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Targeting the alternative bile acid synthetic pathway for metabolic diseases
The gut microbiota is profoundly involved in glucose and lipid metabolism, in part by regulating bile acid (BA) metabolism and affecting multiple BA-receptor signaling pathways. BAs are synthesized in the liver by multi-step reactions catalyzed via two distinct routes, the classical pathway (produci...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Higher Education Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106556/ https://www.ncbi.nlm.nih.gov/pubmed/33252713 http://dx.doi.org/10.1007/s13238-020-00804-9 |
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author | Jia, Wei Wei, Meilin Rajani, Cynthia Zheng, Xiaojiao |
author_facet | Jia, Wei Wei, Meilin Rajani, Cynthia Zheng, Xiaojiao |
author_sort | Jia, Wei |
collection | PubMed |
description | The gut microbiota is profoundly involved in glucose and lipid metabolism, in part by regulating bile acid (BA) metabolism and affecting multiple BA-receptor signaling pathways. BAs are synthesized in the liver by multi-step reactions catalyzed via two distinct routes, the classical pathway (producing the 12α-hydroxylated primary BA, cholic acid), and the alternative pathway (producing the non-12α-hydroxylated primary BA, chenodeoxycholic acid). BA synthesis and excretion is a major pathway of cholesterol and lipid catabolism, and thus, is implicated in a variety of metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease. Additionally, both oxysterols and BAs function as signaling molecules that activate multiple nuclear and membrane receptor-mediated signaling pathways in various tissues, regulating glucose, lipid homeostasis, inflammation, and energy expenditure. Modulating BA synthesis and composition to regulate BA signaling is an interesting and novel direction for developing therapies for metabolic disease. In this review, we summarize the most recent findings on the role of BA synthetic pathways, with a focus on the role of the alternative pathway, which has been under-investigated, in treating hyperglycemia and fatty liver disease. We also discuss future perspectives to develop promising pharmacological strategies targeting the alternative BA synthetic pathway for the treatment of metabolic diseases. |
format | Online Article Text |
id | pubmed-8106556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Higher Education Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81065562021-05-11 Targeting the alternative bile acid synthetic pathway for metabolic diseases Jia, Wei Wei, Meilin Rajani, Cynthia Zheng, Xiaojiao Protein Cell Review The gut microbiota is profoundly involved in glucose and lipid metabolism, in part by regulating bile acid (BA) metabolism and affecting multiple BA-receptor signaling pathways. BAs are synthesized in the liver by multi-step reactions catalyzed via two distinct routes, the classical pathway (producing the 12α-hydroxylated primary BA, cholic acid), and the alternative pathway (producing the non-12α-hydroxylated primary BA, chenodeoxycholic acid). BA synthesis and excretion is a major pathway of cholesterol and lipid catabolism, and thus, is implicated in a variety of metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease. Additionally, both oxysterols and BAs function as signaling molecules that activate multiple nuclear and membrane receptor-mediated signaling pathways in various tissues, regulating glucose, lipid homeostasis, inflammation, and energy expenditure. Modulating BA synthesis and composition to regulate BA signaling is an interesting and novel direction for developing therapies for metabolic disease. In this review, we summarize the most recent findings on the role of BA synthetic pathways, with a focus on the role of the alternative pathway, which has been under-investigated, in treating hyperglycemia and fatty liver disease. We also discuss future perspectives to develop promising pharmacological strategies targeting the alternative BA synthetic pathway for the treatment of metabolic diseases. Higher Education Press 2020-11-30 2021-05 /pmc/articles/PMC8106556/ /pubmed/33252713 http://dx.doi.org/10.1007/s13238-020-00804-9 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Jia, Wei Wei, Meilin Rajani, Cynthia Zheng, Xiaojiao Targeting the alternative bile acid synthetic pathway for metabolic diseases |
title | Targeting the alternative bile acid synthetic pathway for metabolic diseases |
title_full | Targeting the alternative bile acid synthetic pathway for metabolic diseases |
title_fullStr | Targeting the alternative bile acid synthetic pathway for metabolic diseases |
title_full_unstemmed | Targeting the alternative bile acid synthetic pathway for metabolic diseases |
title_short | Targeting the alternative bile acid synthetic pathway for metabolic diseases |
title_sort | targeting the alternative bile acid synthetic pathway for metabolic diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106556/ https://www.ncbi.nlm.nih.gov/pubmed/33252713 http://dx.doi.org/10.1007/s13238-020-00804-9 |
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