title: Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet.
abstract: Obesity has reached pandemic levels worldwide. The current models of diet-induced 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 the cafeteria (CAF) diet 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 the 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 the CAF diet were upregulated 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 acyl-CoA synthetase short-chain family member 2 (Acss2) as a hub gene for a nutrient-sensing cluster of transcripts in monocytes. The 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 non-esterified fatty acid (NEFA) levels as well as morphometric measurements such as body weight and the total fat following feeding with the CAF diet 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-diet-induced obesity.
authors.affiliation: Mobiofood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43003 Tarragona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Micaelo
authors.affiliation: Mobiofood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43003 Tarragona, Spain.
authors.forename: Noemi
authors.initials: N
authors.lastname: González-Abuín
authors.affiliation: Mobiofood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43003 Tarragona, Spain.
authors.forename: Ximena
authors.initials: X
authors.lastname: Terra
authors.affiliation: Mobiofood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43003 Tarragona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ardévol
authors.affiliation: Mobiofood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43003 Tarragona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pinent
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Republic of Singapore.
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.affiliation: Centre of Complement and Inflammation Research, Imperial College London, Du Cane Road, London W12 0NN, UK mteresa.blay@urv.cat Jacques.behmoaras@imperial.ac.uk.
authors.forename: Jacques
authors.identifier: 0000-0002-5170-2606
authors.initials: J
authors.lastname: Behmoaras
authors.affiliation: Mobiofood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43003 Tarragona, Spain mteresa.blay@urv.cat Jacques.behmoaras@imperial.ac.uk.
authors.forename: Mayte
authors.initials: M
authors.lastname: Blay
mesh_terms: D000818:Animals; D004032:Diet; D005502:Food; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D023281:Genomics; D008297:Male; D023421:Models, Animal; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D059467:Transcriptome / Q000235:genetics
chemical_list: D012333:RNA, Messenger
keywords: Cafeteria diet; Inbred rats; LEW; Monocyte transcriptome; WKY