scholarly journals Metabolic Reprogramming from Glycolysis to Fatty Acid Uptake and beta-Oxidation in Platinum-Resistant Cancer Cells

2021 ◽  
Author(s):  
Junjie Li ◽  
Yuying Tan ◽  
Guangyuan Zhao ◽  
Kai-Chih Huang ◽  
Horacio Cardenas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Single Cell ◽  
Cancer Cell ◽  
Aerobic Glycolysis ◽  
Fatty Acid Uptake ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Acid Uptake ◽  
Beta Oxidation

Increased aerobic glycolysis is widely considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during development of therapeutic resistance is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we found that cisplatin-resistant cells exhibit increased uptake of exogenous fatty acids, accompanied with decreased glucose uptake and de novo lipogenesis, indicating a reprogramming from glucose and glycolysis dependent to fatty acid uptake and beta-oxidation dependent anabolic and energy metabolism. A metabolic index incorporating measurements of glucose derived anabolism and fatty acid uptake correlates linearly to the level of resistance to cisplatin in ovarian cancer cell lines and in primary cells isolated from ovarian cancer patients. Mechanistically, the increased fatty acid uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing energy production through beta-oxidation. Consequently, blocking fatty acid beta-oxidation by a small molecule inhibitor in combination with cisplatin or carboplatin synergistically suppressed ovarian cancer proliferation in vitro and growth of patient-derived xenograft in vivo. Collectively, these findings support a new way for rapid detection of cisplatin-resistance at single cell level and a new strategy for treatment of cisplatin-resistant tumors.

scholarly journals Angiopoietin-Like 4 Mediates PPAR Delta Effect on Lipoprotein Lipase-Dependent Fatty Acid Uptake but Not on Beta-Oxidation in Myotubes

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46212 ◽  
Author(s):  
Marius R. Robciuc ◽  
Paulina Skrobuk ◽  
Andrey Anisimov ◽  
Vesa M. Olkkonen ◽  
Kari Alitalo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipoprotein Lipase ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Beta Oxidation ◽  
Ppar Delta

IL-17A promotes fatty acid uptake through the IL-17A/IL-17RA/p-STAT3/FABP4 axis to fuel ovarian cancer growth in an adipocyte-rich microenvironment

2019 ◽  
Vol 69 (1) ◽  
pp. 115-126 ◽  
Author(s):  
Chunyan Yu ◽  
Xiulong Niu ◽  
Yongrui Du ◽  
Yan Chen ◽  
Xiaomei Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Cancer Growth ◽  
Acid Uptake

scholarly journals L-FABP and I-FABP expression increase NBD-stearate uptake and cytoplasmic diffusion in L cells

1998 ◽  
Vol 275 (2) ◽  
pp. G244-G249 ◽  
Author(s):  
Eric J. Murphy
Keyword(s):  
Fatty Acid ◽  
Single Cell ◽  
Lipid Droplets ◽  
Fatty Acid Binding Protein ◽  
Diffusion Rate ◽  
Single Cells ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Intact Cells ◽  
Fatty Acid Binding

The effects of intestinal and liver fatty acid binding protein (I- and L-FABP, respectively) expression on single-cell fatty acid uptake, internalization, and cytoplasmic diffusion were determined in transfected L cell fibroblasts. These parameters were measured using the nonesterifiable fluorescent fatty acid probe 12- N-methyl-(7-nitrobenz-2-oxa-1,3-diazol)aminostearate (NBD-stearate) and fluorescence digital imaging. In single-cell fluorescence imaging experiments, L-FABP-expressing cells, but not I-FABP-expressing cells, increased NBD-stearate uptake 1.7-fold compared with control cells. Both I- and L-FABP increased the cytoplasmic diffusion rate of the internalized NBD-stearate 2.6- and 1.9-fold, respectively, compared with control cells. However, increased NBD-stearate lateral membrane mobility was observed only in L-FABP-expressing cells. After incubation of the cells with 4 μM NBD-stearate at 37°C for 30 min, fluorescence deconvolution imaging indicated that NBD-stearate was localized primarily into lipid droplets in all cell lines. The differential effect of these proteins on fatty acid uptake and intracellular trafficking in single cells illustrates a possible difference in the physiological function of I- and L-FABP in intact cells.

scholarly journals FADS2-mediated fatty acid desaturation and cholesterol esterification are signatures of metabolic reprogramming during melanoma progression

2020 ◽  
Author(s):  
Hyeon Jeong Lee ◽  
Zhicong Chen ◽  
Marianne Collard ◽  
Jiaji G Chen ◽  
Muzhou Wu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Metastatic Melanoma ◽  
Therapeutic Potential ◽  
Fatty Acid Uptake ◽  
Melanoma Cells ◽  
Metabolic Reprogramming ◽  
Cholesterol Esterification ◽  
Low Grade ◽  
Acid Uptake ◽  
Melanoma Progression

AbstractIdentifying metabolic alterations in disease progression has been challenged by difficulties in tracking metabolites at sub-cellular level. Here, by high-resolution stimulated Raman scattering and pump-probe imaging and spectral phasor analysis of melanoma cells grouped by MITF/AXL expression pattern and of human patient tissues paired by primary and metastatic status, we identify a metabolic switch from a pigment-containing phenotype in low-grade melanoma to a lipid-rich phenotype in metastatic melanoma. The lipids found in MITFlow/AXLhigh melanoma cells contain high levels of cholesteryl ester (CE) and unsaturated fatty acid species. Elevated fatty acid uptake activity in MITFlow/AXLhigh melanoma contributes to the lipid-rich phenotype, and inhibiting fatty acid uptake suppresses cell migration. Importantly, monounsaturated sapienate is identified as an essential fatty acid that effectively promotes cancer migration. Blocking either FADS2-mediated lipid desaturation or SOAT-mediated cholesterol esterification effectively suppresses the migration capacity of melanoma in vitro and in vivo, indicating the therapeutic potential of targeting these metabolic pathways in metastatic melanoma. Collectively, our results reveal metabolic reprogramming during melanoma progression, and highlight metabolic signatures that could serve as targets for metastatic melanoma treatment and diagnosis.

Single-Cell Profiling of Fatty Acid Uptake Using Surface-Immobilized Dendrimers

2021 ◽  
Author(s):  
Zhili Guo ◽  
Hanjun Cheng ◽  
Zhonghan Li ◽  
Shiqun Shao ◽  
Priyanka Sarkar ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Single Cell ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Single Cell Profiling

Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer

2019 ◽  
Vol 11 (478) ◽  
pp. eaau5758 ◽  
Author(s):  
Matthew J. Watt ◽  
Ashlee K. Clark ◽  
Luke A. Selth ◽  
Vanessa R. Haynes ◽  
Natalie Lister ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
De Novo ◽  
Human Cancer ◽  
Critical Role ◽  
Fatty Acid Uptake ◽  
De Novo Lipogenesis ◽  
Therapeutic Effects ◽  
Acid Uptake

Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer and that these fatty acids were directed toward biomass production. These changes were mediated, at least partly, by the fatty acid transporter CD36, which was associated with aggressive disease. Deleting Cd36 in the prostate of cancer-susceptible Pten−/− mice reduced fatty acid uptake and the abundance of oncogenic signaling lipids and slowed cancer progression. Moreover, CD36 antibody therapy reduced cancer severity in patient-derived xenografts. We further demonstrated cross-talk between fatty acid uptake and de novo lipogenesis and found that dual targeting of these pathways more potently inhibited proliferation of human cancer-derived organoids compared to the single treatments. These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer.

Fatty acid and glucose utilization in isolated, working fetal pig hearts

1983 ◽  
Vol 245 (1) ◽  
pp. E19-E23 ◽  
Author(s):  
J. C. Werner ◽  
V. Whitman ◽  
R. R. Fripp ◽  
H. G. Schuler ◽  
J. Musselman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Glucose Utilization ◽  
Short Chain Fatty Acids ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Beta Oxidation ◽  
Tissue Concentrations ◽  
Long Chain ◽  
Fetal Pig

Fatty acid uptake and the effects of long- and short-chain fatty acids on glucose utilization were assessed in isolated perfused fetal pig hearts (0.9 gestation) in which oxygenated nutrient buffer was pumped from both ventricles at controlled pressure (55 mmHg, mean arterial pressure) and heart rate (180 beats/min). When either 1.5 mM palmitate or 1.0 mM octanoate was added to buffer containing 10 mM glucose and insulin (100 microU/ml), glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed when compared with glucose uptake in the absence of fatty acid. Increased tissue concentrations of glucose 6-phosphate, fructose 6-phosphate, and citrate in hearts perfused with buffer containing octanoate indicated active beta-oxidation and inhibition of phosphofructokinase activity when compared with hearts perfused with glucose alone. In contrast, hearts perfused with buffer containing palmitate showed no increases in these metabolic intermediates. These results suggest that suppression of glucose uptake in the presence of long-chain fatty acid was not the result of phosphofructokinase inhibition but may result from inhibition of glucose transport by palmitate. Determinations of tissue concentrations of free carnitine and carnitine derivatives indicated that, although palmitate underwent esterification to long-chain acyl carnitine in the fetal heart, it failed to undergo extensive beta-oxidation.

scholarly journals Multimodal Metabolic Imaging Reveals Pigment Reduction and Lipid Accumulation in Metastatic Melanoma

BME Frontiers ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Hyeon Jeong Lee ◽  
Zhicong Chen ◽  
Marianne Collard ◽  
Fukai Chen ◽  
Jiaji G. Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Early Diagnosis ◽  
Metastatic Melanoma ◽  
Lipid Accumulation ◽  
Fatty Acid Uptake ◽  
Metabolic Reprogramming ◽  
Low Grade ◽  
Acid Uptake ◽  
Subcellular Level ◽  
Metabolic Signatures

Objective and Impact Statement. Molecular signatures are needed for early diagnosis and improved treatment of metastatic melanoma. By high-resolution multimodal chemical imaging of human melanoma samples, we identify a metabolic reprogramming from pigmentation to lipid droplet (LD) accumulation in metastatic melanoma. Introduction. Metabolic plasticity promotes cancer survival and metastasis, which promises to serve as a prognostic marker and/or therapeutic target. However, identifying metabolic alterations has been challenged by difficulties in mapping localized metabolites with high spatial resolution. Methods. We developed a multimodal stimulated Raman scattering and pump-probe imaging platform. By time-domain measurement and phasor analysis, our platform allows simultaneous mapping of lipids and pigments at a subcellular level. Furthermore, we identify the sources of these metabolic signatures by tracking deuterium metabolites at a subcellular level. By validation with mass spectrometry, a specific fatty acid desaturase pathway was identified. Results. We identified metabolic reprogramming from a pigment-containing phenotype in low-grade melanoma to an LD-rich phenotype in metastatic melanoma. The LDs contain high levels of cholesteryl ester and unsaturated fatty acids. Elevated fatty acid uptake, but not de novo lipogenesis, contributes to the LD-rich phenotype. Monounsaturated sapienate, mediated by FADS2, is identified as an essential fatty acid that promotes cancer migration. Blocking such metabolic signatures effectively suppresses the migration capacity both in vitro and in vivo. Conclusion. By multimodal spectroscopic imaging and lipidomic analysis, the current study reveals lipid accumulation, mediated by fatty acid uptake, as a metabolic signature that can be harnessed for early diagnosis and improved treatment of metastatic melanoma.

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