Endothelial Cell CD36 Optimizes Tissue Fatty Acid Uptake
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE116350 | GEO | 2018/06/28
REPOSITORIES: GEO
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Project description:Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examined how ECs transfer FAs. FA interaction with apical membrane CD36 induced Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Fission of the caveolae yielded vesicles containing FAs, CD36 and ceramide that were secreted basolaterally as small (80-100nm) exosome-like extracellular vesicles (sEVs). We visualized EC transfer of FAs in sEVs to underlying myotubes in transwells. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulated circulating FAs in emGFP-labeled puncta. The FA-sEV pathway was mapped through its suppression by CD36 depletion, blocking actin-remodeling, Src inhibition, Cav-1Y14 mutation, and neutral sphingomyelinase 2 inhibition. Suppression of sEV formation in mice reduced muscle FA uptake, raised circulating FAs, which remained in blood vessels, and lowered glucose, mimicking prominent Cd36-/- phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.
2023-07-02 | GSE235988 | GEO
Project description:Endothelial Cell CD36 Optimizes Tissue Fatty Acid Uptake
| PRJNA478230 | ENA
Project description:BACKGROUND & AIMS: The scavenger receptor CD36 has versatile immuno-metabolic actions. CD36 is abundantly expressed in the small intestinal epithelium but its impact on gut homeostasis is unknown. METHODS: Wild type (WT) and CD36-null (CD36KO) mice were fed a chow diet and small intestinal morphology assessed by immunohistochemistry and electron microscopy (EM). Inflammation was evaluated from neutrophil infiltration, expression of cytokines and toll-like receptors. Barrier integrity was determined using FITC-dextran and circulating lipopolysaccharide (LPS). Enterocyte (Ent-CD36KO) and endothelial (EC-CD36KO) CD36 null mice were generated to test contribution of epithelial versus endothelial CD36 to the intestinal phenotype. RESULTS: The small intestine of CD36KO mice fed a chow diet showed abnormal remodeling of the extracellular matrix (ECM) with altered expression of ECM and junction proteins. Hypertrophy of cell junctions and basement membranes was observed by EM. The CD36KO intestines displayed neutrophil infiltration, inflammation and compromised barrier function. Systemic leukocytosis and neutrophilia were present in CD36KO mice and there was 80% reduction of anti-inflammatory Ly6Clow monocytes important for ECM regulation and tissue repair. Bone marrow transplants supported primary contribution of tissue injury in initiation of inflammation. Studies with Ent-CD36KO mice did not support a major contribution of enterocyte CD36 while endothelial CD36 deficiency associated with neutrophil infiltration, aberrant expression of tight junctions and inflammation in the small intestine. CONCLUSION: CD36 is important for maintenance of barrier function in the small intestine. CD36 deletion causes ECM remodeling with collagen accumulation, depletion of the Ly6Clow monocyte subset and chronic inflammation. Endothelial but not enterocyte CD36 loss is a significant contributor to the spontaneous inflammation.
2016-10-01 | GSE73569 | GEO
Project description:Angiopoietin-like 4 (ANGPTL4) is known to regulate various cellular and systemic functions. However, its cell-specific role in endothelial cells (ECs) function and metabolic homeostasis remains to be elucidated. Here, using endothelial-specific Angptl4 knock-out mice (Angptl4iEC), and transcriptomics and metabolic flux analysis, we demonstrate that ANGPTL4 is required for maintaining EC metabolic function vital for vascular permeability and angiogenesis. Knockdown of ANGPTL4 in ECs promotes lipase-mediated lipoprotein lipolysis, which results in increased fatty acid (FA) uptake and oxidation. This is also paralleled by a decrease in proper glucose utilization for angiogenic activation of ECs. Mice with endothelial-specific deletion of Angptl4 showed decreased pathological neovascularization with stable vessel structures characterized by increased pericyte coverage and reduced permeability. Together, our study denotes the role of endothelial-ANGPTL4 in regulating cellular metabolism and angiogenic functions of EC.
2023-11-22 | GSE211128 | GEO
Project description:T cell metabolic fitness plays a pivotal role in anti-tumor immunity and metabolic deregulation causes T cell dysfunction in cancer. We identify that CD36 limits anti-tumor CD8+ T cell effector functions through lipid peroxidation. In murine tumors, oxidized phospholipids (OxPLs) were highly abundant and CD8+ TILs increased uptake and accumulation of lipids and lipid peroxidation. Functionally ‘exhausted’ CD8+ TILs increased CD36 expression and CD36-deficient CD8+ TILs had more robust anti-tumor activity and cytokine production than wild-type cells. We further show that CD36 promotes uptake of oxidized low-density lipoproteins (OxLDL), induces lipid peroxidation in CD8+ TILs, and enhances p38 kinase phosphorylation. Moreover, we found that OxLDL inhibits CD8+ T cell functions in a CD36/p38-dependent manner. Furthermore, glutathione peroxidase 4 (GPX4) over-expression lowers lipid peroxidation and restores functionalities in CD8+ TILs. These results define a key role for an oxidized lipid-CD36-p38 axis in promoting intratumoral CD8+ T cell dysfunction.
2021-03-31 | GSE171194 | GEO
Project description:Endothelial cells (ECs) act as an internal barrier to the vessel wall, hindering the development of inflammation, and only when activated will promote the development of vascular inflammation. However, the heterogeneity of the aortic ECs in the setting of vascular inflammation have not been fully assessed. Here, we defined 4 EC subpopulations, including Cd36+ EC, Notch3+ EC, Vcam1+ EC and Lyve1+ EC. Based on the enrichment analysis, Vcam1+ EC were considered to be a subpopulation of ECs susceptible to activation. After high-fat diet (HFD) intake, decreased expression of Krüppel-like factor 2 (Klf2) occurred only in Vcam1+ EC. Moreover, S1pr1 was validated as a downstream target protein of klf2. Upregulation of Klf2 expression ameliorated vascular ECs inflammation under HFD condition. Our study elucidates the Klf2 in Vcam1+ EC is a critical regulator of vascular inflammation and increases understanding of development and progression of aortic inflammatory disease.
2024-01-01 | GSE214014 | GEO
Project description:To identify markers preferentially expressed by capillary ECs (highly expressing CD36) in the disease-free human breast and gain insights into their biology, we used single cell RNA sequencing (scRNA-seq). For this analysis, dissociated cells from disease-free tissues were barcoded using the MULTI-seq protocol and pooled prior to FACS-based isolation of CD36+ and/or CD31+ cells. The droplet-based 10x Genomics Chromium platform was used to encapsulate single cells and construct cDNA libraries. Populations of fibroblasts, perivascular, lymphatic and vascular endothelial ECs where identified in this analysis.
2021-12-11 | GSE190592 | GEO
Project description:Limb expression 1-like protein (LIX1L) plays important role in various liver disorders, but its role and underlying mechanism in nonalcoholic hepatitis (NASH) and HCC progression remains obscure. Here, we report that LIX1L functions as a key integrative regulator linking lipid metabolism and inflammation, adipose tissue dysfunction and hepatic microenvironment reprogramming which promotes NASH progression. LIX1L significantly upregulated in NAFLD/NASH patients, mouse models and palmitic acid-stimulated hepatocytes. Lix1l deletion inhibits lipid deposition, inflammatory response and fibrosis in liver as well as adipocyte differentiation by downregulation of fatty acid translocase CD36 expression, alleviating NASH and associated HCC progression. In contrast, adeno-associated virus (AAV)-mediated LIX1L overexpression exacerbates NASH progression in mice. Mechanistically, metabolic stress promotes PARP1 mediated poly-ADP-ribosylation (PARylation) of LIX1L, subsequently increasing the stability and RNA binding ability of LIX1L protein. LIX1L binds to AU-rich element (ARE) in the 3’ untranslated region (UTR) of CD36 mRNA, thus attenuating CD36 mRNA decay. In NASH and associated HCC mouse models, LIX1L deficiency-mediated downregulation of CD36 suppresses adipogenesis, hepatic lipid uptake, and reprograms the tumor-prone liver microenvironment with increased cytotoxic T lymphocytes (CTLs), reduced immunosuppressive cell proportions. These data indicate a systematic function of LIX1L in the pathogenesis of NASH and underscore the PARP1/LIX1L/CD36 axis as a potential target for treatment of NASH and associated HCC.
2024-04-25 | GSE264479 | GEO
Project description:Adipose-derived MSCs (AMSC) are currently utilized in clinical trials for various diseases including osteoarthritis, amyotrophic lateral sclerosis, and multiple system atrophy. Whilst AMSCs may be defined by the surface expression of classical markers including CD44, CD90, CD105, and absence of CD45, these cells may exhbit donor-to-donor differences in differentiation potential. In this study we evaluated the expression of CD36 amongst AMSCs and utilized magnetic cell sorting to enrich for CD36+ cells. Whole transcriptome RNA-sequencing was performed on unsorted, CD36+ enriched, and CD36+ depleted cells to determine gene expression difference between these populations of cells. CD36 sorted or unsorted cells were then plated and maintained in growth medium. Cells were expanded for 2 passages and passage 8 cells were plated for RNA-sequencing analysis. Trizol reagent was used to harvest cells when they were proliferating cells (~80%) or 100% confluent cells.
2021-11-28 | GSE189525 | GEO