Expression of carboxylesterase and lipase genes in rat liver cell-types

Abstract

Approximately 80% of the body vitamin A is stored in liver stellate cells with in the lipid droplets as retinyl esters. In low vitamin A status or after liver injury, stellate cells are depleted of the stored retinyl esters by their hydrolysis to retinol. However, the identity of retinyl ester hydrolase(s) expressed in stellate cells is unknown. The expression of carboxylesterase and lipase genes in purified liver cell-types was investigated by real-time PCR. We found that six carboxylesterase and hepatic lipase genes were expressed in hepatocytes. Adipose triglyceride lipase was expressed in Kupffer cells, stellate cells and endothelial cells. Lipoprotein lipase expression was detected in Kupffer cells and stellate cells. As a function of stellate cell activation, expression of adipose triglyceride lipase decreased by 2-fold and lipoprotein lipase increased by 32-fold suggesting that it may play a role in retinol ester hydrolysis during stellate cell activation. KeywordsHepatic stellate cells; carboxylesterases; lipoprotein lipase; adipocytes triglyceride lipase; real-time PCR; retinyl palmitate; vitamin A Liver plays an important role in the uptake, metabolism and storage of vitamin A (Figure 1). The first step in liver vitamin A metabolism is sequestration of the chylomicrons remnants in the space of Disse [1]. Lipoprotein lipase and hepatic lipase are secreted in the space of Disse and can further hydrolyze chylomicrons remnants. Hepatocytes are responsible for the uptake of retinyl ester containing chylomicrons remnants [2]. Inside the hepatocytes, the retinyl esters are hydrolyzed to retinol [3] which can either be oxidized to retinoic acid or bound to cellular retinol binding protein (CRBP). Retinol secreted into the circulatory system, binds retinol binding protein (RBP) [4] and is transported to the tissues to meet the body's retinol requirements. The excess RBP-bound retinol will be taken up by the hepatic stellate cells (HSC) and converted by lecithin-retinol acyltransferase or coenzyme A retinol acyltransferase to Correspondence, Sonal P. Sanghani, BRTC L3-314, 1345 W. 16 th Street, Indianapolis, IN-46202, Email: ssanghan@iupui.edu, Phone: 317-274-6647, Fax: 317-278-9739. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. [16;17]. It is our hypothesis that intervention of vitamin A loss might lead to treatment option for liver fibrosis. However, the target enzyme responsible for increased retinyl ester hydrolysis has not been identified. Accordingly, the expression of six carboxylesterase and six lipase genes was studied to determine the liver cell-spec...

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