Dietary vitamin A is absorbed in the intestine where it is converted to retinyl ester. This retinyl ester is packaged along with other dietary lipids into nascent chylomicrons and secreted into the lymphatic system. Upon entering the general circulation the chyiomicrons undergo metabolism that gives dse to chylomicron remnants that are cleared from the circulation by liver and other tissues. Approximately 66-75% of chylomicron remnant retinyl ester is taken up by the liver where it is either resecreted into the circulation as retinol bound to retinol-binding protein (RBP) or stored in hepatic stellate cells. The remaining postprandial vitamin A is cleared by extrahepatic tissues. At present, there is only very limited understanding of the biochemistry that underlies the uptake and processing of postprandial vitamin A, either by the liver or by other tissues. Our studies will provide new biochemical understanding of these processes. We are proposing to identify factors and to investigate mechanisms responsible for the uptake and processing of postprandial vitamin A within the liver and in extrahepatic tissues, especially focusing on heart and mammary tissue. All of our studies will be carried out in knockout and transgenic mice.
In Aim 1, we propose to investigate how chylomicron remnant retinyl ester is taken up by hepatocytes and how the newly absorbed vitamin A is transferred from hepatocytes to hepatic stellate cells for storage. We will investigate the roles that RBP and cellular retinol-binding protein, type I (CRBPI) have in this process. Uptake of postprandial vitamin A into the heart will be examined in Aim 2. Unlike the liver, the heart does not store vitamin A. However, the heart has a relatively high need for retinoic acid for maintaining cellular health.
In Aim 2, we will examine the roles that RBP and cellular retinol-binding protein, type III (CRBPIII) have in facilitating cardiac retinoic acid synthesis from postprandial vitamin A and in retinol resecretion from the heart.
In Aim 3 we plan to explore how postprandial vitamin A is taken up and processed by mammary tissue for incorporation into milk. Our preliminary data indicates that postprandial vitamin A is an important source of the vitamin A present in milk. Here, we will focus on the roles that RBP, CRBPI, CRBPIII and lipoprotein lipase have in facilitating postprandial vitamin A incorporation into milk.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Nutrition Study Section (NTN)
Program Officer
May, Michael K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Internal Medicine/Medicine
Schools of Medicine
New York
United States
Zip Code
Lin, Jianguo; Zheng, Shizhong; Attie, Alan D et al. (2018) Perilipin 5 and liver fatty acid binding protein function to restore quiescence in mouse hepatic stellate cells. J Lipid Res 59:416-428
Belyaeva, Olga V; Wu, Lizhi; Shmarakov, Igor et al. (2018) Retinol dehydrogenase 11 is essential for the maintenance of retinol homeostasis in liver and testis in mice. J Biol Chem 293:6996-7007
Blaner, William S (2018) Hepatic Stellate Cells (HSCs) and Retinoids: Towards A Much More Defined Relationship. Hepatology :
Huang, Li-Shin; Yuen, Jason J; Trites, Michael J et al. (2018) Dietary Macronutrient Composition Determines the Contribution of DGAT1 to Alcoholic Steatosis. Alcohol Clin Exp Res 42:2298-2312
Ideta, Takayasu; Shirakami, Yohei; Ohnishi, Masaya et al. (2017) Non-alcoholic steatohepatitis-related liver tumorigenesis is suppressed in mice lacking hepatic retinoid storage. Oncotarget 8:70695-70706
Shmarakov, Igor O; Borschovetska, Vira L; Blaner, William S (2017) Hepatic Detoxification of Bisphenol A is Retinoid-Dependent. Toxicol Sci 157:141-155
Blaner, William S (2017) Acyl-CoA wax alcohol acyltransferase 2: its regulation and actions in support of color vision. J Lipid Res 58:633-635
Thompson, Spencer J; Sargsyan, Ashot; Lee, Seung-Ah et al. (2017) Hepatocytes Are the Principal Source of Circulating RBP4 in Mice. Diabetes 66:58-63
Blaner, William S (2017) Retinoid Actions: A New Horizon. Endocrinology 158:2719-2721
Blaner, William S; Gao, Madeleine A; Jiang, Hongfeng et al. (2017) Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling. Sci Rep 7:43474

Showing the most recent 10 out of 72 publications