Introduction:
Retinol-binding protein 4 (RBP-4) is a circulating adipokine associated with insulin resistance, obesity and cardiovascular risk. Previous evidence suggests a negative impact on insulin sensitivity via an interaction with the insulin-stimulated glucose transporter (GLUT-4), specifically in adipocytes. Since angiotensin-2 (ANG-2) impairs GLUT-4 presentation and insulin sensitivity, we hypothesized that renin-angiotensin system (RAS) activity might affect RBP-4 expression as well. Furthermore, both RAS activity and insulin sensitivity are affected by dietary salt, but the relationship between these factors and RBP-4 expression is unknown. We hypothesized that liberal salt diet, via suppression of RAS activity, would be associated with reduced RBP-4 levels compared to salt restriction.
METHODS:
Healthy subjects (7 men, 7 women, mean age 24 yr, BMI 22.6) were studied on low salt (LS 10 mmol Na/day) diet and then liberal salt (HS 200 mmol Na/day) diet for 1 week each. Samples were drawn after overnight rest in the supine position for plasma renin activity (PRA), serum Aldosterone (Aldo) and plasma RBP-4 and again after ANG-2 infusion (3ng/kg/min x 45 mins).
Results:
Salt manipulation predictably modified RAS activity (HS v. LS Aldo, 4.5 ± 3.8 v. 19.5 ± 8.5 ng/dl [p<0.01]; HS v. LS PRA, 0.5 ± 0.4 v. 2.7 ± 1.4 ng/ml/hr [p<0.01]). RBP-4 was significantly lower on a HS compared to LS diet (35.4 ± 6.6 v. 38.6 ± 7.9 mg/L, p= 0.017). No significant change was observed in RBP-4 level after ANG-2 infusion on either diet. Fasting insulin levels trended lower on HS compared to LS (3.9 ± 6.8 v. 4.4 ± 1.2 μIU/ml, p=0.09), but there was no difference in fasting glucose (81.9 ± 6.8 v. 82.1 ± 4.7 mg/dl, p=0.92).
Conclusion:
RBP-4 levels are modified by dietary salt intake. RBP-4 levels were lower under HS conditions (suppressed RAS) as compared to LS conditions. Acute administration of ANG-2 does not increase RBP-4 levels in this healthy population. Insulin response was similar to prior reports suggesting that the connection between RAS activity, dietary salt and insulin sensitivity may include RBP-4. Future work exploring the relationship between RBP-4, GLUT-4 and insulin sensitivity should take into consideration the effect of dietary salt intake.
Activation of the Renin-Angiotensin System Mediates the Effects of Dietary Salt Intake on Atherogenesis in the Apolipoprotein E Knockout Mouse
