LOX-1 is required for overexpression of MCP-1 in mesenteric fat tissue of obese mice

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.

  1. Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  3. Division of Diabetic Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  4. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  5. 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.