
Sean M Mythen, Saravanan Devendran, Celia Méndez-García, Isaac Cann, Jason M Ridlon
Gut metagenomic sequences provide a rich source of microbial genes, the majority of which are annotated by homology or unknown. Genes and gene pathways that encode enzymes catalyzing biotransformation of host bile acids are important to identify in gut metagenomic sequences due to the importance of bile acids on gut microbiome structure and host physiology. Hydroxysteroid dehydrogenases (HSDH) are pyridine nucleotide-dependent enzymes with stereo-specificity and regio-specificity for bile acid and steroid hydroxyl groups...
January 12, 2018: Applied and Environmental Microbiology
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
#6
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
#7
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/29325272/-advances-in-the-treatment-of-primary-biliary-cholangitis
#8
Y M Li, Q X Wang, X Ma
Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving intrahepatic interlobular bile ducts and can progress to liver fibrosis, liver cirrhosis, and even liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapeutic drug for PBC and can delay disease progression, but as high as 40% of patients have suboptimal response to UDCA. Obeticholic acid, a farnesoid X receptor agonist, has been approved by FDA in May 2016 for patients who have no response to UDCA treatment or cannot tolerate such treatment...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29315013/on-the-evolution-of-bile-salts-and-the-farnesoid-x-receptor-in-vertebrates
#9
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
https://www.readbyqxmd.com/read/29297503/cholecystectomy-a-way-forward-and-back-to-metabolic-syndrome
#10
EDITORIAL
Gabriella Garruti, David Q-H Wang, Agostino Di Ciaula, Piero Portincasa
The gallbladder provides rhythmic secretion of concentrated bile acids (BAs) during fasting and postprandially contributes to digestion of dietary lipids. In addition, BAs activate metabolic pathways governing gluco-lipid homeostasis and energy expenditure via the farnesoid X nuclear receptor (FXR), G protein-coupled BA receptor 1 (GPBAR-1), and fibroblast growth factor 19 (FGF19) in the liver, intestine, brown fat, and muscle. Cholecystectomy is standard treatment worldwide for symptomatic gallstone patients...
January 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29286073/proteasome-inhibition-protects-against-diet-induced-gallstone-formation-through-modulation-of-cholesterol-and-bile-acid-homeostasis
#11
Eun-Ji Lee, Min Hee Kim, Ye-Ryung Kim, Joo-Won Park, Woo-Jae Park
Gallstone disease is one of the most prevalent and costly gastrointestinal disorders worldwide. Gallstones are formed in the biliary system by cholesterol secretions in bile, which result from excess cholesterol, a deficiency in bile salts or a combination of the two. The present study examined the effects of proteasome inhibition on gallstone formation using the proteasome inhibitors bortezomib (BT) and carfilzomib (CF). C57BL/6J mice were fed a lithogenic diet to generate gallstones and injected with BT or CF for 12 weeks...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29283075/evaluation-of-farnesoid-x-receptor-target-gene-induction-in-human-hepatocytes-amino-acid-conjugation
#12
Jean Simmermacher, Michael Sinz
BACKGROUND: The nuclear hormone receptor, farnesoid X receptor (FXR) regulates the transcription of genes associated with bile acid metabolism and disposition. OBJECTIVE: This study investigates possible changes in the expression of target genes responsible for amino acid conjugation, i.e., bile acid-CoA synthetase (BACS) and bile acid-CoA: amino acid N-acetyltransferase (BAT). These genes have been shown to be inducible by FXR agonists in rat models, however, to date no studies have been conducted in a human hepatocyte model...
December 27, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29280057/effects-of-sleeve-gastrectomy-on-nonalcoholic-fatty-liver-disease-in-an-obese-rat-model
#13
Kiminori Watanabe, Masayuki Ohta, Hiroomi Takayama, Kazuhiro Tada, Yuki Shitomi, Takahide Kawasaki, Yuichiro Kawano, Yuichi Endo, Yukio Iwashita, Masafumi Inomata
BACKGROUND/AIM: Laparoscopic sleeve gastrectomy (SG) is an increasingly used bariatric surgery, which is reported to be effective for nonalcoholic fatty liver disease (NAFLD). Recently, activation of farnesoid X receptor (FXR), which is a nuclear receptor of bile acid (BA), was reported to contribute to the resolution of NAFLD. However, it is unclear whether SG has an effect on expression of FXR in the liver. We aimed to investigate the expression of FXR and its related factors in the liver after SG and to clarify the relationship between changes in FXR expression and NAFLD in an obese rat model...
December 26, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29275233/synthesis-physicochemical-properties-and-biological-activity-of-bile-acids-3-glucuronides-novel-insights-into-bile-acid-signalling-and-detoxification
#14
Serena Mostarda, Daniela Passeri, Andrea Carotti, Bruno Cerra, Carolina Colliva, Tiziana Benicchi, Antonio Macchiarulo, Roberto Pellicciari, Antimo Gioiello
Glucuronidation is considered an important detoxification pathway of bile acids especially in cholestatic conditions. Glucuronides are less toxic than the parent free forms and are more easily excreted in urine. However, the pathophysiological significance of bile acid glucuronidation is still controversial and debated among the scientific community. Progress in this field has been strongly limited by the lack of appropriate methods for the preparation of pure glucuronides in the amount needed for biological and pharmacological studies...
December 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29259959/fexaramine-inhibits-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-ligand-induced-osteoclast-formation-via-nuclear-factor-of-activated-t-cells-signaling-pathways
#15
Ting Zheng, Na-Young Kim, Mijung Yim
Background: Osteoclasts are bone resorbing cells and are responsible for bone erosion in diseases as diverse as osteoporosis, periodontitis, and rheumatoid arthritis. Fexaramine has been developed as an agonist for the farnesoid X receptor (FXR). This study investigated the effects of fexaramine on receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast formation and signaling pathways. Methods: Osteoclasts were formed by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL...
November 2017: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/29259742/synthesis-and-biological-evaluation-of-a-series-of-bile-acid-derivatives-as-fxr-agonists-for-treatment-of-nash
#16
Hualing Xiao, Peng Li, Xiaolin Li, Haiying He, Jianhua Wang, Fengxun Guo, Jiliang Zhang, Luxia Wei, Hongmei Zhang, Yueyuan Shi, Lijuan Hou, Liang Shen, Zhengxia Chen, Chunyan Du, Shouliang Fu, Pengtao Zhang, Fei Hao, Ping Wang, Deming Xu, Wei Liang, Xin Tian, Aiming Zhang, Xingdong Cheng, Ling Yang, Xiangjian Wang, Xiquan Zhang, Jian Li, Shuhui Chen
Farnesoid X receptor (FXR) has become a particularly attractive target for the discovery of drugs for the treatment of liver and metabolic diseases. Obeticholic acid (INT-747), a FXR agonist, has advanced into clinical phase III trials in patients with nonalcoholic steatohepatitis (NASH), but adverse effects (e.g., pruritus, LDL increase) were observed. Pruritus might be induced by Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1), and there are chances to develop FXR agonists with higher selectivity over TGR5...
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29247356/current-and-future-pharmacological-therapies-for-nafld-nash
#17
REVIEW
Yoshio Sumida, Masashi Yoneda
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation...
December 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29241453/bile-acid-is-a-significant-host-factor-shaping-the-gut-microbiome-of-diet-induced-obese-mice
#18
Xiaojiao Zheng, Fengjie Huang, Aihua Zhao, Sha Lei, Yunjing Zhang, Guoxiang Xie, Tianlu Chen, Chun Qu, Cynthia Rajani, Bing Dong, Defa Li, Wei Jia
BACKGROUND: Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way. RESULTS: We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites...
December 14, 2017: BMC Biology
https://www.readbyqxmd.com/read/29235094/effects-of-corilagin-on-alleviating-cholestasis-via-fxr-associated-pathways-in-vitro-and-in-vivo
#19
Fan Yang, Yao Wang, Gang Li, Juan Xue, Zhi-Lin Chen, Feng Jin, Lei Luo, Xuan Zhou, Qian Ma, Xin Cai, Hua-Rong Li, Lei Zhao
BACKGROUND AND PURPOSE: This aim of this study was to investigate the effects of corilagin on alleviating intrahepatic cholestasis by regulating liver FXR (farnesoid X receptor)-associated pathways in vitro and in vivo. EXPERIMENTAL APPROACH: Cellular and animal models were treated with different concentrations of corilagin. In the cellular experiments, FXR expression was up-regulated by either lentiviral transduction or GW4064 treatment and down-regulated by either siRNA technology or treatment with guggulsterones...
December 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29235014/increased-bile-acid-signals-after-duodenal-jejunal-bypass-improve-non-alcoholic-steatohepatitis-nash-in-a-rodent-model-of-diet-induced-nash
#20
Takahiro Tsuchiya, Takeshi Naitoh, Munenori Nagao, Naoki Tanaka, Kazuhiro Watanabe, Hirofumi Imoto, Tomohiro Miyachi, Fuyuhiko Motoi, Michiaki Unno
BACKGROUND: The increasing incidence of non-alcoholic steatohepatitis (NASH) has resulted in it becoming a common cause of liver-related mortality; however, no efficient treatment has been established. It has been reported that bariatric surgery improves metabolic comorbidities, such as diabetes mellitus and NASH. Although the mechanism is unclear, it is thought that the changes in bile acid (BA) signaling via its nuclear receptor, farnesoid X receptor (FXR), produce various metabolic effects...
December 12, 2017: Obesity Surgery
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