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Toxicol Lett. 2018 May 1;287:10-22. doi: 10.1016/j.toxlet.2018.01.006. Epub 2018 Jan 31.

Diabetic cognitive dysfunction is associated with increased bile acids in liver and activation of bile acid signaling in intestine.

Author information

1
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
2
Chinese Materia Medica College, Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
3
Chinese Materia Medica College, Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: zhuangpengwei@163.com.
4
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: youcai.zhang@tju.edu.cn.

Abstract

Impaired regulation of bile acid (BA) homeostasis has been suggested to be associated with adverse metabolic consequences. However, whether BA homeostasis is altered in diabetes-induced cognitive dysfunction (DCD) remains unknown. In the present study, mice were divided into four groups, namely normal control (NC) group, high-fat diet (HFD) group, diabetes without cognitive dysfunction (unDCD) group, and DCD group. Compared to HFD mice, the concentration of total BAs in liver was higher in unDCD and DCD mice, due to increased intestinal BA absorption. DCD mice tended to have higher BA concentrations in both liver and ileum than unDCD mice. Consequently, DCD mice had increased basolateral BA efflux (Ostα, Ostβ, and Mrp4) and decreased BA synthesis (Cyp7a1, Cyp8b1, and Cyp7b1) in the liver as well as activated Fxr-Fgf15 signaling in the ileum. DCD mice also had increased BA hydroxylation (Cyp3a11) and BA sulfation (Sult2a1) in the liver compared to HFD mice. Furthermore, the bacterial community composition was altered in the cecum of DCD mice, characterized with a marked increase in Defferribacteres and Candidatus Saccharibacteria. In summary, the present study provides the first comprehensive analysis of BA homeostasis in DCD mice, and revealed a potential role of BAs in DCD development.

KEYWORDS:

Bacteria; Bile acid; Diabetes-induced cognitive dysfunction; High-fat diet

PMID:
29382564
DOI:
10.1016/j.toxlet.2018.01.006
[Indexed for MEDLINE]

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