scholarly journals Characterization of Lipid and Lipid Droplet Metabolism in Human HCC

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 512 ◽  
Author(s):  
Nikolaus Berndt ◽  
Johannes Eckstein ◽  
Niklas Heucke ◽  
Robert Gajowski ◽  
Martin Stockmann ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Expression Profiles ◽  
Primary Liver Cancer ◽  
Fatty Acid Uptake ◽  
Metabolic Phenotype ◽  
Acid Uptake ◽  
Specific Expression ◽  
Very High

Human hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with cirrhosis. While previous metabolic studies of HCC have mainly focused on the glucose metabolism (Warburg effect), less attention has been paid to tumor-specific features of the lipid metabolism. Here, we applied a computational approach to analyze major pathways of fatty acid utilization in individual HCC. To this end, we used protein intensity profiles of eleven human HCCs to parameterize tumor-specific kinetic models of cellular lipid metabolism including formation, enlargement, and degradation of lipid droplets (LDs). Our analysis reveals significant inter-tumor differences in the lipid metabolism. The majority of HCCs show a reduced uptake of fatty acids and decreased rate of β-oxidation, however, some HCCs display a completely different metabolic phenotype characterized by high rates of β-oxidation. Despite reduced fatty acid uptake in the majority of HCCs, the content of triacylglycerol is significantly enlarged compared to the tumor-adjacent tissue. This is due to tumor-specific expression profiles of regulatory proteins decorating the surface of LDs and controlling their turnover. Our simulations suggest that HCCs characterized by a very high content of triglycerides comprise regulatory peculiarities that render them susceptible to selective drug targeting without affecting healthy tissue.

scholarly journals The effect of high glucose on lipid metabolism in the human placenta

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Charlotte H. Hulme ◽  
Anna Nicolaou ◽  
Sharon A. Murphy ◽  
Alexander E. P. Heazell ◽  
Jenny E. Myers ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
High Glucose ◽  
Fatty Acid Uptake ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Obese Women ◽  
Lipid Transfer ◽  
Glucose Levels ◽  
Fatty Acid Transport Proteins

Abstract Diabetes mellitus (DM) during pregnancy can result in fetal overgrowth, likely due to placental dysfunction, which has health consequences for the infant. Here we test our prediction from previous work using a placental cell line that high glucose concentrations affect placental lipid metabolism. Placentas from women with type 1 (n = 13), type 2 (n = 6) or gestational (n = 12) DM, BMI-matched to mothers without DM (n = 18), were analysed for lipase and fatty acid transport proteins and fatty acid and triglyceride content. Explants from uncomplicated pregnancies (n = 6) cultured in physiological or high glucose were similarly analysed. High glucose levels did not alter placental lipase or transporter expression or the profile and abundance of fatty acids, but triglyceride levels were higher (p < 0.05), suggesting reduced β- oxidation. DM did not affect placental protein expression or fatty acid profile. Triglyceride levels of placentas from mothers with pre-existing DM were similar to controls, but higher in obese women with gestational DM. Maternal hyperglycemia may not affect placental fatty acid uptake and transport. However, placental β-oxidation is affected by high glucose and reduced in a subset of women with DM. Abnormal placental lipid metabolism could contribute to increased maternal-fetal lipid transfer and excess fetal growth in some DM pregnancies.

scholarly journals Temozolomide Treatment Increases Fatty Acid Uptake in Glioblastoma Stem Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3126
Author(s):  
Seamus Caragher ◽  
Jason Miska ◽  
Jack Shireman ◽  
Cheol H. Park ◽  
Megan Muroski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Current Treatment ◽  
Metabolic Phenotype ◽  
Treatment Modalities ◽  
Environmental Cues ◽  
Acid Uptake ◽  
Current Standard ◽  
Cell State

Among all cancers, glioblastoma (GBM) remains one of the least treatable. One key factor in this resistance is a subpopulation of tumor cells termed glioma stem cells (GSCs). These cells are highly resistant to current treatment modalities, possess marked self-renewal capacity, and are considered key drivers of tumor recurrence. Further complicating an understanding of GBM, evidence shows that the GSC population is not a pre-ordained and static group of cells but also includes previously differentiated GBM cells that have attained a GSC state secondary to environmental cues. The metabolic behavior of GBM cells undergoing plasticity remains incompletely understood. To that end, we probed the connection between GSCs, environmental cues, and metabolism. Using patient-derived xenograft cells, mouse models, transcriptomics, and metabolic analyses, we found that cell state changes are accompanied by sharp changes in metabolic phenotype. Further, treatment with temozolomide, the current standard of care drug for GBM, altered the metabolism of GBM cells and increased fatty acid uptake both in vitro and in vivo in the plasticity driven GSC population. These results indicate that temozolomide-induced changes in cell state are accompanied by metabolic shifts—a potentially novel target for enhancing the effectiveness of current treatment modalities.

scholarly journals Lipid metabolism in women

2004 ◽  
Vol 63 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Christine M. Williams
Keyword(s):  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Body Fat ◽  
Adrenergic Receptors ◽  
Subcutaneous Fat ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Fat Depots

Differences in whole-body lipid metabolism between men and women are indicated by lower-body fat accumulation in women but more marked accumulation of fat in the intra-abdominal visceral fat depots of men. Circulating blood lipid concentrations also show gender-related differences. These differences are most marked in premenopausal women, in whom total cholesterol, LDL-cholesterol and triacylglycerol concentrations are lower and HDL-cholesterol concentration is higher than in men. Tendency to accumulate body fat in intra-abdominal fat stores is linked to increased risk of CVD, metabolic syndrome, diabetes and other insulin-resistant states. Differential regional regulation of adipose tissue lipolysis and lipogenesis must underlie gender-related differences in the tendency to accumulate fat in specific fat depots. However, empirical data to support current hypotheses remain limited at the present time because of the demanding and specialist nature of the methods used to study adipose tissue metabolism in human subjects. In vitro and in vivo data show greater lipolytic sensitivity of abdominal subcutaneous fat and lesser lipolytic sensitivity of femoral and gluteal subcutaneous fat in women than in men. These differences appear to be due to fewer inhibitory α adrenergic receptors in abdominal regions and greater α adrenergic receptors in gluteal and femoral regions in women than in men. There do not appear to be major gender-related differences in rates of fatty acid uptake (lipogenesis) in different subcutaneous adipose tissue regions. In visceral fat rates of both lipolysis and lipogenesis appear to be greater in men than in women; higher rates of lipolysis may be due to fewer α adrenergic receptors in this fat depot in men. Fatty acid uptake into this depot in the postprandial period is approximately 7-fold higher in men than in women. Triacylglycerol concentrations appear to be a stronger cardiovascular risk factor in women than in men, with particular implications for cardiovascular risk in diabetic women. The increased triacylglycerol concentrations observed in women taking hormone-replacement therapy (HRT) may explain the paradoxical findings of increased rates of CVD in women taking HRT that have been reported from recent primary and secondary prevention trials of HRT.

scholarly journals AB0028 EXPRESSION OF FATTY ACID TRANSPORTERS AND FREE FATTY ACID UPTAKE IN CD8+ T CELLS IN AUTOIMMUNE ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1047.2-1048
Author(s):  
S. Keck ◽  
F. V. Kraus ◽  
H. M. Lorenz ◽  
M. Souto-Carneiro
Keyword(s):  
T Cells ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Free Fatty Acid ◽  
Disease Activity ◽  
Cd8 T Cells ◽  
Disease Duration ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Effector Functions

Background:RA CD8+ T cells (CD8s) have been shown to vastly contribute to tissue damage and RA disease activity by presenting and maintaining an active effector phenotype promoting autoinflammation. In order to meet their high metabolic requirements RA CD8s alter not only their glycolytic and glutaminolytic profiles, but also rely on increased lipid metabolism characterized by increased free fatty acid (FFA) uptake and lipid biosynthesis.Objectives:In order to classify the importance of lipid metabolism in RA CD8s in terms of initiation and perpetuation of effector functions and therefore exploring potential novel therapy targeting points or biomarkers additional investigations have to been made. By analysing FFA uptake and the expression of free fatty acid transporters (FAT) upon TCR-stimulation in RA, PsA, SpA patients and healthy controls (HC), we aimed to further characterize the importance of RA CD8s´ lipid metabolism.Methods:Blood samples from 23 RA patients, 22 SpA patients, 20 PsA patients and 7 HC recruited at Heidelberg University Hospital were processed via negative magnetic separation selection to obtain purified CD8s. CD8s were cultured for 72 hours in [1,6-13C] glucose containing medium in the presence of anti-CD3 and anti-CD28. FFA uptake was measured by Palmitate-Bodipy 488 staining (ThermoFisher), the expression of FAT CD36, FABP4 and GPR84 besides CD69, CD36, CD45RA, CD3 and CD8 were assessed by FACS analysis.Ethic approval NR: S-096/2016.Results:The intake of the FFA palmitate by CD8s was higher in all patients groups than in HC (p < 0,05). In all three diseases´ stimulated CD8s, unlike in the HC group, the expression of GPR84 was inversely correlating to the expression of CD69 (Spearman r < -0,62). In patient´s stimulated CD8s the expression of GPR84 tended to be lower in RA and PSA effector memory (EM) CD8s. In RA and HC the expression of FABP4 tended to be lower in the naive CD8+ subset when compared to the effector subset. HC naive and effector CD8+ subsets had a higher expression of CD36 than in the patient groups. In RA and SPA patients the expression of FAT correlated with clinical variables. In RA DAS28 and CRP inversely correlated with CD36 (MFI), and disease duration with FABP4 as well. In SPA CRP and BASDAI inversely correlated with FABP4 while disease duration had a negative correlation with CD36 (MFI). GPR84 (MFI) had an inverted relationship to BASDAI. While the BMI was directly correlated with the expression of CD36 in RA, this relationship was inverted in SPA.Conclusion:A high free fatty acid uptake seems to characterize autoimmune arthritis CD8+ T cells. The gain of effector functions appears to be connected to changes in the expression of different fatty acid transporters on the surface of CD8+ T cells. The correlation between the expression of fatty acid transporters and clinical parameters (specially disease activity scores) in RA and SPA suggests that they could potentially be used as biomarkers for disease activity and progression.Acknowledgements:We thank all the individuals involved in the study for their participation.Disclosure of Interests:None declared

scholarly journals Identification and characterization of inhibitors of hsFATP‐dependent fatty acid uptake in humanized yeast and human Caco‐2 cells

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Angel Sandoval‐Alvarez ◽  
Aalap Chokshi ◽  
Diane Singer ◽  
Paul N. Black ◽  
Concetta C. DiRusso
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Identification And Characterization

Characterization of Membrane Transport Processes: Lessons from the Study of BSP, Bilirubin, and Fatty Acid Uptake

1996 ◽  
Vol 16 (02) ◽  
pp. 107-120 ◽  
Author(s):  
Paul Berk ◽  
Michael Bradbury ◽  
Sheng-Li Zhou ◽  
Decherd Stump ◽  
Nam-Ik Han
Keyword(s):  
Fatty Acid ◽  
Membrane Transport ◽  
Fatty Acid Uptake ◽  
Transport Processes ◽  
Acid Uptake

scholarly journals Toward Quantitative in vivo Label-Free Tracking of Lipid Distribution in a Zebrafish Cancer Model

2021 ◽  
Vol 9 ◽  
Author(s):  
Marco Andreana ◽  
Caterina Sturtzel ◽  
Clemens P. Spielvogel ◽  
Laszlo Papp ◽  
Rainer Leitgeb ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Lipid Accumulation ◽  
Fatty Acid Uptake ◽  
Alternative Mechanism ◽  
Acid Uptake ◽  
Label Free ◽  
Tumor Onset

Cancer cells often adapt their lipid metabolism to accommodate the increased fatty acid demand for membrane biogenesis and energy production. Upregulation of fatty acid uptake from the environment of cancer cells has also been reported as an alternative mechanism. To investigate the role of lipids in tumor onset and progression and to identify potential diagnostic biomarkers, lipids are ideally imaged directly within the intact tumor tissue in a label-free way. In this study, we investigated lipid accumulation and distribution in living zebrafish larvae developing a tumor by means of coherent anti-Stokes Raman scattering microscopy. Quantitative textural features based on radiomics revealed higher lipid accumulation in oncogene-expressing larvae compared to healthy ones. This high lipid accumulation could reflect an altered lipid metabolism in the hyperproliferating oncogene-expressing cells.

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