LOX-1 is required for overexpression of MCP-1 in mesenteric fat tissue of obese mice
Rieko Takanabe-Mori1, Koh Ono2, Naoya Sowa2, Hiromichi Wada1, Tomohide Takaya2, Noriko Satoh3, Akira Shimatsu1, Masatoshi Fujita4, Tatsuya Sawamura5, Koji Hasegawa1.
- Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
- Division of Diabetic Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
- Department of Vascular Physiology, National Cardiovascular Center, Osaka, Japan.
第74回日本循環器学会学術集会 (京都), 2010/03/06 (口演).
Abstract
Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is one of the scavenger receptors, and induced by inflammatory cytokines and oxidative stress. Recently, we have found that the mice adipose tissue expression of LOX-1 is increased by feeding high-fat diet in association with body and mesenteric fat weights. In addition, the expression level of LOX-1 is closely correlated with that of monocyte chemoattractant protein-1 (MCP-1) (p < 0.0001, r = 0.909), a proinflammatory cytokine, which plays a key role in the pathogenesis of obesity and metabolic syndrome. The present study examined a cause-effect relationship of LOX-1 with MCP-1 using LOX-1-knockout mice (LOX-1-KO).
Methods and Results: Eight-week-old LOX-1-KO and wild-type mice (WT) were fed a high-fat diet or normal chow for 16 weeks. By feeding high-fat diet, body weight similarly increased in WT (29%) and LOX-1-KO (31%). The MCP-1 expression levels in the mesenteric fat tissue were markedly increased (3.2-fold, p < 0.05) in WT fed a high-fat diet compared with normal chow. The MCP-1 levels in LOX-1-KO mice were lower than those in WT. Notably, in high-fat diet-induced obese mice, the MCP-1 level in LOX-1-KO decreased by 47% (p < 0.05) compared with the level in WT.
Conclusions: LOX-1 is required for the mice adipose tissue overexpression of MCP-1 induced by high-fat diet. LOX-1 may be involved in the inflammatory process of the adipose tissue in obesity.