Open AccessChronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice
Author(s) -
Silvennoinen Reija,
Quesada Helena,
Kareinen Ilona,
Julve Josep,
Kaipiainen Leena,
Gylling Helena,
BlancoVaca Francisco,
EscolaGil Joan Carles,
Kovanen Petri T.,
LeeRueckert Miriam
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12402
Subject(s) - cholesterol 7 alpha hydroxylase , bile acid , enterohepatic circulation , medicine , reverse cholesterol transport , endocrinology , farnesoid x receptor , cholesterol , excretion , corticosterone , chemistry , lipoprotein , biochemistry , transcription factor , hormone , nuclear receptor , gene
Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage‐specific reverse cholesterol transport, m‐ RCT ) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid‐treated animals, we investigated if chronic intermittent restraint stress would modify m‐ RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor ( FXR ), the bile salt export pump ( BSEP ), and the intestinal fibroblast growth factor 15 ( FGF 15) were reduced, whereas those of the ileal apical sodium‐dependent bile acid transporter ( ASBT ), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7 α ‐hydroxylase ( CYP 7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m‐ RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage‐derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m‐ RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m‐ RCT induction could have antiatherogenic potential under conditions of chronic stress.