Cell surface heparan sulfate proteoglycans contribute to intracellular lipid accumulation in adipocytes.
BACKGROUND
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-labeled 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.
Wilsie
Larissa C
LC
Department of Biochemistry and Molecular Biology, University of New Mexico, Health Sciences Center, 915 Camino de Salud, Albuquerque, New Mexico 87131, USA. lcwilsie@salud.unm.edu
Chanchani
Shree
S
Navaratna
Deepti
D
Orlando
Robert A
RA
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D005786:Gene Expression Regulation; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008970:Molecular Weight; D011973:Receptors, LDL / Q000378:metabolism
D001057:Apolipoproteins E; D019812:Heparan Sulfate Proteoglycans; D026502:LDL-Receptor Related Proteins; D011973:Receptors, LDL; C036053:VLDL receptor