LOX-1 is a scavenger receptor expressed in endothelial cells, smooth muscle cells, macrophages, and adipocytes (3
). Soluble LOX-1 is produced mainly by proteolytic cleavage of LOX-1 at the cell surface, and the expression of membrane-bound LOX-1 precedes the release of sLOX-1 (5
). Thus, plasma sLOX-1 may be a surrogate marker of cell-surface LOX-1 expression. We found that plasma sLOX-1 levels were elevated in obese women compared to lean and overweight women. As expected, the association between sLOX-1 and BMI appears to be mediated by the amount of fat mass. To our knowledge, this is the first study to report an association between sLOX-1 levels and obesity. While these findings are consistent with increased LOX-1 expression in obesity, the source of sLOX-1 in our women (vascular or adipose) cannot be determined.
Increased LOX-1 expression in obesity may be a physiological response to changes in adipocyte cholesterol content (3
). Cholesterol uptake in adipocytes occurs largely via the LDL receptor, but scavenger receptors are also important (3
). As adipocyte triglyceride storage increases, cholesterol is redistributed to the plasma membrane. This redistribution signals that the adipocyte is cholesterol-deficient and upregulates genes required for cholesterol synthesis and uptake, including possibly LOX-1 (3
). LOX-1 expression enhances ox-LDL and fatty acid uptake and increases adipocyte cholesterol content; however, if this occurs in excess, it could contribute to obesity (3
Two limitations in this study were the small sample size and the lack of direct measurements (e.g. adipocyte LOX-1 expression, cholesterol content, and cell size/number). Nevertheless, we had sufficient power to detect differences between lean and overweight women. Our findings that sLOX-1 levels are increased in obese women, along with previous findings that LOX-1 expression is increased in obese mice and induces ox-LDL and fatty acid uptake, support a role for LOX-1 in adipocyte metabolism. We believe that our study provides preliminary evidence for a relationship between sLOX-1 (i.e. LOX-1) and obesity in postmenopausal women. Future studies will need to determine whether LOX-1 is a consequence of or plays a role in the development of obesity.