Cell surface heparan sulfate proteoglycans contribute to intracellular lipid accumulation in adipocytes

Wilsie, Chanchani Shree, Navaratna Deepti, Orlando

Description

Transport of fatty acids within the cytosol of adipocytes and their subsequent assimilation into lipid droplets has been thoroughly investigated; however, the mechanism by which fatty acids are transported across the plasma membrane from the extracellular environment remains unclear. Since triacylglycerol-rich lipoproteins represent an abundant source of fatty acids for adipocyte utilization, we have investigated the expression levels of cell surface lipoprotein receptors and their functional contributions toward intracellular lipid accumulation; these include very low density lipoprotein receptor (VLDL-R), low density lipoprotein receptor-related protein (LRP), and heparan sulfate proteoglycans (HSPG). Results We found that expression of these three lipoprotein receptors increased 5-fold, 2-fold, and 2.5-fold, respectively, during adipocyte differentiation. The major proteoglycans expressed by mature adipocytes are of high molecular weight (>500 kD) and contain both heparan and chondroitin sulfate moieties. Using ligand binding antagonists, we observed that HSPG, rather than VLDL-R or LRP, play a primary role in the uptake of DiI-lableled apoE-VLDL by mature adipocytes. In addition, inhibitors of HSPG maturation resulted in a significant reduction (>85%) in intracellular lipid accumulation. Conclusions These results suggest that cell surface HSPG is required for fatty acid transport across the plasma membrane of adipocytes.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2005
• Nombre de lectures: 0
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Lipids in Health and Disease Bio Med   Central

Research Open Access Cell surface heparan sulfat e proteoglycans contribute to intracellular lipid accumu lation in adipocytes Larissa C Wilsie, Shree Chanchani, Deep ti Navaratna and Robert A Orlando*

Address: Department of Biochemistry and Mo lecular Biology, University of New Mexico, Health Sciences Center, 915 Camino de Salu d, Albuquerque, New Mexico, 87131, USA Email: Larissa C Wilsie - [e-mail] ; Shree Chanchani - [e-mail]; Deepti Navaratna - [e-mail]; Robert A Orlando* - [e-mail] * Corresponding author

Published: 06 January 2005 Received: 10 November 2004 Lipids in Health and Disease 2005, 4 :2 doi:10.1186/1476-511X-4-2  Accepted: 06 January 2005 This article is available from: h ttp://www.lipidworld.com/content/4/1/2 © 2005 Wilsie et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited.

Abstract Background: Transport of fatty acids within the cyto sol of adipocytes and their subsequent assimilation into lipid dr oplets has been thoroughly investigat ed; however, the mechanism by which fatty acids are transported across the plasma membrane from the extracellular environment remains unclear. Since triacylglycero l-rich lipoproteins represent an abundant source of fatty acids for adipocyte utilization, we have investigated the expression levels of cell surface lipoprotein receptors and their functional co ntributions toward intracellular lipid accumulation; these include very low density lipoprot ein receptor (VLDL-R), lo w density lipoprotein re ceptor-related protein (LRP), and heparan sulfate proteoglycans (HSPG). Results: We found that expression of these three li poprotein receptors incr eased 5-fold, 2-fold, and 2.5-fold, respectively, during adipocyte diff erentiation. The major pr oteoglycans expressed by mature adipocytes are of high molecular we ight (>500 kD) and contain both heparan and chondroitin sulfate moieties. Using ligand binding antagonists, we observed that HSPG, rather than VLDL-R or LRP, play a primary role in the uptak e of DiI-lableled apoE-V LDL by mature adipocytes. In addition, inhibitors of HSPG ma turation resulted in a significan t reduction (>85%) in intracellular lipid accumulation. Conclusions: These results suggest that cell surface HS PG is required for fatty acid transport across the plasma membrane of adipocytes.

Background Fatty acids enter the adipocyte through the plasma mem- The adipocyte plays a central role in overall metabolic reg- brane, are converted to their acyl-CoA derivatives and ulation serving as a storage depot for fatty acids and as an transported through the cytosol with the assistance of endocrine cell to regulate energy utilization and feeding fatty acid binding proteins due to the lipophilic nature of behavior [1,2]. The mass of adipose tissue is maintained the fatty acid hydrocarbon chain [3,4]. They are then reas- by a well-controlled balance of cell proliferation (hyper- sembled into triacylglycerol units by acyltransferases. The plasia) and increase in fat cell size (hypertrophy). Con- intracellular lipid droplet that forms from the coalescence tributing to adipocyte hypertrophy is the assimilation of of triacylglycerols has recently been shown to associate fatty acids into cytosolic triacylglycerol-rich lipid droplets. with regulators of membrane trafficking in addition to

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