High Circulating Retinol-Binding Protein 4 is Associated with Elevated Liver Fat, but not with Total-, Subcutaneous-, Visceral-, or Intramyocellular Fat in Humans

Abstract

Abstract Objective Retinol-binding protein 4 (RBP4) is an adipokine that induced insulin resistance in mice, and high plasma RBP4 levels were associated with insulin resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured circulating RBP4 in 75 healthy subjects and employed state of the art measurements of body fat distribution.

Abstract Research Design and Methods Total body-, visceral- and subcutaneous abdominal fat were determined by magnetic resonance (MR) tomography and liver fat and intramyocellular fat by ¹H-MR spectroscopy. Insulin sensitivity was measured by the euglycemic hyperinsulinemic clamp, and, together with insulin clearance estimated from the oral glucose tolerance test (OGTT).

Abstract Results Adjusted circulating RBP4 correlated negatively with insulin sensitivity (clamp: r=-0.33, p=0.005; OGTT: r=-0.36, p=0.002), and positively with parameters in the fasting state as insulin levels (r=0.35, p=0.003) and HOMA-IR (r=0.34, p=0.004). In addition, circulating RBP4 correlated negatively with hepatic insulin clearance (r=-0.25, p=0.04). Circulating RBP4 was not associated with total body-, visceral- and subcutaneous abdominal fat (all p ≥ 0.29). Plasma RBP4 levels were also not associated with intramyocellular fat, and circulating adiponectin or leptin. In contrast, plasma RBP4 levels correlated positively with liver fat in cross-sectional (r=0.27, p=0.03) and longitudinal analyses (r=0.37, p=0.04).

Abstract Conclusions Circulating RBP4 is not associated with the amount of fat in the classical depots or in the ectopic depots in muscle. However, it correlates positively with liver fat. Furthermore, metabolic parameters support the close relationship between circulating RBP4 with liver fat and presumably hepatic insulin resistance.