The Biochemistry of Retinoid Signaling II

William S. Blaner, Yang Li, Pierre-Jacques Brun, Jason J. Yuen, Seung-Ah Lee, Robin D. Clugston, Blaner, William S., Li, Yang, Brun, Pierre-Jacques, Yuen, Jason J., Lee, Seung-Ah, Clugston, Robin D.

Mary Ann Asson-Batres, Cecile Rochette-Egly

It is well established that chylomicron remnant (dietary) vitamin A is taken up from the circulation by hepatocytes, but more than 80 % of the vitamin A in the liver is stored in hepatic stellate cells (HSC). It presently is not known how vitamin A is transferred from hepatocytes to HSCs for storage. Since retinol-binding protein 4 (RBP4), a protein that is required for mobilizing stored vitamin A, is synthesized solely by hepatocytes and not HSCs, it similarly is not known how vitamin A is transferred from HSCs to hepatocytes. Although it has long been thought that RBP4 is absolutely essential for delivering vitamin A to tissues, recent research has proven that this notion is incorrect since total RBP4-deficiency is not lethal. In addition to RBP4, vitamin A is also found in the circulation bound to lipoproteins and as retinoic acid bound to albumin. It is not known how these different circulating pools of vitamin A contribute to the vitamin A needs of different tissues. In our view, better insight into these three issues is required to better understand vitamin A absorption, storage and mobilization. Here, we provide an up to date synthesis of current knowledge regarding the intestinal uptake of dietary vitamin A, the storage of vitamin A within the liver, and the mobilization of hepatic vitamin A stores, and summarize areas where our understanding of these processes is incomplete.