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Sci Rep. 2017 May 11;7(1):1748. doi: 10.1038/s41598-017-01576-9.

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

Author information

1
Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
2
Department of Food Science and Technology, Department of Viticulture and Enology, University of California, Davis, CA, USA.
3
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
4
Department of Pathology, Harbor UCLA Medical Center, Torrance, CA, USA.
5
Department of Chemistry, College of Science and Mathematics, Fresno State University, Fresno, CA, USA.
6
Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA. yjywan@ucdavis.edu.

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.

PMID:
28496104
PMCID:
PMC5431816
DOI:
10.1038/s41598-017-01576-9
[Indexed for MEDLINE]
Free PMC Article

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