Retinol-binding protein 4 (RBP4), primarily secreted by liver and adipose tissue, has been linked with non-alcoholic fatty liver disease (NAFLD). However, investigations on the relationships between RBP4 and NAFLD have produced inconsistent results. Therefore, the association between serum RBP4 levels and the development or regression of NAFLD was prospectively investigated.

A total of 3389 Chinese adults, aged 40–75 years and followed-up for 3.09 years, were included and analyzed in the study. NAFLD was diagnosed by abdominal ultrasonography. Serum RBP4 levels were measured, and their relationship to NAFLD development and regression assessed.

Of the 1318 participants without NAFLD at baseline, 410 developed NAFLD after follow-up. Baseline RBP4 was positively associated with incident NAFLD: the fully adjusted odds ratio (OR) was 2.01 with a 95% confidence interval (CI) of 1.33–3.04 (P = 0.003 for trend). After follow-up, a significant increase in RBP4 levels was observed in participants who developed NAFLD. On the other hand, in 1382 subjects diagnosed with NAFLD at baseline, 339 experienced NAFLD regression after follow-up. Thus, baseline RBP4 was inversely associated with NAFLD regression: the fully adjusted OR was 0.52 with a 95% CI of 0.34–0.80 (P < 0.001 for trend). A significant decrease in RBP4 after follow-up was also noted in participants with NAFLD regression.

Serum RBP4 concentrations are associated with the development and regression of NAFLD, making them a potential novel preventative and therapeutic target in NAFLD management.