Fig. 3: Obesity triggers deregulation of metabolic and inflammatory networks in subsets of cardiac, lung, kidney and brain ECs.
a, UMAP clustering of cardiac ECs. b, Shifts in cardiac EC populations. Populations showing a log2 (WD/chow) > 0.3 change are highlighted in color. c, BioPlanet-annotated pathways upregulated in cardiac arterial ECs in obesity. The top 100 genes, ranked by fold change, were used for these analyses. d, Obesity-associated changes in the expression of AP1 transcription factor subunits. e, Obesity-associated gene expression changes in KLF-family transcription factors. f, UMAP clustering of lung ECs. g, Obesity-associated shifts in lung EC clusters. Populations showing a log2 (WD/chow) > 0.5 change are highlighted in color. h, FISH images showing overlap of typical pneumocyte markers (Lyz2, Sftpa1 and Sftpb) and EC marker (Pecam1). Double-positive cells are marked with arrows. Data were reproduced in three chow and three obese animals; scale bars, 5 µm. i, Changes in the expression of histocompatibility 2 (H2) genes in obesity. j, MSigDB-annotated pathways upregulated in aEC in obesity. The top 100 genes, ranked by fold change, were used for these analyses. k, UMAP clustering of kidney ECs; Ang, angiogenic. l, BioPlanet-annotated pathways upregulated in mEC2 cells in obesity. The top 100 genes, ranked by fold change, were used for these analyses; TCA, tricarboxylic acid. m, Top metabolic DEGs in mEC2 cells in obesity. n, Obesity-associated changes in the expression of AP1 transcription factor subunits. o, Quantification of DLK1 in gECs; n = 3 animals per group (black dots) and n = 10 images per animal (gray dots); scale bars, 20 µm. p, UMAP clustering of brain ECs. q, Obesity-associated changes in the expression of AP1 transcription factor subunits. r,s, Gene expression changes in select leukocyte adhesion (marked in red), tight junction (blue), adherens junction (green) and gap junction genes (black) in art (r) and fenestrated ECs (s) in obesity. t, Uptake of dextran dyes in the choroid plexus (CP); n = 5 animals per group (black dots); n = 4 sections per animal (gray dots); scale bars, 20 µm. Data in o and t are presented as mean ± s.e.m. and were analyzed using a two-sided Student’s t-test. The adjusted P value indicates adjustments for multiple comparisons using the Benjamini–Hochberg method (c, j and l).
