Human adipose tissue microvascular endothelial cells secrete PPARγ ligands and regulate adipose tissue lipid uptake
Silvia Gogg, Annika Nerstedt, Jan Boren, Ulf Smith
Silvia Gogg, Annika Nerstedt, Jan Boren, Ulf Smith
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Research Article Cell biology

Human adipose tissue microvascular endothelial cells secrete PPARγ ligands and regulate adipose tissue lipid uptake

Abstract

Human adipose cells cannot secrete endogenous PPARγ ligands and are dependent on unknown exogenous sources. We postulated that the adipose tissue microvascular endothelial cells (aMVECs) cross-talk with the adipose cells for fatty acid (FA) transport and storage and also may secrete PPARγ ligands. We isolated aMVECs from human subcutaneous adipose tissue and showed that in these cells, but not in (pre)adipocytes from the same donors, exogenous FAs increased cellular PPARγ activation and markedly increased FA transport and the transporters FABP4 and CD36. Importantly, aMVECs only accumulated small lipid droplets and could not be differentiated to adipose cells and are not adipose precursor cells. FA exchange between aMVECs and adipose cells was bidirectional, and FA-induced PPARγ activation in aMVECs was dependent on functional adipose triglyceride lipase (ATGL) protein while deleting hormone-sensitive lipase in aMVECs had no effect. aMVECs also released lipids to the medium, which activated PPARγ in reporter cells as well as in adipose cells in coculture experiments, and this positive cross-talk was also dependent on functional ATGL in aMVECs. In sum, aMVECs are highly specialized endothelial cells, cannot be differentiated to adipose cells, are adapted to regulating lipid transport and secreting lipids that activate PPARγ, and thus, regulate adipose cell function.

Authors

Silvia Gogg, Annika Nerstedt, Jan Boren, Ulf Smith

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Figure 7

Suppressive effect of ATGL siRNA.

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Suppressive effect of ATGL siRNA. aMVECs were transfected with siC or sm...
aMVECs were transfected with siC or small interfering ATGL (siATGL). Twenty-four hours after transfection, medium was changed to stimulation medium without (BAS) or with 300 μM OA or 100 μM GW9508 and incubated for an additional 24 hours. (A–D) Western blots were performed using antibodies specific for ATGL, FABP4, CD36, PPARγ, and actin was used as a loading control. Protein levels were analyzed by densitometry, and the bar histograms show protein levels of respective proteins normalized to actin from at least 5 experiments. (E) The figure shows representative Western blots of CD36, ATGL, PPARγ, actin, and FABP4 in cells transfected with siC (left) or with siATGL (right). (F) Microphotographs of aMVECs transfected with RNA interference as described. Cells were treated without (BAS) or with 200 μM OA. The presence of lipids was revealed by Oil Red O staining (original magnification, ×100). (G–I) Western blots were performed as above, and data were obtained from at least 6 experiments. (J) Representative Western blots from the same membrane of CD36, ATGL, actin, and FABP4 for cells transfected with siC (left) or with siATGL (right). Vertical lines represent removed and rejoined data from the same Western blot membranes. Bars represent mean ± SEM. Wilcoxon’s signed-rank test; *P < 0.05; **P < 0.01.