Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet-induced systemic inflammation, microglial activation, and reduced neuroplasticity.

Abstract

The goal of this study was to identify the intrinsic links that explain the effect of a Western diet (WD) on cognitive dysfunction. Specific pathogen-free, wild-type mice were fed either a control diet (CD) or a high-fat, high-sucrose WD after weaning and were euthanized at 10 mo of age to study the pathways that affect cognitive health. The results showed that long-term WD intake reduced hippocampal synaptic plasticity and the level of brain-derived neurotrophic factor mRNA in the brain and isolated microglia. A WD also activated ERK1/2 and reduced postsynaptic density-95 in the brain, suggesting postsynaptic damage. Moreover, WD-fed mice had increased inflammatory signaling in the brain, ileum, liver, adipose tissue, and spleen, which was accompanied by microglia activation. In the brain, as well as in the digestive tract, a WD reduced signaling regulated by retinoic acid and bile acids (BAs), whose receptors form heterodimers to control metabolism and inflammation. Furthermore, a WD intake caused dysbiosis and dysregulated BA synthesis with reduced endogenous ligands for BA receptors, i.e., farnesoid X receptor and G-protein-coupled bile acid receptor in the liver and brain. Together, dysregulated BA synthesis and dysbiosis were accompanied by systemic inflammation, microglial activation, and reduced neuroplasticity induced by WD.-Jena, P. K., Sheng, L., Di Lucente, J., Jin, L.-W., Maezawa, I., Wan, Y.-J. Y. Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet-induced systemic inflammation, microglial activation, and reduced neuroplasticity.

• Authors: Prasant Kumar Jena, Lili Sheng, Jacopo Di Lucente, Lee-Way Jin, Izumi Maezawa, Yu-Jui Yvonne Wan
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 32 Issue 5 Pg. 2866-2877 (05 2018) ISSN: 1530-6860 [Electronic] United States
• PMID: 29401580 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Bile Acids and Salts
• Receptors, Cytoplasmic and Nuclear
• farnesoid X-activated receptor
• Tretinoin
• Mapk1 protein, mouse
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Bile Acids and Salts (biosynthesis)
• Diet, Western (adverse effects)
• Dysbiosis (chemically induced, metabolism, pathology)
• Hippocampus (metabolism, pathology)
• Inflammation (chemically induced, metabolism, pathology)
• MAP Kinase Signaling System
• Male
• Mice
• Microglia (metabolism, pathology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Neuronal Plasticity
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Tretinoin (metabolism)