Vitamin A Absorption, Storage and Mobilization

Abstract

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.

Retinal-chitosan Conjugates Effectively Deliver Active Chromophores to Retinal Photoreceptor Cells in Blind Mice and Dogs

“…The dog, and other carnivores, differ from other mammals in their circulatory vitamin A transport (Raila et al, 2002). In this respect, vitamin A metabolism in mice more closely resembles the conditions in humans (Blaner et al, 2016). A pilot study of oral administration of the 9-cis-RAL-CM-chitosan conjugate failed to rescue photoreceptor function in the RPE65-deficient dog, most likely because of the vitamin A transport peculiarities in this species.…”

Lipid droplet functions beyond energy storage

“…More is known about vitamin A (retinol), a precursor of the nuclear receptor ligand retinoic acid. Vitamin A is esterified with FAs and accumulates in the core of LDs as retinyl esters [61-64]. The droplets of hepatic stellate cells are a major storage site for 70-80% of vitamin A in the body.…”

“…These hepatic droplet stores ensure that there is a constant supply of vitamin A during periods of dietary insufficiency. Smaller quantities of retinyl esters are also stored in the LDs of extrahepatic stellate cells in the intestine, lung, and kidney as well as in hepatocytes and adipocytes [61, 62, 64-66]. Retinol is released from retinyl-esters by the action of retinyl-ester hydrolases [63, 67].…”

Recent insights on the role and regulation of retinoic acid signaling during epicardial development

“…To meet tissue demands for retinol, REs from hepatic stellate cells are hydrolyzed and transferred to hepatocytes for export (reviewed in (Blaner et al, 2016). Over the years, multiple enzymes have been proposed to carry out REs hydrolysis from intracellular stores; however, ablation of any one single intracellular lipase did not dramatically affect the conversion of REs to retinol in vivo (Grumet, Eichmann, et al, 2016;Taschler et al, 2015;Tuohetahuntila et al, 2016).…”