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Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice
Chronic inflammation is considered a causal risk factor predisposing to insulin resistance. However, evidence is accumulating that inflammation confined to the liver may not be causal to metabolic dysfunction. To investigate this, we assessed if hepatic inflammation explains the predisposition towar...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359820/ https://www.ncbi.nlm.nih.gov/pubmed/25815343 http://dx.doi.org/10.1155/2015/956854 |
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author | Gruben, Nanda Funke, Anouk Kloosterhuis, Niels J. Schreurs, Marijke Sheedfar, Fareeba Havinga, Rick Houten, Sander M. Shiri-Sverdlov, Ronit van de Sluis, Bart Kuivenhoven, Jan Albert Koonen, Debby P. Y. Hofker, Marten H. |
author_facet | Gruben, Nanda Funke, Anouk Kloosterhuis, Niels J. Schreurs, Marijke Sheedfar, Fareeba Havinga, Rick Houten, Sander M. Shiri-Sverdlov, Ronit van de Sluis, Bart Kuivenhoven, Jan Albert Koonen, Debby P. Y. Hofker, Marten H. |
author_sort | Gruben, Nanda |
collection | PubMed |
description | Chronic inflammation is considered a causal risk factor predisposing to insulin resistance. However, evidence is accumulating that inflammation confined to the liver may not be causal to metabolic dysfunction. To investigate this, we assessed if hepatic inflammation explains the predisposition towards insulin resistance in low-density lipoprotein receptor knock-out (Ldlr (−/−)) mice. For this, wild type (WT) and Ldlr (−/−) mice were fed a chow diet, a high fat (HF) diet, or a high fat, high cholesterol (HFC) diet for 2 weeks. Plasma lipid levels were elevated in chow-fed Ldlr (−/−) mice compared to WT mice. Although short-term HF or HFC feeding did not result in body weight gain and adipose tissue inflammation, dyslipidemia was worsened in Ldlr (−/−) mice compared to WT mice. In addition, dyslipidemic HF-fed Ldlr (−/−) mice had a higher hepatic glucose production rate than HF-fed WT mice, while peripheral insulin resistance was unaffected. This suggests that HF-fed Ldlr (−/−) mice suffered from hepatic insulin resistance. While HFC-fed Ldlr (−/−) mice displayed the anticipated increased hepatic inflammation, this did neither exacerbate systemic nor hepatic insulin resistance. Therefore, our results show that hepatic insulin resistance is unrelated to cholesterol-induced hepatic inflammation in Ldlr (−/−) mice, indicating that hepatic inflammation may not contribute to metabolic dysfunction per se. |
format | Online Article Text |
id | pubmed-4359820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-43598202015-03-26 Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice Gruben, Nanda Funke, Anouk Kloosterhuis, Niels J. Schreurs, Marijke Sheedfar, Fareeba Havinga, Rick Houten, Sander M. Shiri-Sverdlov, Ronit van de Sluis, Bart Kuivenhoven, Jan Albert Koonen, Debby P. Y. Hofker, Marten H. J Diabetes Res Research Article Chronic inflammation is considered a causal risk factor predisposing to insulin resistance. However, evidence is accumulating that inflammation confined to the liver may not be causal to metabolic dysfunction. To investigate this, we assessed if hepatic inflammation explains the predisposition towards insulin resistance in low-density lipoprotein receptor knock-out (Ldlr (−/−)) mice. For this, wild type (WT) and Ldlr (−/−) mice were fed a chow diet, a high fat (HF) diet, or a high fat, high cholesterol (HFC) diet for 2 weeks. Plasma lipid levels were elevated in chow-fed Ldlr (−/−) mice compared to WT mice. Although short-term HF or HFC feeding did not result in body weight gain and adipose tissue inflammation, dyslipidemia was worsened in Ldlr (−/−) mice compared to WT mice. In addition, dyslipidemic HF-fed Ldlr (−/−) mice had a higher hepatic glucose production rate than HF-fed WT mice, while peripheral insulin resistance was unaffected. This suggests that HF-fed Ldlr (−/−) mice suffered from hepatic insulin resistance. While HFC-fed Ldlr (−/−) mice displayed the anticipated increased hepatic inflammation, this did neither exacerbate systemic nor hepatic insulin resistance. Therefore, our results show that hepatic insulin resistance is unrelated to cholesterol-induced hepatic inflammation in Ldlr (−/−) mice, indicating that hepatic inflammation may not contribute to metabolic dysfunction per se. Hindawi Publishing Corporation 2015 2015-02-28 /pmc/articles/PMC4359820/ /pubmed/25815343 http://dx.doi.org/10.1155/2015/956854 Text en Copyright © 2015 Nanda Gruben et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Gruben, Nanda Funke, Anouk Kloosterhuis, Niels J. Schreurs, Marijke Sheedfar, Fareeba Havinga, Rick Houten, Sander M. Shiri-Sverdlov, Ronit van de Sluis, Bart Kuivenhoven, Jan Albert Koonen, Debby P. Y. Hofker, Marten H. Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice |
title | Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice |
title_full | Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice |
title_fullStr | Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice |
title_full_unstemmed | Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice |
title_short | Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice |
title_sort | cholesterol-induced hepatic inflammation does not underlie the predisposition to insulin resistance in dyslipidemic female ldl receptor knockout mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359820/ https://www.ncbi.nlm.nih.gov/pubmed/25815343 http://dx.doi.org/10.1155/2015/956854 |
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