scholarly journals Fatty acid synthase promotes breast cancer metastasis by mediating changes in fatty acid metabolism

2020 ◽  
Vol 21 (1) ◽  
pp. 1-1
Author(s):  
Shuo Xu ◽  
Tingting Chen ◽  
Lihua Dong ◽  
Tao Li ◽  
Hui Xue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Cancer Metastasis ◽  
Acid Metabolism ◽  
Breast Cancer Metastasis

FC 102PD INDUCED ARTERIOLAR AND PERITONEAL PATHOMECHANISMS ARE PARTIALLY REVERSED AFTER KIDNEY TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Conghui Zhang ◽  
Maria Bartosova ◽  
Betti Schaefer ◽  
Rebecca Herzog ◽  
Rimante Cerkauskiene ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Parietal Peritoneum ◽  
Gene Set Enrichment Analysis ◽  
Biological Processes ◽  
Cell Counts

Abstract Background and Aims Due to the unphysiological composition of PD fluids, chronic peritoneal dialysis (PD) induces progressive peritoneal fibrosis, hypervascularization, and vasculopathy. The evolution of the PD membrane and vasculopathy following kidney transplantation (KTx) is largely unknown. Method Arteriolar and peritoneal tissues were obtained from 107 children with chronic kidney disease (CKD5), 72 children on PD (treated with neutral pH PD fluids, with low glucose degradation product content, GDP) and 21 children, who underwent KTx 4-5 weeks after a median 21 months of PD. Specimen underwent standardized digital quantitative histomorphometry. Molecular mechanisms were studied in omental arterioles microdissected from surrounding fat by multi-omics followed by Gene Set Enrichment Analysis (GSEA); key findings were validated in parietal tissues of independent, matched cohorts by quantitative immunohistochemistry (n=15/group). Results Arteriolar transcriptome and proteome GSEA revealed suppression of leucocyte migration and T-cell activation / secretory pathways regulation, of sprouting angiogenesis biological processes and of epithelial proliferation and cell cycle after KTx as compared to PD. Lipid / fatty acid metabolism, autophagy and ATP synthesis pathways were activated. Transcriptome analysis including KTx, PD and CKD5 specifically attributed regulation of arteriolar lipid and fatty acid metabolism to transplantation and comprised 140 transcripts; their regulation was confirmed on the proteome level. Hub gene fatty acid synthase was identified by protein interaction analysis (string-db.org). 15 arteriolar genes activated by PD were inactivated after KTx and included glucose metabolisms and cytoskeleton related transcripts. 24 transcripts and 10 corresponding proteins induced by PD were still active after KTx and associated with biological processes related to TGF-ß signaling, fibrosis and mineral absorption. In line with arteriolar multi-omics findings, peritoneal hypervascularization induced by chronic PD was reversed after Tx to CKD5 level. CD45 positive tissue infiltrating leucocytes count was reduced by 40% and was independently associated with microvessel density in multivariable analysis including PD vintage, daily GDP exposure and recent KTx. Peritoneal lymphatic vessel density, submesothelial thickness, activated fibroblast, fibrin deposit, macrophage and EMT cell counts remained unchanged after KTx compared to PD. Arteriolar lumen to vessel ratios (a marker of vasculopathy) were similar in both groups. Vessel-homeostasis-related proteins in independent, matched cohorts demonstrated increased caspase-3 abundance in peritoneal arterioles after KTx. Arteriolar VEGF-A, thrombospondin, angiopoietin1/2, and hypoxia-inducible factor-1 (HIF-1a) were unchanged, while submesothelial HIF-1a and angiopoietin1/2 were decreased after Tx, favoring vessel maturation. The abundance of the key driver of fibrosis, TGF-ß-effector pSMAD2/3, was unchanged in the peritoneum and arterioles after Tx. Conclusion Our multi-omics analyses of fat covered omental arterioles, not directly exposed to PD fluids, demonstrate inhibition of PD induced immune response and angiogenesis pathways, of glucose metabolism and cytoskeleton regulation to levels similar as seen in children with CKD5. Arteriolar lipid and fatty acid metabolism is selectively altered after KTx. Reversal of low GDP PD induced hypervascularization and inflammation of the parietal peritoneum after KTx, mirror molecular changes in omental arterioles, while profibrotic activity persists after KTx in omental arterioles and in the parietal peritoneum.

scholarly journals The effect of fetal pig size and stage of gestation on tissue fatty acid metabolism and profile

Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 757-763 ◽  
Author(s):  
Christopher J McNeil ◽  
Angela M Finch ◽  
Kenneth R Page ◽  
Steve D Clarke ◽  
Cheryl J Ashworth ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fetal Growth ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthase ◽  
Porcine Model ◽  
Acid Metabolism ◽  
Fatty Acid Status ◽  
Δ5 Desaturase ◽  
Acid Status ◽  
Δ6 Desaturase

The fetus requires an adequate supply of fatty acids for optimum growth and development. It has been hypothesized that reduced activity of enzymes of fatty acid metabolism could contribute to inadequate fetal growth. In a porcine model of differential fetal growth we examined heart and liver fatty acid synthase, Δ5-desaturase and Δ6-desaturase gene expression and measured hepatic fatty acid profile to assess long-chain polyunsaturated fatty acid status. On gestation days 45, 65 and 100 sows were killed and tissues extracted from an average-sized fetus and the smallest fetus from each litter. As early as day 45, considerable hepatic Δ5- and Δ6-desaturase was detected, and this expression significantly increased as gestation progressed. In contrast, cardiac desaturase expression remained stable with time. Fatty acid synthase expression was greatest at day 65 in the liver, but was not expressed in the heart. Overall, the smallest fetus did not exhibit reduced tissue Δ5- or Δ6-desaturase expression or compromised polyunsaturated fatty acid status at any stage. In fact, small fetuses expressed more cardiac Δ5-desaturase than their average-sized siblings, possibly in response to a stress to the heart. It is clear from this study that fatty acid metabolism changes markedly as gestation progresses, and reduced fatty acid supply does not cause inadequate growth in this porcine model of fetal development.

Fatty acid metabolism in breast cancer cells: differential inhibitory effects of epigallocatechin gallate (EGCG) and C75

2007 ◽  
Vol 109 (3) ◽  
pp. 471-479 ◽  
Author(s):  
Teresa Puig ◽  
Alejandro Vázquez-Martín ◽  
Joana Relat ◽  
Jordi Pétriz ◽  
Javier A. Menéndez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Metabolism ◽  
Breast Cancer Cells ◽  
Acid Metabolism ◽  
Epigallocatechin Gallate ◽  
Inhibitory Effects

scholarly journals Cathepsin Inhibition Modulates Metabolism and Polarization of Tumor-Associated Macrophages

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2579
Author(s):  
Diana Oelschlaegel ◽  
Tommy Weiss Sadan ◽  
Seth Salpeter ◽  
Sebastian Krug ◽  
Galia Blum ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Immune Cells ◽  
Fatty Acid Synthase ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Marker Genes ◽  
Tumor Associated Macrophages ◽  
Cathepsin Activity ◽  
The Impact

Stroma-infiltrating immune cells, such as tumor-associated macrophages (TAM), play an important role in regulating tumor progression and chemoresistance. These effects are mostly conveyed by secreted mediators, among them several cathepsin proteases. In addition, increasing evidence suggests that stroma-infiltrating immune cells are able to induce profound metabolic changes within the tumor microenvironment. In this study, we aimed to characterize the impact of cathepsins in maintaining the TAM phenotype in more detail. For this purpose, we investigated the molecular effects of pharmacological cathepsin inhibition on the viability and polarization of human primary macrophages as well as its metabolic consequences. Pharmacological inhibition of cathepsins B, L, and S using a novel inhibitor, GB111-NH2, led to changes in cellular recycling processes characterized by an increased expression of autophagy- and lysosome-associated marker genes and reduced adenosine triphosphate (ATP) content. Decreased cathepsin activity in primary macrophages further led to distinct changes in fatty acid metabolites associated with increased expression of key modulators of fatty acid metabolism, such as fatty acid synthase (FASN) and acid ceramidase (ASAH1). The altered fatty acid profile was associated with an increased synthesis of the pro-inflammatory prostaglandin PGE2, which correlated with the upregulation of numerous NFkB-dependent pro-inflammatory mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor-alpha (TNFα). Our data indicate a novel link between cathepsin activity and metabolic reprogramming in macrophages, demonstrated by a profound impact on autophagy and fatty acid metabolism, which facilitates a pro-inflammatory micromilieu generally associated with enhanced tumor elimination. These results provide a strong rationale for therapeutic cathepsin inhibition to overcome the tumor-promoting effects of the immune-evasive tumor micromilieu.

scholarly journals Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

2018 ◽  
Vol 12 (9) ◽  
pp. 1623-1638 ◽  
Author(s):  
Seher Balaban ◽  
Lisa S. Lee ◽  
Bianca Varney ◽  
Atqiya Aishah ◽  
Quanqing Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Metabolism ◽  
Breast Cancer Cells ◽  
Acid Metabolism ◽  
Differential Sensitivity ◽  
Induced Apoptosis
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