NDLI: Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice

Content Provider	PubMed Central
Author	Gruben, Nanda Funke, Anouk Kloosterhuis, Niels J. Schreurs, Marijke Sheedfar, Fareeba Rick, Havinga Houten, Sander M. Shiri-sverdlov, Ronit Sluis, Bart Van De Albert, Kuivenhoven Jan Koonen, Debby P. Y. Hofker, Marten H.
Copyright Year	2015
Abstract	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.
Related Links	http://dx.doi.org/10.1155/2015/956854
Starting Page	956854
File Format	PDF
ISSN	23146745
e-ISSN	23146753
Journal	Journal of Diabetes Research
Volume Number	2015
Language	English
Publisher	Hindawi Publishing Corporation
Publisher Date	2015-01-01
Access Restriction	Open
Rights Holder	Hindawi Publishing Corporation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Endocrinology

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