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Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling

A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world’s population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the...

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Autores principales: Ren, Zi-Lin, Li, Chang-Xiang, Ma, Chong-Yang, Chen, Dan, Chen, Jia-Hui, Xu, Wen-Xiu, Chen, Cong-Ai, Cheng, Fa-Feng, Wang, Xue-Qian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654021/
https://www.ncbi.nlm.nih.gov/pubmed/36361829
http://dx.doi.org/10.3390/ijms232113045
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author Ren, Zi-Lin
Li, Chang-Xiang
Ma, Chong-Yang
Chen, Dan
Chen, Jia-Hui
Xu, Wen-Xiu
Chen, Cong-Ai
Cheng, Fa-Feng
Wang, Xue-Qian
author_facet Ren, Zi-Lin
Li, Chang-Xiang
Ma, Chong-Yang
Chen, Dan
Chen, Jia-Hui
Xu, Wen-Xiu
Chen, Cong-Ai
Cheng, Fa-Feng
Wang, Xue-Qian
author_sort Ren, Zi-Lin
collection PubMed
description A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world’s population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood–brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.
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spelling pubmed-96540212022-11-15 Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling Ren, Zi-Lin Li, Chang-Xiang Ma, Chong-Yang Chen, Dan Chen, Jia-Hui Xu, Wen-Xiu Chen, Cong-Ai Cheng, Fa-Feng Wang, Xue-Qian Int J Mol Sci Review A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world’s population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood–brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently. MDPI 2022-10-27 /pmc/articles/PMC9654021/ /pubmed/36361829 http://dx.doi.org/10.3390/ijms232113045 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ren, Zi-Lin
Li, Chang-Xiang
Ma, Chong-Yang
Chen, Dan
Chen, Jia-Hui
Xu, Wen-Xiu
Chen, Cong-Ai
Cheng, Fa-Feng
Wang, Xue-Qian
Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling
title Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling
title_full Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling
title_fullStr Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling
title_full_unstemmed Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling
title_short Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling
title_sort linking nonalcoholic fatty liver disease and brain disease: focusing on bile acid signaling
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654021/
https://www.ncbi.nlm.nih.gov/pubmed/36361829
http://dx.doi.org/10.3390/ijms232113045
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