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Abstract

BackgroundTransport 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).ResultsWe 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.ConclusionsThese results suggest that cell surface HSPG is required for fatty acid transport across the plasma membrane of adipocytes.

Apolipoprotein E2 Accentuates Postprandial Inflammation and Diet-Induced Obesity to Promote Hyperinsulinemia in Mice

“…Typically, lipids from triglyceride-rich lipoproteins are taken up by leukocytes and adipocytes through two distinct mechanisms, one involving lipoprotein lipase–mediated hydrolysis of the triglycerides followed by the uptake of the liberated fatty acids (33,34) and another via whole lipoprotein particle endocytosis after binding to LDL receptor–related protein-1 (LRP1), VLDL receptor, and/or heparin sulfate proteoglycans (HSPGs) (27,35,36). Previous studies have shown that apoE2-containing lipoproteins are poor substrates for lipoprotein lipase in comparison with apoE3 lipoproteins (37).…”

Adipocyte extracellular matrix composition, dynamics and role in obesity

“…Wilsie et al [49] detected a clear influence of HSPGs on lipid uptake in 3T3-L1 adipocytes. They propose a model in which HSPG serves as a binding site for lipid particles (apoE-VLDL).…”

Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis

“…6 Both adipogenesis and lipogenesis are stimulated by insulin which increases adipocyte cell size 7 through transcriptional inhibition of apoptosis and activation of lipid droplet synthesis 8 but also controls the transcription and/or secretion of numerous secreted factors such as adiponectin. 9 Lipid uptake by adipocytes is performed through interaction with intracellular fatty acid binding proteins FABP1 and FABP4, with fatty acid translocase FAT/CD36, lipoprotein receptor heparan sulfate proteoglycans HSPG but also G-protein coupled receptors, then accumulation as triglycerides in lipid droplets, [10][11][12][13][14][15][16][17][18] however their respective functions in fatty acid storage and intracellular signaling need further investigations.…”