title: Changes in cardiac lipid metabolism during sepsis: the essential role of very low-density lipoprotein receptors.
abstract: OBJECTIVE
  Sepsis accompanies myocardial dysfunction and dynamic alterations of cardiac metabolism. We have recently demonstrated that the very low-density lipoprotein receptor (VLDL-R), which is abundantly expressed in the heart, plays a key role in energy metabolism of the fasting heart. However, little is known about the function and regulation of the VLDL-R during sepsis. In the present study, we explored lipid accumulation and VLDL-R expression in the lipopolysaccharide (LPS)-stimulated heart in vivo and regulation of VLDL-R expression in vitro.
  
  
  RESULTS
  Electron microscopy and immunohistochemistry demonstrated that LPS significantly decreased both lipid accumulation and VLDL-R expression in the hearts of fasting mice. Treatment with LPS also downregulated VLDL-R in rat neonatal cardiac myocytes, and this downregulation was completely reversed by interleukin (IL)-1beta receptor antagonist. IL-1beta downregulated the expression of VLDL-R in a time- and dose-dependent manner and markedly reduced the uptake of DiI-labeled beta-VLDL but not DiI-labeled low-density lipoprotein (LDL). Use of specific pharmacologic inhibitors and short interference RNA revealed that Hsp90 was required for IL-1beta to downregulate VLDL-R expression.
  
  
  CONCLUSIONS
  These findings suggest that IL-1beta is a principle mediator of changes in cardiac lipid and energy metabolism during sepsis through the downregulation of myocardial VLDL-R expression.
authors.affiliation: Department of Organ Regeneration, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Lijing
authors.initials: L
authors.lastname: Jia
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Morimoto
authors.forename: Sadao
authors.initials: S
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Izawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Ise
authors.forename: Tadao
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
authors.forename: Kou-Juey
authors.initials: KJ
authors.lastname: Wu
authors.forename: Uichi
authors.initials: U
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D015536:Down-Regulation; D005215:Fasting; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007375:Interleukin-1 / Q000378:metabolism; D050356:Lipid Metabolism; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D007375:Interleukin-1; D018942:Macrolides; D034741:RNA, Small Interfering; D011973:Receptors, LDL; C036053:VLDL receptor; C035359:monorden