Retinol Binding Protein 4 (RBP4) Levels Are Associated with Markers of Lipid Metabolism and Insulin Resistance in a British Cohort.

Retinol binding protein 4 (RBP4) is an adipokine that is up-regulated in the absence of GLUT4, and that increases liver and muscle insulin resistance in mice. In humans, high plasma levels of RBP4 have been correlated with several features of the metabolic syndrome in selected lean, obese or type 2 diabetes (T2D) groups. However individual correlations between RBP4 and specific metabolic indices have been inconsistent, perhaps in part because of different analytic methodologies for RBP4. This study aimed to assess the associations between RBP4 levels and metabolic phenotypes in a population-based cohort with a wide range of levels of insulin resistance, using a robust, commercially available nephelometric assay amenable to high throughput studies. Plasma RBP4 was measured in 198 participants of the MRC Ely study (age=54±5 yrs; Body mass index (BMI) = 26.8±4.4 kg/m²; including 14 people with T2D). Compared to controls, plasma RBP4 levels were higher in type 2 diabetics (4.24mg/l vs. 5.29 mg/l; p=0.003) as described previously. However, RBP4 levels were not different between non-obese (BMI<30) and obese (BMI±30) individuals (4.26mg/1 vs. 4.88mg/l; p=0.65). Regression analyses adjusted for age, sex, BMI and diabetes status showed positive associations between plasma RBP4 levels and triglycerides (p=0.0000001), cholesterol (p=0.00001), leptin (p=0.01) and fasting plasma glucose (p=0.07). High RBP4 levels were also positively associated with fasting plasma insulin (p=0.001) and negatively associated with HOMA-S (p=0.001). Our results demonstrate that RBP4 is strongly associated with features of the metabolic syndrome, particularly hypertriglyceridemia. We also replicated associations of high RBP4 levels .with increased insulin resistance in a population-based cohort. Further studies are required to understand the molecular bases of the link between RBP4, lipid metabolism and insulin resistance. [ABSTRACT FROM AUTHOR]