Context: Administration of retinol-binding protein 4 (RBP-4) impairs insulin sensitivity in animals, and elevated serum concentrations have been associated with insulin resistance in humans.

Objective: We have studied whether weight loss influences RBP-4.

Patients and methods: Fasting serum concentrations of RBP-4 were measured before and 6 months after gastric banding surgery in 33 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls. To characterize the association of weight loss with central and peripheral appetite regulation, the signaling protein agouti-related protein (AGRP), the orexigenic hormone ghrelin, and its recently identified antagonist obestatin were determined.

Results: At baseline, RBP-4 levels were markedly higher in obese than in lean subjects (2.7 +/- 0.5 vs. 0.9 +/- 0.5 microg/ml; P < 0.001). In contrast, AGRP and obestatin were lower in obese subjects compared with lean controls (all P < 0.001). Six months after gastric banding, BMI was reduced to 40 +/- 5 kg/m(2), RBP-4 was reduced to 2.0 +/- 0.7 microg/ml, AGRP increased from 1.8 +/- 1.1 to 3.4 +/- 1.1 ng/ml, ghrelin increased from 93 +/- 58 to 131 +/- 70 pg/ml, and obestatin increased from 131 +/- 52 to 173 +/- 35 pg/ml (all P < 0.05). Individual changes of RBP-4 were associated with changes of BMI (r = 0.72), the homeostasis model assessment insulin resistance-index (r = 0.53), and total cholesterol (r = 0.42, for all P < 0.05).

Conclusion: Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. This is accompanied by favorable changes in appetite-regulating hormones, which might support the sustained weight loss after obesity surgery.