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

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

Rieko Takanabe-Mori1, Koh Ono2, Yukiko Abe1, Hiromichi Wada1, Tomohide Takaya1, Noriko Satoh1, Akira Shimatsu1, Masatoshi Fujita2, Tatsuya Sawamura3, Koji Hasegawa1.

  1. Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  3. National Cardiovascular Center, Osaka, Japan.

American Heart Association Scientific Sessions 2009 (Orlando, USA), 2009/11/17 (Poster).

Abstract

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.