TY - JOUR
T1 - Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet-induced systemic inflammation, microglial activation, and reduced neuroplasticity
AU - Jena, Prasant Kumar
AU - Sheng, Lili
AU - Di Lucente, Jacopo
AU - Jin, Lee-Way
AU - Maezawa, Izumi
AU - Wan, Yu-Jui Yvonne
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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 10mo 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 brainderived neurotrophic factor mRNA in the brain and isolated microglia. AWD 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 bymicroglia 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. Further more, 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.
AB - 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 10mo 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 brainderived neurotrophic factor mRNA in the brain and isolated microglia. AWD 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 bymicroglia 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. Further more, 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.
KW - Alzheimer's disease
KW - Cognition
KW - FXR
KW - Gut microbiota
KW - TGR5
UR - http://www.scopus.com/inward/record.url?scp=85047419394&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047419394&partnerID=8YFLogxK
U2 - 10.1096/fj.201700984RR
DO - 10.1096/fj.201700984RR
M3 - Article
C2 - 29401580
AN - SCOPUS:85047419394
VL - 32
SP - 2866
EP - 2877
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 5
ER -