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https://www.readbyqxmd.com/read/28338522/developments-in-intestinal-cholesterol-transport-and-triglyceride-absorption
#1
Yared Paalvast, Jan Freark de Boer, Albert K Groen
PURPOSE OF REVIEW: To discuss recent advances in research focused on intestinal lipid handling. RECENT FINDINGS: An important strategy in reducing atherosclerosis and risk of cardiovascular events is to increase the rate of reverse cholesterol transport, including its final step; cholesterol excretion from the body. The rate of removal is determined by a complex interplay between the factors involved in regulation of intestinal cholesterol absorption. One of these factors is a process known as transintestinal cholesterol excretion...
March 23, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28333693/pediatric-intestinal-failure-associated-liver-disease
#2
Cathleen M Courtney, Brad W Warner
PURPOSE OF REVIEW: The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients. RECENT FINDINGS: Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively...
March 22, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28324023/long-chain-free-fatty-acid-receptor-gpr120-mediates-oil-induced-gip-secretion-through-cck-in-male-mice
#3
Akiko Sankoda, Norio Harada, Kanako Iwasaki, Shunsuke Yamane, Yuki Murata, Kimitaka Shibue, Yotsapon Thewjitcharoen, Kazuyo Suzuki, Takanari Harada, Yoshinori Kanemaru, Satoko Shimazu-Kuwahara, Akira Hirasawa, Nobuya Inagaki
Free fatty acid receptors GPR120 and GPR40 are involved in the secretion of gut hormones. GPR120 and GPR40 are expressed in enteroendocrine K-cells and their activation induces the secretion of the incretin glucose-dependent insulinotropic polypeptide (GIP). However, the role of these receptors in fat-induced GIP secretion in vivo and the associated mechanisms are unclear. In this study, we investigated corn oil-induced GIP secretion in GPR120-knockout (GPR120-/-) and GPR40-knockout (GPR40-/-) mice. Oil-induced GIP secretion was reduced by 50% and 80% in GPR120-/- and GPR40-/- mice compared to that in wild-type (WT) mice, respectively...
March 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28315136/ursodeoxycholic-acid-suppresses-lipogenesis-in-mouse-liver-possible-role-of-the-decrease-in-%C3%AE-muricholic-acid-a-farnesoid-x-receptor-antagonist
#4
Kyosuke Fujita, Yusuke Iguchi, Mizuho Une, Shiro Watanabe
The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR...
March 17, 2017: Lipids
https://www.readbyqxmd.com/read/28304141/evidence-connecting-old-new-and-neglected-glucose-lowering-drugs-to-bile-acid-induced-glp-1-secretion-a-review
#5
REVIEW
Martin L Kårhus, Andreas Brønden, David P Sonne, Tina Vilsbøll, Fillip K Knop
Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor (FXR), in intestinal L cell...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28302491/bile-acids-and-their-receptors-during-liver-regeneration-dangerous-protectors
#6
REVIEW
Grégory Merlen, José Ursic-Bedoya, Valeska Jourdainne, Nicolas Kahale, Mathilde Glenisson, Isabelle Doignon, Dominique Rainteau, Thierry Tordjmann
Tissue repair is orchestrated by a finely tuned interplay between processes of regeneration, inflammation and cell protection, allowing organisms to restore their integrity after partial loss of cells or organs. An important, although largely unexplored feature is that after injury and during liver repair, liver functions have to be maintained to fulfill the peripheral demand. This is particularly critical for bile secretion, which has to be finely modulated in order to preserve liver parenchyma from bile-induced injury...
March 23, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28287408/nutrient-sensing-nuclear-receptors-ppar%C3%AE-and-fxr-control-liver-energy-balance
#7
Geoffrey A Preidis, Kang Ho Kim, David D Moore
The nuclear receptors PPARα (encoded by NR1C1) and farnesoid X receptor (FXR, encoded by NR1H4) are activated in the liver in the fasted and fed state, respectively. PPARα activation induces fatty acid oxidation, while FXR controls bile acid homeostasis, but both nuclear receptors also regulate numerous other metabolic pathways relevant to liver energy balance. Here we review evidence that they function coordinately to control key nutrient pathways, including fatty acid oxidation and gluconeogenesis in the fasted state and lipogenesis and glycolysis in the fed state...
March 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28267333/transcriptional-regulation-of-human-udp-glucuronosyltransferase-2b10-by-farnesoid-x-receptor-in-human-hepatoma-hepg2-cells
#8
Danyi Lu, Shuai Wang, Qian Xie, Lianxia Guo, Baojian Wu
Little is known about transcriptional regulators of UDP-glucuronosyltransferase 2B10 (UGT2B10), an enzyme known to glucuronidate many chemicals and drugs such as nicotine and tricyclic antidepressants. Here, we uncovered that UGT2B10 was transcriptionally regulated by farnesoid X receptor (FXR), the bile acid sensing nuclear receptor. GW4064 and chenodeoxycholic acid (two specific FXR agonists) treatment of HepG2 cells led to a significant increase in the mRNA level of UGT2B10. The treated cells also showed enhanced glucuronidation activities toward amitriptyline (an UGT2B10 probe substrate)...
March 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28249296/regulation-of-liver-energy-balance-by-the-nuclear-receptors-farnesoid-x-receptor-and-peroxisome-proliferator-activated-receptor-%C3%AE
#9
Kang Ho Kim, David D Moore
BACKGROUND: The liver undergoes major changes in substrate utilization and metabolic output over the daily feeding and fasting cycle. These changes occur acutely in response to hormones such as insulin and glucagon, with rapid changes in signaling pathways mediated by protein phosphorylation and other post-translational modifications. They are also reflected in chronic alterations in gene expression in response to nutrient-sensitive transcription factors. Among these, the nuclear receptors farnesoid X receptor (FXR) and peroxisome proliferator activated receptor α (PPARα) provide an intriguing, coordinated response to maintain energy balance in the liver...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249291/bile-acid-uptake-transporters-as-targets-for-therapy
#10
Davor Slijepcevic, Stan F J van de Graaf
Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249284/disease-associated-changes-in-bile-acid-profiles-and-links-to-altered-gut-microbiota
#11
Susan A Joyce, Cormac G M Gahan
The gastrointestinal microbiota plays a central role in the host metabolism of bile acids through deconjugation and dehydroxylation reactions, which generate unconjugated free bile acids and secondary bile acids respectively. These microbially generated bile acids are particularly potent signalling molecules that interact with host bile acid receptors (including the farnesoid X receptor, vitamin D receptor and TGR5 receptor) to trigger cellular responses that play essential roles in host lipid metabolism, electrolyte transport and immune regulation...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249279/farnesoid-x-receptor-an-emerging-target-to-combat-obesity
#12
C Daniel De Magalhaes Filho, Michael Downes, Ronald M Evans
Obesity and its associated diseases, including type 2 diabetes, have reached epidemic levels worldwide. However, available treatment options are limited and ineffective in managing the disease. There is therefore an urgent need for the development of new pharmacological solutions. The bile acid (BA) Farnesoid X receptor (FXR) has recently emerged as an attractive candidate. Initially described for their role in lipid and vitamin absorption from diet, BAs are hormones with powerful effects on whole body lipid and glucose metabolism...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249278/mechanisms-of-tauroursodeoxycholate-mediated-hepatoprotection
#13
Dieter Häussinger, Claus Kordes
Ursodeoxycholate and its taurine conjugate tauroursodeoxycholate (TUDC) promote choleresis by triggering the insertion of transport proteins for bile acids into the canalicular and basolateral membranes of hepatocytes. In addition, TUDC exerts hepatoprotective and anti-apoptotic effects, can counteract the action of toxic bile acids and reduce endoplasmic reticulum stress. TUDC can also initiate the differentiation of multipotent mesenchymal stem cells (MSC) including hepatic stellate cells and promote their development into hepatocyte-like cells...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249275/intestinal-farnesoid-x-receptor-signaling-modulates-metabolic-disease
#14
Frank J Gonzalez, Changtao Jiang, Cen Xie, Andrew D Patterson
Farnesoid X receptor (FXR) regulates the synthesis, transport and enterohepatic circulation of bile acids (BA) by modulating the expression of related genes in the liver and small intestine. The composition of the gut microbiota is correlated with metabolic diseases, notably obesity and non-alcoholic fatty acid disease (NAFLD). Recent studies revealed that bacterial metabolism of BA can modulate FXR signaling in the intestine by altering the composition and concentrations of FXR agonist and antagonist. FXR agonist enhances while FXR antagonist suppresses obesity, NAFLD and insulin resistance...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249273/intestinal-farnesoid-x-receptor-and-takeda-g-protein-couple-receptor-5-signaling-in-metabolic-regulation
#15
John Y L Chiang, Preeti Pathak, Hailiang Liu, Ajay Donepudi, Jessica Ferrell, Shannon Boehme
Bile acids play a critical role in the regulation of glucose, lipid and energy metabolisms by activating the nuclear bile acid receptor farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (aka takeda G protein couple receptor 5, TGR5) signaling. Paradoxical roles of FXR in the regulation of glucose and lipid metabolism and metabolic disorder have been reported recently. The activation or inhibition of intestinal FXR signaling has been shown to improve insulin and glucose sensitivity and energy metabolism to prevent diabetes, obesity and non-alcoholic fatty liver disease (NAFLD)...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249269/roles-of-ileal-asbt-and-ost%C3%AE-ost%C3%AE-in-regulating-bile-acid-signaling
#16
Paul A Dawson
BACKGROUND: In addition to their classical role as detergents, bile acids function as signaling molecules to regulate gastrointestinal physiology, carbohydrate and lipid metabolism, and energy expenditure. The pharmacodynamic potential of bile acids is dependent in part on the tight pharmacokinetic control of their concentration and metabolism, properties governed by their hepatic synthesis, enterohepatic cycling, and biotransformation via host and gut microbiota-catalyzed pathways. Key Messages: By altering the normal cycling and compartmentalization of bile acids, changes in hepatobiliary or intestinal transport can affect signaling and lead to the retention of cytotoxic hydrophobic bile acids and cell injury...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249261/crosstalk-between-bile-acids-and-gut-microbiota-and-its-impact-on-farnesoid-x-receptor-signalling
#17
Annika Wahlström, Petia Kovatcheva-Datchary, Marcus Ståhlman, Fredrik Bäckhed, Hanns-Ulrich Marschall
BACKGROUND: The gut microbiota has a substantial impact on health and disease. The human gut microbiota influences the development and progression of metabolic diseases; however, the underlying mechanisms are not fully understood. The nuclear farnesoid X receptor (FXR), which regulates bile acid homeostasis and glucose and lipid metabolism, is activated by primary human and murine bile acids, chenodeoxycholic acid and cholic acid, while rodent specific primary bile acids tauromuricholic acids antagonise FXR activation...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28235703/synthesis-and-biological-evaluations-of-chalcones-flavones-and-chromenes-as-farnesoid-x-receptor-fxr-antagonists
#18
Guoning Zhang, Shuainan Liu, Wenjuan Tan, Ruchi Verma, Yuan Chen, Deyang Sun, Yi Huan, Qian Jiang, Xing Wang, Na Wang, Yang Xu, Chiwai Wong, Zhufang Shen, Ruitang Deng, Jinsong Liu, Yanqiao Zhang, Weishuo Fang
Farnesoid X receptor (FXR), a nuclear receptor mainly distributed in liver and intestine, has been regarded as a potential target for the treatment of various metabolic diseases, cancer and infectious diseases related to liver. Starting from two previously identified chalcone-based FXR antagonists, we tried to increase the activity through the design and synthesis of a library containing chalcones, flavones and chromenes, based on substitution manipulation and conformation (ring closure) restriction strategy...
March 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28223344/an-intestinal-farnesoid-x-receptor-ceramide-signaling-axis-modulates-hepatic-gluconeogenesis-in-mice
#19
Cen Xie, Changtao Jiang, Jingmin Shi, Xiaoxia Gao, Dongxue Sun, Lulu Sun, Ting Wang, Shogo Takahashi, Mallappa Anitha, Kristopher W Krausz, Andrew D Patterson, Frank J Gonzalez
Increasing evidence supports the view that intestinal farnesoid X receptor (FXR) is involved in glucose tolerance and that FXR signaling can be profoundly impacted by the gut microbiota. Selective manipulation of the gut microbiota-FXR signaling axis was reported to significantly impact glucose intolerance, but the precise molecular mechanism remains largely unknown. Here, caffeic acid phenethyl ester (CAPE), an over-the-counter dietary supplement and an inhibitor of bacterial bile salt hydrolase, increased levels of intestinal tauro-β-muricholic acid, which selectively suppresses intestinal FXR signaling...
March 2017: Diabetes
https://www.readbyqxmd.com/read/28222247/bile-acids-and-cardiovascular-function-in-cirrhosis
#20
Andrei Voiosu, Signe Wiese, Theodor Voiosu, Flemming Bendtsen, Søren Møller
Cirrhotic cardiomyopathy and the hyperdynamic syndrome are clinically important complications of cirrhosis but their exact pathogenesis is still partly unknown. Experimental models have proven the cardiotoxic effects of bile acidsand recent studies of their varied receptor-mediated functions offer new insight into their involvement in cardiovascular dysfunction in cirrhosis. Bile acid receptors such as farnesoid X-activated receptor and TGR5 are currently under investigation as potential therapeutic targets in a variety of pathological conditions...
February 21, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
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