High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation

Kristine C. McGrath, Xiao Hong Li, Phillippa T. Whitworth, Robert Kasz, Joanne Tan, Susan V. McLennan, David S. Celermajer, Philip J. Barter, Kerry Anne Rye, Alison K. Heather

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation.

LanguageEnglish
Pages421-430
Number of pages10
JournalJournal of Lipid Research
Volume55
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

McGrath, Kristine C. ; Li, Xiao Hong ; Whitworth, Phillippa T. ; Kasz, Robert ; Tan, Joanne ; McLennan, Susan V. ; Celermajer, David S. ; Barter, Philip J. ; Rye, Kerry Anne ; Heather, Alison K. / High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation. In: Journal of Lipid Research. 2014 ; Vol. 55, No. 3. pp. 421-430.
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abstract = "Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation.",
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McGrath, KC, Li, XH, Whitworth, PT, Kasz, R, Tan, J, McLennan, SV, Celermajer, DS, Barter, PJ, Rye, KA & Heather, AK 2014, 'High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation', Journal of Lipid Research, vol. 55, no. 3, pp. 421-430. https://doi.org/10.1194/jlr.M043281

High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation. / McGrath, Kristine C.; Li, Xiao Hong; Whitworth, Phillippa T.; Kasz, Robert; Tan, Joanne; McLennan, Susan V.; Celermajer, David S.; Barter, Philip J.; Rye, Kerry Anne; Heather, Alison K.

In: Journal of Lipid Research, Vol. 55, No. 3, 01.01.2014, p. 421-430.

Research output: Contribution to journalArticle

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AU - Li, Xiao Hong

AU - Whitworth, Phillippa T.

AU - Kasz, Robert

AU - Tan, Joanne

AU - McLennan, Susan V.

AU - Celermajer, David S.

AU - Barter, Philip J.

AU - Rye, Kerry Anne

AU - Heather, Alison K.

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N2 - Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation.

AB - Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation.

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