Abstract 1375: Expression of LOX-1 (OLR1) is Markedly Increased in the Adipose Tissue of High-fat Diet-induced Obese Mice in Close Association With MCP-1
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is a receptor for oxidized LDL induced by inflammatory cytokines and oxidative stress. LOX-1 is strongly expressed in endothelial cells at early stages of atherosclerosis, and is suggested to be an inducer of a proinflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1). It has been reported that LOX-1 expression in adipocytes is induced during differentiation in culture, and that plasma soluble LOX-1 levels are increased in obese women. It has also been proposed that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in the adipose tissue. However, the expression of LOX-1 in the adipose tissue of high-fat diet-induced obese (HFD) mice has not been investigated. We examined LOX-1 mRNA levels in the mesenteric fat of C57BL/6 mice fed a high-fat diet for eight weeks using RT-PCR, and analyzed their relationship with those of obesity-related genes. Compared with mice fed normal chow (NC), the body weight increased in HFD mice by 32%, and the mesenteric fat weight increased 2.9-fold. HFD mice were also associated with impaired glucose tolerance and high plasma levels of insulin and leptin, clearly indicating a state of insulin resistance. LOX-1 mRNA levels in adipose tissue were markedly (3.6-fold) increased in HFD compared to NC mice (p<0.05). The fat LOX-1 levels were correlated with the body weight (R=0.704, p=0.0005), mesenteric fat weight (R=0.703, p=0.0005), and plasma leptin levels (R=0.892, p<0.0001). While mRNA levels of aP2 and PPARγ, adipocyte differentiation markers, were increased in HFD compared with NC mice, these levels were not correlated with those of LOX-1. Notably, the fat mRNA levels of LOX-1 were most closely correlated with those of MCP-1 (R=0.909, p<0.0001). These findings demonstrate that LOX-1 expression in the adipose tissue is induced by high-fat diet intake in close association with MCP-1 expression. The results also suggest that LOX-1, together with MCP-1, is involved in chronic inflammation of the adipose tissue in obese mice showing insulin resistance.