Roles of lectin-like oxidized low-density lipoprotein (LDL) receptor-1 for maintenance of normal glucose tolerance in normal and obese states

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.

  1. Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  3. 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.