Changes in cardiac lipid metabolism during sepsis: The essential role of very low-density lipoprotein receptors

Lijing Jia, Masafumi Takahashi, Hajime Morimoto, Sadao Takahashi, Atsushi Izawa, Hirohiko Ise, Tadao Iwasaki, Hiroaki Hattori, Kou Juey Wu, Uichi Ikeda

Research output: Contribution to journalArticle

17 Citations (Scopus)

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. Methods and 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)-1β receptor antagonist. IL-1β downregulated the expression of VLDL-R in a time- and dose-dependent manner and markedly reduced the uptake of DiI-labeled β-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-1β to downregulate VLDL-R expression. Conclusions: These findings suggest that IL-1β is a principle mediator of changes in cardiac lipid and energy metabolism during sepsis through the downregulation of myocardial VLDL-R expression.

Original languageEnglish
Pages (from-to)545-555
Number of pages11
JournalCardiovascular research
Volume69
Issue number2
DOIs
Publication statusPublished - Feb 1 2006

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Lipid Metabolism
Sepsis
Down-Regulation
Interleukin-1
Lipopolysaccharides
Energy Metabolism
Fasting
Lipids
VLDL receptor
Interleukin-1 Receptors
RNA Interference
LDL Lipoproteins
Cardiac Myocytes
Electron Microscopy
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Changes in cardiac lipid metabolism during sepsis : The essential role of very low-density lipoprotein receptors. / Jia, Lijing; Takahashi, Masafumi; Morimoto, Hajime; Takahashi, Sadao; Izawa, Atsushi; Ise, Hirohiko; Iwasaki, Tadao; Hattori, Hiroaki; Wu, Kou Juey; Ikeda, Uichi.

In: Cardiovascular research, Vol. 69, No. 2, 01.02.2006, p. 545-555.

Research output: Contribution to journalArticle

Jia, L, Takahashi, M, Morimoto, H, Takahashi, S, Izawa, A, Ise, H, Iwasaki, T, Hattori, H, Wu, KJ & Ikeda, U 2006, 'Changes in cardiac lipid metabolism during sepsis: The essential role of very low-density lipoprotein receptors', Cardiovascular research, vol. 69, no. 2, pp. 545-555. https://doi.org/10.1016/j.cardiores.2005.11.014
Jia, Lijing ; Takahashi, Masafumi ; Morimoto, Hajime ; Takahashi, Sadao ; Izawa, Atsushi ; Ise, Hirohiko ; Iwasaki, Tadao ; Hattori, Hiroaki ; Wu, Kou Juey ; Ikeda, Uichi. / Changes in cardiac lipid metabolism during sepsis : The essential role of very low-density lipoprotein receptors. In: Cardiovascular research. 2006 ; Vol. 69, No. 2. pp. 545-555.
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