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

Journal of Lipid Research
Kristine C-Y McGrathAlison K Heather

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 i...Continue Reading

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Citations

Oct 15, 2014·International Immunopharmacology·Jingyuan LiHaiying Huang
Jul 30, 2014·International Immunopharmacology·Yunhe FuNaisheng Zhang
Dec 15, 2015·Current Opinion in Lipidology·John K Bielicki
Sep 22, 2015·Frontiers in Pharmacology·Kuang-Yuh Chyu, Prediman K Shah
Dec 22, 2014·Biochemical and Biophysical Research Communications·Gyun Jee SongKyung-Hyun Cho
Jul 17, 2014·Diabetes·Willeke de HaanMichael R Hayden
Feb 8, 2018·Journal of Nanobiotechnology·Hui ChenStella M Valenzuela
Feb 6, 2019·International Journal of Molecular Sciences·Karen Alejandra Méndez-LaraJosep Julve
Jan 1, 2020·Journal of the American Heart Association·Bikash ManandharKerry-Anne Rye
Nov 9, 2019·Endocrine, Metabolic & Immune Disorders Drug Targets·Shuang YaoGuanghua Luo
Sep 5, 2020·Journal of Food Science·Ryota HosomiKenji Fukunaga
Nov 20, 2015·Frontiers in Pharmacology·Andrew L SiebelBronwyn A Kingwell
Feb 6, 2020·Biochemical and Biophysical Research Communications·Gulce SariThomas Vanwolleghem

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Methods Mentioned

BETA
transgenic
ubiquitination
enzyme-linked immunosorbent assay
transfections
nuclear translocation
transcription factor assay
PCR
ELISA

Software Mentioned

Quantity One
PathScan

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