Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation

Abstract This study aims to uncover how specific bacteria and bile acids (BAs) contribute to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both genders. A control diet (CD) and Western diet (WD), which contains high fat and carbohydrate, were used to feed wild type (WT) and...

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Main Authors: Lili Sheng, Prasant Kumar Jena, Hui-Xin Liu, Karen M. Kalanetra, Frank J. Gonzalez, Samuel W. French, Viswanathan V. Krishnan, David A. Mills, Yu-Jui Yvonne Wan
Format: Article
Language:English
Published: Nature Portfolio 2017-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-01576-9
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author Lili Sheng
Prasant Kumar Jena
Hui-Xin Liu
Karen M. Kalanetra
Frank J. Gonzalez
Samuel W. French
Viswanathan V. Krishnan
David A. Mills
Yu-Jui Yvonne Wan
author_facet Lili Sheng
Prasant Kumar Jena
Hui-Xin Liu
Karen M. Kalanetra
Frank J. Gonzalez
Samuel W. French
Viswanathan V. Krishnan
David A. Mills
Yu-Jui Yvonne Wan
author_sort Lili Sheng
collection DOAJ
description Abstract This study aims to uncover how specific bacteria and bile acids (BAs) contribute to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both genders. A control diet (CD) and Western diet (WD), which contains high fat and carbohydrate, were used to feed wild type (WT) and FXR knockout (KO) mice followed by phenotyping characterization as well as BA and microbiota profiling. Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and highest hepatic and serum lipids as well as insulin resistance among the eight studied groups. Gender differences in WD-induced steatosis, insulin sensitivity, and predicted microbiota functions were all FXR-dependent. FXR deficiency enriched Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, which were accompanied by increased hepatic taurine-conjugated cholic acid and β-muricholic acid as well as hepatic and serum lipids. Additionally, distinct microbiota profiles were found in WD-fed WT mice harboring simple steatosis and CD-fed FXR KO mice, in which the steatosis had a potential to develop into liver cancer. Together, the presented data revealed FXR-dependent concomitant relationships between gut microbiota, BAs, and metabolic diseases in both genders. Gender differences in BAs and microbiota may account for gender dissimilarity in metabolism and metabolic diseases.
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spelling doaj.art-a1f3563fbf034791a338a08f1e1a6ac32022-12-21T22:59:31ZengNature PortfolioScientific Reports2045-23222017-05-017111210.1038/s41598-017-01576-9Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR InactivationLili Sheng0Prasant Kumar Jena1Hui-Xin Liu2Karen M. Kalanetra3Frank J. Gonzalez4Samuel W. French5Viswanathan V. Krishnan6David A. Mills7Yu-Jui Yvonne Wan8Department of Medical Pathology and Laboratory Medicine, University of CaliforniaDepartment of Medical Pathology and Laboratory Medicine, University of CaliforniaDepartment of Medical Pathology and Laboratory Medicine, University of CaliforniaDepartment of Food Science and Technology, Department of Viticulture and Enology, University of CaliforniaLaboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIHDepartment of Pathology, Harbor UCLA Medical CenterDepartment of Medical Pathology and Laboratory Medicine, University of CaliforniaDepartment of Food Science and Technology, Department of Viticulture and Enology, University of CaliforniaDepartment of Medical Pathology and Laboratory Medicine, University of CaliforniaAbstract This study aims to uncover how specific bacteria and bile acids (BAs) contribute to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both genders. A control diet (CD) and Western diet (WD), which contains high fat and carbohydrate, were used to feed wild type (WT) and FXR knockout (KO) mice followed by phenotyping characterization as well as BA and microbiota profiling. Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and highest hepatic and serum lipids as well as insulin resistance among the eight studied groups. Gender differences in WD-induced steatosis, insulin sensitivity, and predicted microbiota functions were all FXR-dependent. FXR deficiency enriched Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, which were accompanied by increased hepatic taurine-conjugated cholic acid and β-muricholic acid as well as hepatic and serum lipids. Additionally, distinct microbiota profiles were found in WD-fed WT mice harboring simple steatosis and CD-fed FXR KO mice, in which the steatosis had a potential to develop into liver cancer. Together, the presented data revealed FXR-dependent concomitant relationships between gut microbiota, BAs, and metabolic diseases in both genders. Gender differences in BAs and microbiota may account for gender dissimilarity in metabolism and metabolic diseases.https://doi.org/10.1038/s41598-017-01576-9
spellingShingle Lili Sheng
Prasant Kumar Jena
Hui-Xin Liu
Karen M. Kalanetra
Frank J. Gonzalez
Samuel W. French
Viswanathan V. Krishnan
David A. Mills
Yu-Jui Yvonne Wan
Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation
Scientific Reports
title Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation
title_full Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation
title_fullStr Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation
title_full_unstemmed Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation
title_short Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation
title_sort gender differences in bile acids and microbiota in relationship with gender dissimilarity in steatosis induced by diet and fxr inactivation
url https://doi.org/10.1038/s41598-017-01576-9
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