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
View: Text | PDF
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

×

Figure 4

Effect of OA in PAs.

Options: View larger image (or click on image) Download as PowerPoint
Effect of OA in PAs. (A–C) Human PAs were starved and incubated without ...
(A–C) Human PAs were starved and incubated without (BAS) or with 300 μM OA or 5 μM ROSI for 24 hours. qRT-PCR of FABP4 (A), CD36 (B), and PPARγ (C); n = 6. *P < 0.05; **P < 0.01 compared with BAS. (D–F) aMVECs and PAs cross-talk. aMVECs and PAs were grown independently either in cell culture dishes or in cell culture inserts for 48 hours. PAs were cocultured with the aMVEC insert or without (BAS) for an additional 48 hours. qRT-PCR of FABP4, where n = 8 (D), and PPARγ, where n = 6 (E). *P < 0.05. (F) Correlation between PPARγ expression and donor’s BMI; n = 6, and P < 0.05. Pearson’s correlation. (G and H) PPARγ activation: PPARγ-UAS-bla HEK 293H cells were plated in a 384-well plate and cultured for 20 hours with aMVEC- or PA-conditioned medium obtained after 24 hours of incubation. Naive medium was used as a control. After the incubation time the assay was resolved as described in Methods, and the fluorescence emission values at 460 nm (blue) and 530 nm (green) were obtained after 90 minutes using a fluorescence plate reader. (G) The bars show the blue/green ratio after background subtraction (medium only, without cells) for each condition tested; n = 6. *P < 0.05; **P < 0.01 compared with naive medium; #P < 0.05 compared with BAS aMVECs. (H) Dose-response of PPARγ-UAS-bla HEK 293H cells exposed to ROSI and resolved with the same assay (n = 4). Bars represent mean ± SEM. Kruskal-Wallis test (A–C and G) and Wilcoxon’s signed-rank test (D and E).