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Identification of a nutrient sensing transcriptional network in monocytes by using inbred rat models of cafeteria diet

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Title: Identification of a nutrient sensing transcriptional network in monocytes by using inbred rat models of cafeteria diet
Authors: Martinez-Micaelo, N
Gonzalez-Abuin, N
Terra, X
Ardevol, A
Pinent, M
Petretto, E
Behmoaras, JV
Item Type: Journal Article
Abstract: Obesity has reached pandemic levels worldwide. The current models of dietinduced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy dense foods that are prevalent in Western society. We and others have shown that cafeteria diet (CAF) is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat. We have previously shown that inbred rat strains such as Wistar Kyoto (WKY) and Lewis (LEW) show different susceptibilities to CAF diets with distinct metabolic and morphometric profiles. Here we show a difference in plasma MCP-1 levels and investigate the effect of CAF diet on peripheral blood monocyte transcriptome as powerful stress-sensing immune cells in WKY and LEW rats. We found that 75.5% of the differentially expressed transcripts under CAF diet were up-regulated in WKY rats and were functionally related to the activation of the immune response. Using a gene co-expression network constructed from the genes differentially expressed between CAF diet-fed LEW and WKY rats, we identified the Acyl-CoA synthetase short-chain family member 2 (Acss2) as a hub gene for a nutrient sensing cluster of transcripts in monocytes. Acss2 genomic region is significantly enriched for previously established metabolism quantitative trait loci in the rat. Notably, monocyte expression levels of Acss2 significantly correlated with plasma glucose, triglyceride, leptin and NEFA levels as well as morphometric measurements such as body weight and the total fat following CAF in the rat. These results show the importance of the genetic background in nutritional genomics and identify inbred rat strains as potential models for CAF-induced obesity.
Issue Date: 13-Jul-2016
Date of Acceptance: 4-Jul-2016
URI: http://hdl.handle.net/10044/1/34475
DOI: https://dx.doi.org/10.1242/dmm.025528
ISSN: 1754-8403
Publisher: Company of Biologists
Start Page: 1231
End Page: 1239
Journal / Book Title: Disease Models & Mechanisms
Volume: 9
Copyright Statement: © 2016. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Sponsor/Funder: Kidney Research UK
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: RP9/2013
MR/M004716/1
MR/N01121X/1
Keywords: Cafeteria diet
Inbred rats
LEW
Monocyte transcriptome
WKY
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Department of Medicine
Faculty of Medicine



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