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Bile Acid Metabolism
The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
Thomas Q De Aguiar Vallim – 1st expert on this subject based on the ideXlab platform
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rna binding protein zfp36l1 maintains posttranscriptional regulation of Bile Acid Metabolism
Journal of Clinical Investigation, 2017Co-Authors: Elizabeth J Tarling, Bethan L Clifford, Joan Cheng, Pauline Morand, Angela Cheng, Ellen Lester, Tamer Sallam, Martin R Turner, Thomas Q De Aguiar VallimAbstract:: Bile Acids function not only as detergents that facilitate lipid absorption but also as signaling molecules that activate the nuclear receptor farnesoid X receptor (FXR). FXR agonists are currently being evaluated as therapeutic agents for a number of hepatic diseases due to their lipid-lowering and antiinflammatory properties. FXR is also essential for maintaining Bile Acid homeostasis and prevents the accumulation of Bile Acids. Elevated Bile Acids activate FXR, which in turn switches off Bile Acid synthesis by reducing the mRNA levels of Bile Acid synthesis genes, including cholesterol 7α-hydroxylase (Cyp7a1). Here, we show that FXR activation triggers a rapid posttranscriptional mechanism to degrade Cyp7a1 mRNA. We identified the RNA-binding protein Zfp36l1 as an FXR target gene and determined that gain and loss of function of ZFP36L1 reciprocally regulate Cyp7a1 mRNA and Bile Acid levels in vivo. Moreover, we found that mice lacking hepatic ZFP36L1 were protected from diet-induced obesity and steatosis. The reduced adiposity and antisteatotic effects observed in ZFP36L1-deficient mice were accompanied by impaired lipid absorption that was consistent with altered Bile Acid Metabolism. Thus, the ZFP36L1-dependent regulation of Bile Acid Metabolism is an important metabolic contributor to obesity and hepatosteatosis.
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abstract 402 post transcriptional regulation of Bile Acid Metabolism by the rna binding protein zfp36l1
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Elizabeth J Tarling, Bethan L Clifford, Joan Cheng, Pauline Morand, Angela Cheng, Tamer Sallam, Martin R Turner, Thomas Q De Aguiar VallimAbstract:Bile Acids are detergents and important signaling molecules that activate the nuclear receptor FXR to control key metabolic processes, including feedback mechanisms to maintain Bile Acid homeostasis. Activation of FXR decreases the mRNA levels of several Bile Acid synthetic genes, including the rate-limiting enzyme Cyp7a1 . Here we show that Cyp7a1 mRNA levels are very rapidly reduced following FXR activation, indicative of a post-transcriptional mechanism. We identify the RNA binding protein Zfp36l1 as an FXR target gene and show that hepatic overexpression of ZFP36L1 in mice decreases Cyp7a1 mRNA levels. In contrast, Zfp36l1 L -KO mice have increased levels of Cyp7a1 mRNA and biliary Bile Acids as well as reduced plasma cholesterol levels. Zfp36l1 L -KO mice fed a Western diet have reduced diet-induced obesity and steatosis, likely due to impaired lipid absorption, consistent with increased Cyp7a1 levels. Thus, the ZFP36L1-dependent regulation of Bile Acid Metabolism is an important metabolic contributor of dyslipidemia, obesity and hepatosteatosis.
Elizabeth J Tarling – 2nd expert on this subject based on the ideXlab platform
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rna binding protein zfp36l1 maintains posttranscriptional regulation of Bile Acid Metabolism
Journal of Clinical Investigation, 2017Co-Authors: Elizabeth J Tarling, Bethan L Clifford, Joan Cheng, Pauline Morand, Angela Cheng, Ellen Lester, Tamer Sallam, Martin R Turner, Thomas Q De Aguiar VallimAbstract:: Bile Acids function not only as detergents that facilitate lipid absorption but also as signaling molecules that activate the nuclear receptor farnesoid X receptor (FXR). FXR agonists are currently being evaluated as therapeutic agents for a number of hepatic diseases due to their lipid-lowering and antiinflammatory properties. FXR is also essential for maintaining Bile Acid homeostasis and prevents the accumulation of Bile Acids. Elevated Bile Acids activate FXR, which in turn switches off Bile Acid synthesis by reducing the mRNA levels of Bile Acid synthesis genes, including cholesterol 7α-hydroxylase (Cyp7a1). Here, we show that FXR activation triggers a rapid posttranscriptional mechanism to degrade Cyp7a1 mRNA. We identified the RNA-binding protein Zfp36l1 as an FXR target gene and determined that gain and loss of function of ZFP36L1 reciprocally regulate Cyp7a1 mRNA and Bile Acid levels in vivo. Moreover, we found that mice lacking hepatic ZFP36L1 were protected from diet-induced obesity and steatosis. The reduced adiposity and antisteatotic effects observed in ZFP36L1-deficient mice were accompanied by impaired lipid absorption that was consistent with altered Bile Acid Metabolism. Thus, the ZFP36L1-dependent regulation of Bile Acid Metabolism is an important metabolic contributor to obesity and hepatosteatosis.
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abstract 402 post transcriptional regulation of Bile Acid Metabolism by the rna binding protein zfp36l1
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Elizabeth J Tarling, Bethan L Clifford, Joan Cheng, Pauline Morand, Angela Cheng, Tamer Sallam, Martin R Turner, Thomas Q De Aguiar VallimAbstract:Bile Acids are detergents and important signaling molecules that activate the nuclear receptor FXR to control key metabolic processes, including feedback mechanisms to maintain Bile Acid homeostasis. Activation of FXR decreases the mRNA levels of several Bile Acid synthetic genes, including the rate-limiting enzyme Cyp7a1 . Here we show that Cyp7a1 mRNA levels are very rapidly reduced following FXR activation, indicative of a post-transcriptional mechanism. We identify the RNA binding protein Zfp36l1 as an FXR target gene and show that hepatic overexpression of ZFP36L1 in mice decreases Cyp7a1 mRNA levels. In contrast, Zfp36l1 L -KO mice have increased levels of Cyp7a1 mRNA and biliary Bile Acids as well as reduced plasma cholesterol levels. Zfp36l1 L -KO mice fed a Western diet have reduced diet-induced obesity and steatosis, likely due to impaired lipid absorption, consistent with increased Cyp7a1 levels. Thus, the ZFP36L1-dependent regulation of Bile Acid Metabolism is an important metabolic contributor of dyslipidemia, obesity and hepatosteatosis.
Martin R Turner – 3rd expert on this subject based on the ideXlab platform
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rna binding protein zfp36l1 maintains posttranscriptional regulation of Bile Acid Metabolism
Journal of Clinical Investigation, 2017Co-Authors: Elizabeth J Tarling, Bethan L Clifford, Joan Cheng, Pauline Morand, Angela Cheng, Ellen Lester, Tamer Sallam, Martin R Turner, Thomas Q De Aguiar VallimAbstract:: Bile Acids function not only as detergents that facilitate lipid absorption but also as signaling molecules that activate the nuclear receptor farnesoid X receptor (FXR). FXR agonists are currently being evaluated as therapeutic agents for a number of hepatic diseases due to their lipid-lowering and antiinflammatory properties. FXR is also essential for maintaining Bile Acid homeostasis and prevents the accumulation of Bile Acids. Elevated Bile Acids activate FXR, which in turn switches off Bile Acid synthesis by reducing the mRNA levels of Bile Acid synthesis genes, including cholesterol 7α-hydroxylase (Cyp7a1). Here, we show that FXR activation triggers a rapid posttranscriptional mechanism to degrade Cyp7a1 mRNA. We identified the RNA-binding protein Zfp36l1 as an FXR target gene and determined that gain and loss of function of ZFP36L1 reciprocally regulate Cyp7a1 mRNA and Bile Acid levels in vivo. Moreover, we found that mice lacking hepatic ZFP36L1 were protected from diet-induced obesity and steatosis. The reduced adiposity and antisteatotic effects observed in ZFP36L1-deficient mice were accompanied by impaired lipid absorption that was consistent with altered Bile Acid Metabolism. Thus, the ZFP36L1-dependent regulation of Bile Acid Metabolism is an important metabolic contributor to obesity and hepatosteatosis.
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abstract 402 post transcriptional regulation of Bile Acid Metabolism by the rna binding protein zfp36l1
Arteriosclerosis Thrombosis and Vascular Biology, 2017Co-Authors: Elizabeth J Tarling, Bethan L Clifford, Joan Cheng, Pauline Morand, Angela Cheng, Tamer Sallam, Martin R Turner, Thomas Q De Aguiar VallimAbstract:Bile Acids are detergents and important signaling molecules that activate the nuclear receptor FXR to control key metabolic processes, including feedback mechanisms to maintain Bile Acid homeostasis. Activation of FXR decreases the mRNA levels of several Bile Acid synthetic genes, including the rate-limiting enzyme Cyp7a1 . Here we show that Cyp7a1 mRNA levels are very rapidly reduced following FXR activation, indicative of a post-transcriptional mechanism. We identify the RNA binding protein Zfp36l1 as an FXR target gene and show that hepatic overexpression of ZFP36L1 in mice decreases Cyp7a1 mRNA levels. In contrast, Zfp36l1 L -KO mice have increased levels of Cyp7a1 mRNA and biliary Bile Acids as well as reduced plasma cholesterol levels. Zfp36l1 L -KO mice fed a Western diet have reduced diet-induced obesity and steatosis, likely due to impaired lipid absorption, consistent with increased Cyp7a1 levels. Thus, the ZFP36L1-dependent regulation of Bile Acid Metabolism is an important metabolic contributor of dyslipidemia, obesity and hepatosteatosis.