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

McGrath, KC; Li, XH; Whitworth, PT; Kasz, R; Tan, JT; McLennan, SV; Celermajer, DS; Barter, PJ; Rye, KA; Heather, AK

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

McGrath, KC

Li, XH Whitworth, PT Kasz, R Tan, JT McLennan, SV Celermajer, DS Barter, PJ Rye, KA Heather, AK

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Publication Type:: Journal Article
Citation:: Journal of Lipid Research, 2014, 55 (3), pp. 421 - 430
Issue Date:: 2014-01-01

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Field	Value	Language
dc.contributor.author	McGrath, KC https://orcid.org/0000-0002-6244-3929	en_US
dc.contributor.author	Li, XH	en_US
dc.contributor.author	Whitworth, PT	en_US
dc.contributor.author	Kasz, R	en_US
dc.contributor.author	Tan, JT	en_US
dc.contributor.author	McLennan, SV	en_US
dc.contributor.author	Celermajer, DS	en_US
dc.contributor.author	Barter, PJ	en_US
dc.contributor.author	Rye, KA	en_US
dc.contributor.author	Heather, AK	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	Journal of Lipid Research, 2014, 55 (3), pp. 421 - 430	en_US
dc.identifier.issn	0022-2275	en_US
dc.identifier.uri	http://hdl.handle.net/10453/32231
dc.description.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. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.	en_US
dc.relation.ispartof	Journal of Lipid Research	en_US
dc.relation.isbasedon	10.1194/jlr.M043281	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Liver	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Hepatitis, Animal	en_US
dc.subject.mesh	Insulin Resistance	en_US
dc.subject.mesh	Insulin	en_US
dc.subject.mesh	Phosphoenolpyruvate Carboxykinase (ATP)	en_US
dc.subject.mesh	Glucose	en_US
dc.subject.mesh	Blood Glucose	en_US
dc.subject.mesh	Triglycerides	en_US
dc.subject.mesh	Lipoproteins, HDL	en_US
dc.subject.mesh	Tumor Necrosis Factor-alpha	en_US
dc.subject.mesh	Apolipoprotein A-I	en_US
dc.subject.mesh	NF-kappa B	en_US
dc.subject.mesh	Interleukin-6	en_US
dc.subject.mesh	Glucose Tolerance Test	en_US
dc.subject.mesh	Reverse Transcriptase Polymerase Chain Reaction	en_US
dc.subject.mesh	Gene Expression	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Interferon-gamma	en_US
dc.subject.mesh	Diet, High-Fat	en_US
dc.title	High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	55	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	55	en_US

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. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

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http://hdl.handle.net/10453/32231