Serum levels of retinol-binding protein 4 and risk of colon adenoma

Dear Editor, Obesity is now considered as a convincing and probable cause for colorectal neoplasia (World Cancer Research Fund 2011). Insulin resistance is a key mechanism linking obesity to colon carcinogenesis (Giovannucci E 2001). Supporting evidence for this notion includes data from a number of epidemiological studies showing risk association of colon cancer and adenoma with insulin resistance-associated biomarkers, such as insulin, insulin-like growth factors (IGFs), adipokines (e.g., leptin, adiponectin) and inflammatory cytokines (e.g., IL-6, TNF-α) (Giovannucci E 2001; Sandhu MS, Dunger DB, et. al 2002; Ortiz AP, Thompson CL, et. al 2012). Retinol-binding protein 4 (RBP4), a recently identified adipokine, has been shown to potentially have a causative effect on the development of insulin resistance (Yang Q, Graham TE, et al. 2005; Graham TE, Yang Q, et. al 2006). RBP4 increases expression of the glucose transporter, GLUT4, which facilitates the rate-limiting step in glucose uptake by skeletal muscle and adipocytes. In adipose tissue-specific GLUT4 knockout (adipose-GLUT4−/−) mice, secretion of RBP4 by adipocytes is greatly enhanced. Increased circulating levels of RBP4 suppress phosphoinositide-3-kinase (PI3K) in muscle cells, and in the liver, stimulate the expression of phosphoenolpyruvate carboxykinase (PEPCK), inducing systemic insulin resistance. Treatment of adipose-GLUT4−/− mice with rosiglitazone, an insulin sensitizer, reduced the elevated RBP4 mRNA levels in adipose tissue and completely normalized the serum RBP4 levels (Yang Q, Graham TE, et. al 2005). In humans, subcutaneous adipocyte GLUT4 protein levels correlated positively with the rate of glucose disposal and inversely with serum levels of RBP4 (Graham TE, Yang Q, et. al 2006). Despite the emerging evidence for a causal link of RBP4 to insulin resistance, no previous study has investigated the relationship between RBP4 and colon neoplasia. Therefore, we carried out a cross-sectional study to examine the hypothesis that high levels of RBP4 are associated with an increased risk of colon adenoma.