Retinol-binding protein 2 (RBP2): More than just dietary retinoid uptake.

Retinol-binding protein 2 (RBP2, also known as cellular retinol-binding protein 2 (CRBP2)) is a member of the fatty acid-binding protein family and has been extensively studied for its role in facilitating dietary vitamin A (retinol) uptake and metabolism within enterocytes of the small intestine. RBP2 is present in highest concentrations in the proximal small intestine where it constitutes approximately 0.1–0.5% of soluble protein. Recent reports have established that RBP2 binds monoacylglycerols (MAGs) with high affinity, including the canonical endocannabinoid 2-arachidonoylglycerol (2-AG). Crystallographic studies reveal that retinol, 2-AG, or other long-chain MAGs alternatively can bind in the retinol-binding pocket of RBP2. It also has been demonstrated recently that Rbp2 -deficient mice are more susceptible to developing obesity and associated metabolic phenotypes when exposed to a high fat diet, or as they age when fed a conventional chow diet. When subjected to an oral fat challenge, the Rbp2 -deficient mice release into the circulation significantly more, compared to littermate controls, of the intestinal hormone glucose-dependent insulinotropic polypeptide (GIP). These new findings regarding RBP2 structure and actions within the intestine are the focus of this review. • RBP2 binds 2-monoacylglycerols with very high affinity, equivalent to that of retinol binding. • 2-Monoacylglycerol and retinol bind in the same binding pocket of RBP2. • RBP2 modulates the intestinal release of glucose-dependent insulinotropic polypeptide (GIP) in response to a fat challenge. • The absence of RBP2 renders mice more prone to the development of obesity and associated metabolic diseases. [ABSTRACT FROM AUTHOR]