Infiltration of M1 Macrophages into Adipose Tissue of ddY-H Mice Preceding Spontaneous Appearances of Insulin Resistance

Abstract

We have isolated insulin resistant mice (ddY-H mice) which are spontaneously induced at 12-weeks of age even if fed with the standard chow pellets. Since accumulated evidences have suggested that an appearance of insulin resistance is associated with obesity and a state of inflammation in adipose tissue, the present study investigated an appearance of macrophages in adipose tissue of ddY-H mice. Although ddY-H mice were fed the standard chow pellets ad libitam, increases in body weight, adipose tissue mass, and fat cell size were observed. In adipose tissues of ddY-H mice, gene expression of monocyte chemoattractant protein-1 (MCP-1) elevated slightly at 5-weeks of age and was maintained at higher levels at 9- and 12-weeks of age, and MCP-1 content in adipose tissue increased 2-fold at 12-weeks of age. Also, increased gene expressions of CD68 and F4/80, markers of macrophage, in adipose tissue were observed at 9-weeks of age. In addition, F4/80 positive cells were histologically found in adipose tissue at 15-weeks of age but not at 7-weeks of age, suggesting an increased infiltration of macrophage into adipose tissue. In adipose tissue of ddY-H mice, gene expressions of CD11c and toll-like receptor 4 (TLR4), markers of proinflammatory macrophages (M1), markedly increased although those of CD163 and mannose receptor (MR), markers of anti-inflammatory macrophages (M2), did not change. These results suggest that proinflammatory (M1) macrophages infiltrate into enlarged adipose tissues of ddY-H mice, which is preceding spontaneous appearance of insulin resistance.