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

• Published in: Life sciences (1973) 2010-12, Vol.87 (23), p.679-685
• Main Authors: Fujimoto, Saki, Mochizuki, Kazuki, Shimada, Masaya, Hori, Tomoyo, Murayama, Yuki, Ohashi, Norio, Goda, Toshinao
• Format: Article
• Language: English
• Subjects: Animals; Dietary Fats - toxicity; Glucose - administration & dosage; Glucose Tolerance Test; High-fat diet; Humans; Inflammation; Insulin resistance; Insulin Resistance - genetics; Leukocytes - metabolism; Male; Microarray; Microarray Analysis; Monocytes - metabolism; Peripheral leukocyte; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Signal Transduction - genetics; Tumor Necrosis Factor-alpha - administration & dosage; U937 Cells; Up-Regulation
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2010.10.001

Insulin 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. After 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. Feeding 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. These results suggest that the expression of genes related to leukocyte activation in peripheral leukocytes is associated with the development of moderate insulin resistance.