Abstract 15097: LOX-1 is Required for the Adiposal Expression of Proinflammatory Cytokines in High-fat Diet-induced Obese Mice
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is a receptor for oxidized LDL, and is strongly expressed in endothelial cells at an early stage of atherosclerosis. LOX-1 expression in adipocytes is induced by PPARγ ligands and appears to be involved in adipocyte cholesterol metabolism. However, the role of adipose tissue LOX-1 in high-fat diet-induced obesity is unknown. We found that mRNA levels of adiposal LOX-1 were markedly (3.6-fold) increased in obese mice fed a high-fat diet (HFD) compared with those fed normal chow (NC). The levels were closely correlated with those of a proinflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1, R=0.909, p=0.0001). However, mRNA levels of LOX-1 showed no correlation with adipocyte differentiation markers, PPARγ (R=0.170, p=0.4739) and aP2 (R=0.072, p=0.7627). Then, LOX-1 knockout (LOX-1-KO) and wild-type (WT) mice were fed HFD or NC for 16 weeks. HFD feeding increased the body weight similarly in WT (29%) and LOX-1-KO (30%) mice. The mesenteric fat expression levels of proinflammatory cytokines such as MCP-1, macrophage inflammatory protein-1α (MIP-1α), and interleukin-6 (IL-6) were markedly increased in WT mice fed HFD compared with WT mice fed NC (MCP-1: 3.2-fold, p<0.05, MIP-1α: 2.3-fold, p<0.05, IL-6: 1.5-fold, p<0.05). However, in LOX-1-KO mice, HFD-induced expressions of these cytokines were significantly less than WT mice. Decreases of the expression in HFD-LOX-1-KO mice compared with HFD-WT mice were 51% (p<0.05) for MCP-1, 42% (p<0.05) for MIP-1α, and 36% (p<0.05) for IL-6. We performed IPGTT and compared the blood glucose levels in WT and LOX-1-KO mice for 8 and 16 weeks after the start of HFD feeding. The glucose levels tended to be lower in LOX-1-KO than WT mice at 16 weeks. In LOX-1-KO mice, blood glucose levels at 60 min after glucose loading were significantly (p<0.05) lower at 16 weeks (404±19 mg/dl) than at 8 weeks (465±20 mg/dl). In Conclusions, LOX-1 is required for the HFD-induced expression of proinflammatory cytokines such as MCP-1, MIP-1α, and IL-6 in the adipose tissue of obese mice. LOX-1 may be involved in the impairment of glucose tolerance at later stages of HFD-induced obesity as well as in the inflammatory process of the adipose tissue.
- © 2010 by American Heart Association, Inc.