Insulin resistance induced by a high-fat diet is associated with the induction of genes related to leukocyte activation in rat peripheral leukocytes

AimsInsulin resistance caused by a high-fat diet induces type 2 diabetes and its complications. In this study, we investigated gene expression changes in peripheral leukocytes with insulin resistance by conducting microarray analyses in rats with high-fat diet-induced insulin resistance.Main methodsAfter assessing insulin resistance in rats by an oral glucose tolerance test, we performed microarray analyses using peripheral leukocytes from normal rats and insulin-resistant rats after fasting. Real-time RT-PCR analyses were performed for several upregulated genes in the microarray data after fasting and at 3 h after a single oral glucose load.Key findingsFeeding rats a high-fat diet for 77 days induced moderate insulin resistance. Microarray analysis showed that the high-fat diet enhances many genes related to leukocyte activation. These upregulated genes included genes related to host defense, and many genes related to G-protein-coupled receptor/tyrosine receptor signaling. Moreover, many genes, such as Anxa1, S100a8, Il22ra2, Gng10, Csf3r and Cd302, showed further upregulation of their expression after a single oral glucose load. Exposure to high glucose and/or tumor necrosis factor-α which is known to be a factor that induces insulin resistance, enhanced the mRNA levels of DUSP1, ANXA1, IL1B, S100A8, IL22RA2, S100A9 and IRF1 in human monocyte-like U937 cells.SignificanceThese results suggest that the expression of genes related to leukocyte activation in peripheral leukocytes is associated with the development of moderate insulin resistance.