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.