The Experts below are selected from a list of 183 Experts worldwide ranked by ideXlab platform
Shogo Takahashi - One of the best experts on this subject based on the ideXlab platform.
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bile acid sequestration reverses liver injury and prevents progression of nonalcoholic steatohepatitis in western diet fed mice
Journal of Biological Chemistry, 2020Co-Authors: Shogo Takahashi, Suman Ranjit, Andrew E Libby, David J Orlicky, Alexander Dvornikov, Xiaoxin X Wang, Komuraiah Myakala, Bryce A JonesAbstract:: Nonalcoholic fatty liver disease is a rapidly rising problem in the 21st century and is a leading cause of chronic liver disease that can lead to end-stage liver diseases, including cirrhosis and hepatocellular cancer. Despite this rising epidemic, no pharmacological treatment has yet been established to treat this disease. The rapidly increasing prevalence of nonalcoholic fatty liver disease and its aggressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent disease progression. Alterations in microbiome dynamics and dysbiosis play an important role in liver disease and may represent targetable pathways to treat liver disorders. Improving microbiome properties or restoring normal bile acid metabolism may prevent or slow the progression of liver diseases such as NASH. Importantly, aberrant systemic circulation of bile acids can greatly disrupt metabolic homeostasis. Bile acid sequestrants are orally administered polymers that bind bile acids in the intestine, forming nonabsorbable complexes. Bile acid sequestrants interrupt Intestinal Reabsorption of bile acids, decreasing their circulating levels. We determined that treatment with the bile acid sequestrant sevelamer reversed the liver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in a Western diet-induced NASH mouse model. Metabolomics and microbiome analysis revealed that this beneficial effect is associated with changes in the microbiota population and bile acid composition, including reversing microbiota complexity in cecum by increasing Lactobacillus and decreased Desulfovibrio The net effect of these changes was improvement in liver function and markers of liver injury and the positive effects of reversal of insulin resistance.
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Bile acid sequestration reverses liver injury and prevents progression of nonalcoholic steatohepatitis in Western diet–fed mice
The Journal of biological chemistry, 2020Co-Authors: Shogo Takahashi, Suman Ranjit, Andrew E Libby, David J Orlicky, Alexander Dvornikov, Xiaoxin X Wang, Komuraiah Myakala, Yuhuan Luo, Cen Xie, Bryce A JonesAbstract:Nonalcoholic fatty liver disease is a rapidly rising problem in the 21st century and is a leading cause of chronic liver disease that can lead to end-stage liver diseases, including cirrhosis and hepatocellular cancer. Despite this rising epidemic, no pharmacological treatment has yet been established to treat this disease. The rapidly increasing prevalence of nonalcoholic fatty liver disease and its aggressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent disease progression. Alterations in microbiome dynamics and dysbiosis play an important role in liver disease and may represent targetable pathways to treat liver disorders. Improving microbiome properties or restoring normal bile acid metabolism may prevent or slow the progression of liver diseases such as NASH. Importantly, aberrant systemic circulation of bile acids can greatly disrupt metabolic homeostasis. Bile acid sequestrants are orally administered polymers that bind bile acids in the intestine, forming nonabsorbable complexes. Bile acid sequestrants interrupt Intestinal Reabsorption of bile acids, decreasing their circulating levels. We determined that treatment with the bile acid sequestrant sevelamer reversed the liver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in a Western diet-induced NASH mouse model. Metabolomics and microbiome analysis revealed that this beneficial effect is associated with changes in the microbiota population and bile acid composition, including reversing microbiota complexity in cecum by increasing Lactobacillus and decreased Desulfovibrio The net effect of these changes was improvement in liver function and markers of liver injury and the positive effects of reversal of insulin resistance.
Bryce A Jones - One of the best experts on this subject based on the ideXlab platform.
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bile acid sequestration reverses liver injury and prevents progression of nonalcoholic steatohepatitis in western diet fed mice
Journal of Biological Chemistry, 2020Co-Authors: Shogo Takahashi, Suman Ranjit, Andrew E Libby, David J Orlicky, Alexander Dvornikov, Xiaoxin X Wang, Komuraiah Myakala, Bryce A JonesAbstract:: Nonalcoholic fatty liver disease is a rapidly rising problem in the 21st century and is a leading cause of chronic liver disease that can lead to end-stage liver diseases, including cirrhosis and hepatocellular cancer. Despite this rising epidemic, no pharmacological treatment has yet been established to treat this disease. The rapidly increasing prevalence of nonalcoholic fatty liver disease and its aggressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent disease progression. Alterations in microbiome dynamics and dysbiosis play an important role in liver disease and may represent targetable pathways to treat liver disorders. Improving microbiome properties or restoring normal bile acid metabolism may prevent or slow the progression of liver diseases such as NASH. Importantly, aberrant systemic circulation of bile acids can greatly disrupt metabolic homeostasis. Bile acid sequestrants are orally administered polymers that bind bile acids in the intestine, forming nonabsorbable complexes. Bile acid sequestrants interrupt Intestinal Reabsorption of bile acids, decreasing their circulating levels. We determined that treatment with the bile acid sequestrant sevelamer reversed the liver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in a Western diet-induced NASH mouse model. Metabolomics and microbiome analysis revealed that this beneficial effect is associated with changes in the microbiota population and bile acid composition, including reversing microbiota complexity in cecum by increasing Lactobacillus and decreased Desulfovibrio The net effect of these changes was improvement in liver function and markers of liver injury and the positive effects of reversal of insulin resistance.
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Bile acid sequestration reverses liver injury and prevents progression of nonalcoholic steatohepatitis in Western diet–fed mice
The Journal of biological chemistry, 2020Co-Authors: Shogo Takahashi, Suman Ranjit, Andrew E Libby, David J Orlicky, Alexander Dvornikov, Xiaoxin X Wang, Komuraiah Myakala, Yuhuan Luo, Cen Xie, Bryce A JonesAbstract:Nonalcoholic fatty liver disease is a rapidly rising problem in the 21st century and is a leading cause of chronic liver disease that can lead to end-stage liver diseases, including cirrhosis and hepatocellular cancer. Despite this rising epidemic, no pharmacological treatment has yet been established to treat this disease. The rapidly increasing prevalence of nonalcoholic fatty liver disease and its aggressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent disease progression. Alterations in microbiome dynamics and dysbiosis play an important role in liver disease and may represent targetable pathways to treat liver disorders. Improving microbiome properties or restoring normal bile acid metabolism may prevent or slow the progression of liver diseases such as NASH. Importantly, aberrant systemic circulation of bile acids can greatly disrupt metabolic homeostasis. Bile acid sequestrants are orally administered polymers that bind bile acids in the intestine, forming nonabsorbable complexes. Bile acid sequestrants interrupt Intestinal Reabsorption of bile acids, decreasing their circulating levels. We determined that treatment with the bile acid sequestrant sevelamer reversed the liver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in a Western diet-induced NASH mouse model. Metabolomics and microbiome analysis revealed that this beneficial effect is associated with changes in the microbiota population and bile acid composition, including reversing microbiota complexity in cecum by increasing Lactobacillus and decreased Desulfovibrio The net effect of these changes was improvement in liver function and markers of liver injury and the positive effects of reversal of insulin resistance.
Frans Stellaard - One of the best experts on this subject based on the ideXlab platform.
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bile salt sequestration induces hepatic de novo lipogenesis through farnesoid x receptor and liver x receptorα controlled metabolic pathways in mice
Hepatology, 2010Co-Authors: Hilde Herrema, Maxi Meissner, Theo H Van Dijk, Gemma Brufau, Renze Boverhof, Maaike H Oosterveer, Dirkjan Reijngoud, Michael Muller, Frans StellaardAbstract:Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through signaling pathways involving farnesoid X receptor (FXR) and liver X receptor alpha (LXR alpha). We quantitatively assessed kinetic parameters of bile salt metabolism in lean C57Bl/6J and in obese, diabetic db/db mice upon bile salt sequestration using colesevelam HCl (2% wt/wt in diet) and related these to quantitative changes in hepatic lipid metabolism. As expected, bile salt sequestration reduced Intestinal bile salt Reabsorption. Importantly, bile salt pool size and biliary bile salt secretion remained unchanged upon sequestrant treatment due to compensation by de navo bile salt synthesis in both models. Nevertheless, lean and db/db mice showed increased, mainly periportally confined, hepatic TG contents, increased expression of lipogenic genes, and increased fractional contributions of newly synthesized fatty acids. Lipogenic gene expression was not induced in sequestrant-treated Fxr(-/-) and Lxr alpha(-/-) mice compared with wild-type littermates, in fine with reports indicating a regulatory role of FXR and LXR alpha in bile salt-mediated regulation of hepatic lipid metabolism. Conclusion Bile salt sequestration by colesevelam induces the lipogenic pathway in an FXR- and LXR alpha-dependent manner without affecting the total pool size of bile salts in mice. We speculate that a shift from. Intestinal Reabsorption to de novo synthesis as source of bile salts upon bile salt sequestration affects zonation of metabolic processes within the liver acinus. (HEPATOLOGY 2010;51:806-816.)
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Bile salt sequestration induces hepatic de novo lipogenesis through farnesoid X receptor– and liver X receptorα–controlled metabolic pathways in mice
Hepatology (Baltimore Md.), 2010Co-Authors: Hilde Herrema, Frans Stellaard, Maxi Meissner, Theo H Van Dijk, Gemma Brufau, Renze Boverhof, Maaike H Oosterveer, Dirkjan Reijngoud, Michael Muller, Albert K. GroenAbstract:Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through signaling pathways involving farnesoid X receptor (FXR) and liver X receptor alpha (LXR alpha). We quantitatively assessed kinetic parameters of bile salt metabolism in lean C57Bl/6J and in obese, diabetic db/db mice upon bile salt sequestration using colesevelam HCl (2% wt/wt in diet) and related these to quantitative changes in hepatic lipid metabolism. As expected, bile salt sequestration reduced Intestinal bile salt Reabsorption. Importantly, bile salt pool size and biliary bile salt secretion remained unchanged upon sequestrant treatment due to compensation by de navo bile salt synthesis in both models. Nevertheless, lean and db/db mice showed increased, mainly periportally confined, hepatic TG contents, increased expression of lipogenic genes, and increased fractional contributions of newly synthesized fatty acids. Lipogenic gene expression was not induced in sequestrant-treated Fxr(-/-) and Lxr alpha(-/-) mice compared with wild-type littermates, in fine with reports indicating a regulatory role of FXR and LXR alpha in bile salt-mediated regulation of hepatic lipid metabolism. Conclusion Bile salt sequestration by colesevelam induces the lipogenic pathway in an FXR- and LXR alpha-dependent manner without affecting the total pool size of bile salts in mice. We speculate that a shift from. Intestinal Reabsorption to de novo synthesis as source of bile salts upon bile salt sequestration affects zonation of metabolic processes within the liver acinus. (HEPATOLOGY 2010;51:806-816.)
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Cyclosporin A and Enterohepatic Circulation of Bile Salts in Rats: Decreased Cholate Synthesis but Increased Intestinal Reabsorption
The Journal of pharmacology and experimental therapeutics, 2003Co-Authors: Christian V. Hulzebos, Henkjan J. Verkade, Henk Wolters, Torsten Plösch, Werner Kramer, Siegfried Stengelin, Frans Stellaard, Pieter J. J. Sauer, Folkert KuipersAbstract:Cyclosporin A (CsA) has been shown to inhibit synthesis and hepatobiliary transport of bile salts. However, effects of CsA on the enterohepatic circulation of bile salts in vivo are largely unknown. We characterized the effects of CsA on the enterohepatic circulation of cholate, with respect to synthesis rate, pool size, cycling time, Intestinal absorption, and the expression of relevant transporters in liver and intestine in rats. CsA (1 mg · 100 g−1 · day−1 s.c.) or its solvent was administered daily to male rats for 10 days. Cholate synthesis rate and pool size were determined by a 2H4-cholate dilution technique. Bile and feces were collected for determination of cholate and total bile salts, respectively. Cycling time and Intestinal absorption of cholate were calculated. The mRNA levels and corresponding transporter protein levels in liver and intestine were assessed by real-time polymerase chain reaction and Western analysis, respectively. CsA treatment decreased cholate synthesis rate by 71%, but did not affect pool size or cycling time. CsA reduced the amount of cholate lost per enterohepatic cycle by ∼70%. Protein levels of the apical sodium-dependent bile salt transporter (Asbt) were 2-fold increased in distal ileum of CsA-treated rats, due to post-transcriptional events. In conclusion, chronic CsA treatment markedly reduces cholate synthesis rate in rats, but does not affect cholate pool size or cycling time. Our results strongly suggest that CsA enhances efficacy of Intestinal cholate Reabsorption through increased Asbt protein expression in the distal ileum, which contributes to maintenance of cholate pool size in CsA-treated rats.
Hilde Herrema - One of the best experts on this subject based on the ideXlab platform.
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bile salt sequestration induces hepatic de novo lipogenesis through farnesoid x receptor and liver x receptorα controlled metabolic pathways in mice
Hepatology, 2010Co-Authors: Hilde Herrema, Maxi Meissner, Theo H Van Dijk, Gemma Brufau, Renze Boverhof, Maaike H Oosterveer, Dirkjan Reijngoud, Michael Muller, Frans StellaardAbstract:Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through signaling pathways involving farnesoid X receptor (FXR) and liver X receptor alpha (LXR alpha). We quantitatively assessed kinetic parameters of bile salt metabolism in lean C57Bl/6J and in obese, diabetic db/db mice upon bile salt sequestration using colesevelam HCl (2% wt/wt in diet) and related these to quantitative changes in hepatic lipid metabolism. As expected, bile salt sequestration reduced Intestinal bile salt Reabsorption. Importantly, bile salt pool size and biliary bile salt secretion remained unchanged upon sequestrant treatment due to compensation by de navo bile salt synthesis in both models. Nevertheless, lean and db/db mice showed increased, mainly periportally confined, hepatic TG contents, increased expression of lipogenic genes, and increased fractional contributions of newly synthesized fatty acids. Lipogenic gene expression was not induced in sequestrant-treated Fxr(-/-) and Lxr alpha(-/-) mice compared with wild-type littermates, in fine with reports indicating a regulatory role of FXR and LXR alpha in bile salt-mediated regulation of hepatic lipid metabolism. Conclusion Bile salt sequestration by colesevelam induces the lipogenic pathway in an FXR- and LXR alpha-dependent manner without affecting the total pool size of bile salts in mice. We speculate that a shift from. Intestinal Reabsorption to de novo synthesis as source of bile salts upon bile salt sequestration affects zonation of metabolic processes within the liver acinus. (HEPATOLOGY 2010;51:806-816.)
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Bile salt sequestration induces hepatic de novo lipogenesis through farnesoid X receptor– and liver X receptorα–controlled metabolic pathways in mice
Hepatology (Baltimore Md.), 2010Co-Authors: Hilde Herrema, Frans Stellaard, Maxi Meissner, Theo H Van Dijk, Gemma Brufau, Renze Boverhof, Maaike H Oosterveer, Dirkjan Reijngoud, Michael Muller, Albert K. GroenAbstract:Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through signaling pathways involving farnesoid X receptor (FXR) and liver X receptor alpha (LXR alpha). We quantitatively assessed kinetic parameters of bile salt metabolism in lean C57Bl/6J and in obese, diabetic db/db mice upon bile salt sequestration using colesevelam HCl (2% wt/wt in diet) and related these to quantitative changes in hepatic lipid metabolism. As expected, bile salt sequestration reduced Intestinal bile salt Reabsorption. Importantly, bile salt pool size and biliary bile salt secretion remained unchanged upon sequestrant treatment due to compensation by de navo bile salt synthesis in both models. Nevertheless, lean and db/db mice showed increased, mainly periportally confined, hepatic TG contents, increased expression of lipogenic genes, and increased fractional contributions of newly synthesized fatty acids. Lipogenic gene expression was not induced in sequestrant-treated Fxr(-/-) and Lxr alpha(-/-) mice compared with wild-type littermates, in fine with reports indicating a regulatory role of FXR and LXR alpha in bile salt-mediated regulation of hepatic lipid metabolism. Conclusion Bile salt sequestration by colesevelam induces the lipogenic pathway in an FXR- and LXR alpha-dependent manner without affecting the total pool size of bile salts in mice. We speculate that a shift from. Intestinal Reabsorption to de novo synthesis as source of bile salts upon bile salt sequestration affects zonation of metabolic processes within the liver acinus. (HEPATOLOGY 2010;51:806-816.)
Suman Ranjit - One of the best experts on this subject based on the ideXlab platform.
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bile acid sequestration reverses liver injury and prevents progression of nonalcoholic steatohepatitis in western diet fed mice
Journal of Biological Chemistry, 2020Co-Authors: Shogo Takahashi, Suman Ranjit, Andrew E Libby, David J Orlicky, Alexander Dvornikov, Xiaoxin X Wang, Komuraiah Myakala, Bryce A JonesAbstract:: Nonalcoholic fatty liver disease is a rapidly rising problem in the 21st century and is a leading cause of chronic liver disease that can lead to end-stage liver diseases, including cirrhosis and hepatocellular cancer. Despite this rising epidemic, no pharmacological treatment has yet been established to treat this disease. The rapidly increasing prevalence of nonalcoholic fatty liver disease and its aggressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent disease progression. Alterations in microbiome dynamics and dysbiosis play an important role in liver disease and may represent targetable pathways to treat liver disorders. Improving microbiome properties or restoring normal bile acid metabolism may prevent or slow the progression of liver diseases such as NASH. Importantly, aberrant systemic circulation of bile acids can greatly disrupt metabolic homeostasis. Bile acid sequestrants are orally administered polymers that bind bile acids in the intestine, forming nonabsorbable complexes. Bile acid sequestrants interrupt Intestinal Reabsorption of bile acids, decreasing their circulating levels. We determined that treatment with the bile acid sequestrant sevelamer reversed the liver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in a Western diet-induced NASH mouse model. Metabolomics and microbiome analysis revealed that this beneficial effect is associated with changes in the microbiota population and bile acid composition, including reversing microbiota complexity in cecum by increasing Lactobacillus and decreased Desulfovibrio The net effect of these changes was improvement in liver function and markers of liver injury and the positive effects of reversal of insulin resistance.
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Bile acid sequestration reverses liver injury and prevents progression of nonalcoholic steatohepatitis in Western diet–fed mice
The Journal of biological chemistry, 2020Co-Authors: Shogo Takahashi, Suman Ranjit, Andrew E Libby, David J Orlicky, Alexander Dvornikov, Xiaoxin X Wang, Komuraiah Myakala, Yuhuan Luo, Cen Xie, Bryce A JonesAbstract:Nonalcoholic fatty liver disease is a rapidly rising problem in the 21st century and is a leading cause of chronic liver disease that can lead to end-stage liver diseases, including cirrhosis and hepatocellular cancer. Despite this rising epidemic, no pharmacological treatment has yet been established to treat this disease. The rapidly increasing prevalence of nonalcoholic fatty liver disease and its aggressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent disease progression. Alterations in microbiome dynamics and dysbiosis play an important role in liver disease and may represent targetable pathways to treat liver disorders. Improving microbiome properties or restoring normal bile acid metabolism may prevent or slow the progression of liver diseases such as NASH. Importantly, aberrant systemic circulation of bile acids can greatly disrupt metabolic homeostasis. Bile acid sequestrants are orally administered polymers that bind bile acids in the intestine, forming nonabsorbable complexes. Bile acid sequestrants interrupt Intestinal Reabsorption of bile acids, decreasing their circulating levels. We determined that treatment with the bile acid sequestrant sevelamer reversed the liver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in a Western diet-induced NASH mouse model. Metabolomics and microbiome analysis revealed that this beneficial effect is associated with changes in the microbiota population and bile acid composition, including reversing microbiota complexity in cecum by increasing Lactobacillus and decreased Desulfovibrio The net effect of these changes was improvement in liver function and markers of liver injury and the positive effects of reversal of insulin resistance.
