Roles of lectin-like oxidized low-density lipoprotein (LDL) receptor-1 for maintenance of normal glucose tolerance in normal and obese states
Rieko Takanabe-Mori1, Koh Ono2, Naoya Sowa1, Hiromichi Wada1, Tomohide Takaya2, Noriko Satoh1, Akira Shimatsu1, Masatoshi Fujita2, Tatsuya Sawamura3, Koji Hasegawa1.
- Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- Graduate School of Medicine, Kyoto University, Kyoto, Japan.
- National Cardiovascular Center, Osaka, Japan.
American Heart Association Scientific Sessions 2009 (Orlando, USA), 2009/11/18 (Poster).
Abstract
Background: Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is a receptor for oxidized LDL (ox-LDL). LOX-1 is strongly expressed in endothelial cells in the early stages of atherosclerosis. In mouse adipocytes, LOX-1 is known to be induced by PPARγ ligands, and to increase ox-LDL uptake, cholesterol accumulation, and fatty acid uptake. It has been reported that plasma soluble LOX-1 levels are increased in obese women. We have also found that the expression of LOX-1 in adipose tissue is greater in high-fat diet-induced obese mice than those fed normal chow. However, the role of LOX-1 in the maintenance of normal glucose tolerance is unknown. The present study investigated such a function of LOX-1 using LOX-1 knockout mice (KO).
Methods and Results: Eight-week-old LOX-1 KO and wild-type mice (WT, C57BL/6) were fed a high-fat diet or normal chow for eight weeks. LOX-1 KO tended to be thinner compared with WT after feeding them the normal chow or high-fat diet. The weights of both visceral and subcutaneous fats were significantly (p < 0.05) decreased in LOX-1 KO compared to WT. However, the decrease in weight was more prominent for mesenteric (30%) than subcutaneous (20%) fat. The fasting blood glucose level was significantly (p < 0.05) lower in LOX-1 KO (95 mg/dl) than in WT (133 mg/dl) fed normal chow. By employing the intraperitoneal glucose tolerance test, however, we demonstrated that the blood glucose level at 60 minutes after glucose administration was significantly higher in LOX-1 KO (361 mg/dl) than WT (290 mg/dl). Glucose tolerance was impaired both in LOX-1 KO and WT fed the high-fat diet compared with those fed normal chow. However, the glucose level at 60 minutes after glucose administration was similar between LOX-1 KO (460 mg/dl) and WT (449 mg/dl).
Conclusions: LOX-1 KO showed a decreased visceral fat weight and impaired glucose tolerance, suggesting that LOX-1 is required for the development of adipose tissue and maintenance of normal glucose tolerance. The decreased uptake of cholesterol and fatty acids in the adipose tissue of LOX-1 KO may contribute to their impaired glucose tolerance in the normal state. However, the extent of the high-fat diet-induced impairment of glucose tolerance appeared to be lower in LOX-1 KO than WT.