Retinol binding protein 4 (RBP4; RBP) is a 21kDa secreted protein and member of the lipocalin family. It is known as the primary transporter of retinol (vitamin A) to tissues. Recently, a report revealed RBP4 as an adipokine linking glucose transporter 4 (GLUT4) suppression in adipose tissue and insulin resistance. GLUT4 downregulation in adipocytes is a common feature of different insulin resistant states and knockout mice develop systemic insulin resistance. RBP4 expression is increased in the adipose tissue of these mice, and RBP4 serum levels have been shown to be elevated in insulin-resistant mice and in obese and type-2 diabetic subjects. RBP4 overexpression and injection into wild-type mice causes insulin resistance. In contrast to the clear results obtained from animal studies, reports about human RBP4 generated conflicting results. While some reports claim that RBP4 serum levels correlate with BMI and insulin resistance, other reports found no relationship. Recently, the multitransmembrane domain protein STRA6 has been identified as the RBP4 receptor. Retinaldehyde, a converted product of retinol has been recently shown to be a metabolically active signal inhibiting adipogenesis and improving insulin sensitivity.
Lipocalin-2 (neutrophil gelatinaseassociated lipocalin, siderocalin, 24p3, uterocalin) is a 25kDa protein which belongs to the same superfamily of lipocalins as RBP4. Recently, lipocalin-2 has been identified as an inflammatory marker closely related to obesity and its metabolic complications.
Figure: Retinaldehyde, an intermediate in vitamin A metabolism, is a metabolically active signal. (a) Vitamin A metabolism. (b) More than half of the vitamin A in the body is stored in the liver. In blood, vitamin A is transported as a complex with transthyretin (TTR) and retinol-binding proteins (RBPs), such as RBP4, which is secreted by the adipose tissue. Retinol is imported into adipose tissue, lungs and kidneys by a receptor-mediated process. Adapted from: The hydrogen highway to reperfusion therapy: K.C. Wood & M.T. Gladwin; Nat. Med. 13, 673 (2007).
