title: Acute psychological stress accelerates reverse cholesterol transport via corticosterone-dependent inhibition of intestinal cholesterol absorption.
abstract: BACKGROUND
  Psychological stress is associated with an increased risk of cardiovascular diseases. However, the connecting mechanisms of the stress-inducing activation of the hypothalamic-pituitary-adrenal axis with atherosclerosis are not well-understood.
  
  
  OBJECTIVE
  To study the effect of acute psychological stress on reverse cholesterol transport (RCT), which transfers peripheral cholesterol to the liver for its ultimate fecal excretion.
  
  
  RESULTS
  C57Bl/6J mice were exposed to restraint stress for 3 hours to induce acute psychological stress. RCT in vivo was quantified by measuring the transfer of [(3)H]cholesterol from intraperitoneally injected mouse macrophages to the lumen of the small intestine within the stress period. Surprisingly, stress markedly increased the contents of macrophage-derived [(3)H]cholesterol in the intestinal lumen. In the stressed mice, intestinal absorption of [(14)C]cholesterol was significantly impaired, the intestinal mRNA expression level of peroxisome proliferator-activated receptor-α increased, and that of the sterol influx transporter Niemann-Pick C1-like 1 decreased. The stress-dependent effects on RCT rate and peroxisome proliferator-activated receptor-α gene expression were fully mimicked by administration of the stress hormone corticosterone (CORT) to nonstressed mice, and they were blocked by the inhibition of CORT synthesis in stressed mice. Moreover, the intestinal expression of Niemann-Pick C1-like 1 protein decreased when circulating levels of CORT increased. Of note, when either peroxisome proliferator-activated receptor α or liver X receptor α knockout mice were exposed to stress, the RCT rate remained unchanged, although plasma CORT increased. This indicates that activities of both transcription factors were required for the RCT-accelerating effect of stress.
  
  
  CONCLUSIONS
  Acute psychological stress accelerated RCT by compromising intestinal cholesterol absorption. The present results uncover a novel functional connection between the hypothalamic-pituitary-adrenal axis and RCT that can be triggered by a stress-induced increase in circulating CORT.
authors.affiliation: Wihuri Research Institute, Kalliolinnatie 4, Helsinki 00140, Finland.
authors.forename: Reija
authors.initials: R
authors.lastname: Silvennoinen
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escola-Gil
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.forename: Noemi
authors.initials: N
authors.lastname: Rotllan
authors.forename: Gemma
authors.initials: G
authors.lastname: Llaverias
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.forename: Annabel F
authors.initials: AF
authors.lastname: Valledor
authors.forename: Jianming
authors.initials: J
authors.lastname: He
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee-Rueckert
mesh_terms: D000208:Acute Disease; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism* / Q000493:pharmacokinetics; D003345:Corticosterone / Q000097:blood* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007421:Intestine, Small / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D008055:Lipids; D000071518:Liver X Receptors; D026901:Membrane Transport Proteins; C000605213:NR1H3 protein, human; C482445:Npc1l1 protein, mouse; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D002784:Cholesterol; D003345:Corticosterone