Roles of lectin-like oxidized low-density lipoprotein receptor-1 for glucose tolerance in normal and obese mice

Roles of lectin-like oxidized low-density lipoprotein receptor-1 for glucose tolerance in normal and 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), 2010/03/07 (口演).

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a receptor for multiple ligands, and involved in atherosclerosis. In mouse adipocytes, LOX-1 is induced during differentiation and increases fatty acid uptake. We have found that the expression of LOX-1 in the mouse adipose tissue is increased by feeding high-fat diet (HFD) in proportion to body weight and plasma leptin levels. However, roles of LOX-1 for glucose tolerance in normal and obese mice are unknown. LOX-1-knockout mice (LOX-1-KO) and wild-type mice (WT) were fed HFD or normal chow (NC) for 16 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed at two time points, 8 and 16 weeks after feeding HFD/NC. Body weight was similarly increased by HFD in both LOX-1-KO (31%) and WT (29%). In mice fed NC, IPGTT demonstrated impaired glucose tolerance in LOX-1-KO compared with WT (p < 0.05). However, blood levels were similar between LOX-1-KO and WT fed HFD for 8 weeks. In LOX-1-KO, surprisingly, glucose intolerance significantly (p < 0.05) improved at 16 weeks after feeding HFD compared with the intolerance at 8 weeks. However, the intolerance did not improve from 8 to 16 weeks in WT. In conclusion, under the state of NC, LOX-1 is required for the maintenance of normal glucose tolerance. However, LOX-1 may be involved in the impairment of glucose tolerance at the late stage of HFD-induced obesity.