scholarly journals Stearic acid blunts growth-factor signaling via oleoylation of GNAI proteins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hana Nůsková ◽  
Marina V. Serebryakova ◽  
Anna Ferrer-Caelles ◽  
Timo Sachsenheimer ◽  
Christian Lüchtenborg ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Protein Function ◽  
Functional Outcomes ◽  
Covalent Attachment ◽  
Growth Factor Signaling ◽  
Egfr Signaling ◽  
Akt Activation ◽  
Functional Consequences ◽  
Protein Acylation

AbstractCovalent attachment of C16:0 to proteins (palmitoylation) regulates protein function. Proteins are also S-acylated by other fatty acids including C18:0. Whether protein acylation with different fatty acids has different functional outcomes is not well studied. We show here that C18:0 (stearate) and C18:1 (oleate) compete with C16:0 to S-acylate Cys3 of GNAI proteins. C18:0 becomes desaturated so that C18:0 and C18:1 both cause S-oleoylation of GNAI. Exposure of cells to C16:0 or C18:0 shifts GNAI acylation towards palmitoylation or oleoylation, respectively. Oleoylation causes GNAI proteins to shift out of cell membrane detergent-resistant fractions where they potentiate EGFR signaling. Consequently, exposure of cells to C18:0 reduces recruitment of Gab1 to EGFR and reduces AKT activation. This provides a molecular mechanism for the anti-tumor effects of C18:0, uncovers a mechanistic link how metabolites affect cell signaling, and provides evidence that the identity of the fatty acid acylating a protein can have functional consequences.

scholarly journals DGAT1 is a lipid metabolism oncoprotein that enables cancer cells to accumulate fatty acid while avoiding lipotoxicity

2020 ◽  
Author(s):  
Daniel J. Wilcock ◽  
Andrew P. Badrock ◽  
Rhys Owen ◽  
Melissa Guerin ◽  
Andrew D. Southam ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cell Growth ◽  
Cancer Cells ◽  
Melanoma Cell ◽  
Drug Targets ◽  
Lipid Peroxides ◽  
Acid Oxidation ◽  
Growth Factor Signaling ◽  
Bona Fide

ABSTRACTDysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in non-transformed cells, but surprisingly not in cancer cells. Molecules underlying this cancer adaptation may provide new drug targets. Here, we identify Diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, as a frequently up-regulated oncoprotein allowing cancer cells to tolerate excess fatty acids. DGAT1 over-expression alone induced melanoma in zebrafish melanocytes, and co-operated with oncogenic BRAF or NRAS for more rapid melanoma formation. Mechanistically, DGAT1 stimulated melanoma cell growth through sustaining mTOR kinase–S6 kinase signaling and suppressed cell death by tempering fatty acid oxidation, thereby preventing accumulation of reactive oxygen species including lipid peroxides.SIGNIFICANCEWe show that DGAT1 is a bona fide oncoprotein capable of inducing melanoma formation and co-operating with other known drivers of melanoma. DGAT1 facilitates enhanced fatty acid acquisition by melanoma cells through suppressing lipototoxicity. DGAT1 is also critical for maintaining S6K activity required for melanoma cell growth.

scholarly journals Direct modulation of G-proteins by polyunsaturated fatty acids: a novel eicosanoid-independent regulatory mechanism in the developing lung

1997 ◽  
Vol 326 (3) ◽  
pp. 725-730 ◽  
Author(s):  
Somnath MUKHOPADHYAY ◽  
Sarah J. RAMMINGER ◽  
Mark McLAUGHLIN ◽  
Lorraine GAMBLING ◽  
Richard E. OLVER ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
G Protein ◽  
Protein Function ◽  
Time Course ◽  
Apical Membrane ◽  
Saturated Fatty Acids ◽  
Hydrolysis Rate ◽  
Gtpase Activity

Basal and fatty-acid-modulated G-protein function was studied in 1–3-day-pre-term, fetal guinea-pig, type II (fATII) pneumocyte apical membrane. Unstimulated (tonic) high-affinity GTPase activity (measured as [γ-32P]GTP hydrolysis rate) was high and 77% pertussis toxin-insensitive. Alteration of this activity was used as a marker of G-protein regulation. Arachidonic acid (AA) showed a dose-dependent (IC50 = 48±8 μM) inhibition of activity at concentrations significantly below critical micellar concentrations; this effect was mimicked by other polyunsaturated fatty acids (IC50 for linoleic acid = 47±2 μM; IC50 for oleic acid= 106±11 μM). Saturated fatty acids showed no effect. The effect of AA on ouabain-insensitive ATPases in the same preparation was significantly lower, suggesting a specificity of the GTPase modulation effect. AA modulation of GTPase activity was not attenuated by blocking eicosanoid metabolism with inhibitors of 5′-lipoxygenase, cyclo-oxygenase and P-450. In order to explore further the mechanism of AA–G-protein interaction, the effect of AA on the time course and equilibrium binding of [35S]GTP[S] to apical membrane was studied. Consistent with our GTPase assay data, AA inhibited binding with an IC50 value of 71±1 μM; stearic acid did not mimic this effect. This is the first report of unsaturated-fatty-acid-specific modulation of lung G-protein function: since AA also up-regulates perinatal lung alveolar Na+ transport, we suggest this lipid/G-protein switch helps maintain pulmonary fluid homoeostasis around birth.

Platelet Aggregation in Finnish Men and Its Relation to Fatty Acids in Platelets, Plasma and Adipose Tissue

1985 ◽  
Vol 54 (03) ◽  
pp. 563-569 ◽  
Author(s):  
M K Salo ◽  
E Vartiainen ◽  
P Puska ◽  
T Nikkari
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Acid Composition ◽  
Saturated Fatty Acids ◽  
Free Living ◽  
Ω3 Fatty Acids ◽  
Induced Aggregation

SummaryPlatelet aggregation and its relation to fatty acid composition of platelets, plasma and adipose tissue was determined in 196 randomly selected, free-living, 40-49-year-old men in two regions of Finland (east and southwest) with a nearly twofold difference in the IHD rate.There were no significant east-southwest differences in platelet aggregation induced with ADP, thrombin or epinephrine. ADP-induced platelet secondary aggregation showed significant negative associations with all C20-C22 ω3-fatty acids in platelets (r = -0.26 - -0.40) and with the platelet 20: 5ω3/20: 4ω 6 and ω3/ ω6 ratios, but significant positive correlations with the contents of 18:2 in adipose tissue (r = 0.20) and plasma triglycerides (TG) (r = 0.29). Epinephrine-induced aggregation correlated negatively with 20: 5ω 3 in plasma cholesteryl esters (CE) (r = -0.23) and TG (r = -0.29), and positively with the total percentage of saturated fatty acids in platelets (r = 0.33), but had no significant correlations with any of the ω6-fatty acids. Thrombin-induced aggregation correlated negatively with the ω3/6ω ratio in adipose tissue (r = -0.25) and the 20: 3ω6/20: 4ω 6 ratio in plasma CE (r = -0.27) and free fatty acids (FFA) (r = -0.23), and positively with adipose tissue 18:2 (r = 0.23) and 20:4ω6 (r = 0.22) in plasma phospholipids (PL).The percentages of prostanoid precursors in platelet lipids, i. e. 20: 3ω 6, 20: 4ω 6 and 20 :5ω 3, correlated best with the same fatty acids in plasma CE (r = 0.32 - 0.77) and PL (r = 0.28 - 0.74). Platelet 20: 5ω 3 had highly significant negative correlations with the percentage of 18:2 in adipose tissue and all plasma lipid fractions (r = -0.35 - -0.44).These results suggest that, among a free-living population, relatively small changes in the fatty acid composition of plasma and platelets may be reflected in significant differences in platelet aggregation, and that an increase in linoleate-rich vegetable fat in the diet may not affect platelet function favourably unless it is accompanied by an adequate supply of ω3 fatty acids.

EFFECT OF GINGER, LEMURU FISH OIL SAPONIFICATION AND OLIVE OIL ON COMPOSITION FATTY ACID OF BEEF

2014 ◽  
Vol 4 (1) ◽  
pp. 31-39
Author(s):  
Siwitri Kadarsih
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fish Oil ◽  
Olive Oil ◽  
Rice Bran ◽  
Dry Matter ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Omega 3 ◽  
Omega 6

The objective was to get beef that contain unsaturated fatty acids (especially omega 3 and 6), so as to improve intelligence, physical health for those who consume. The study design using CRD with 3 treatments, each treatment used 4 Bali cattle aged approximately 1.5 years. Observations were made 8 weeks. Pasta mixed with ginger provided konsentrat. P1 (control); P2 (6% saponification lemuru fish oil, olive oil 1%; rice bran: 37.30%; corn: 62.70%; KLK: 7%, ginger paste: 100 g); P3 (lemuru fish oil saponification 8%, 2% olive oil; rice bran; 37.30; corn: 62.70%; KLK: 7%, ginger paste: 200 g). Konsentrat given in the morning as much as 1% of the weight of the cattle based on dry matter, while the grass given a minimum of 10% of the weight of livestock observation variables include: fatty acid composition of meat. Data the analyzies qualitative. The results of the study showed that the composition of saturated fatty acids in meat decreased and an increase in unsaturated fatty acids, namely linoleic acid (omega 6) and linolenic acid (omega 3), and deikosapenta deikosaheksa acid.Keywords : 

Fatty Acid Profile and In Vitro Anticancer Activity of Two Marine Sponge- Associated Bacteria

2020 ◽  
Vol 16 (9) ◽  
pp. 1273-1280
Author(s):  
Giuseppina Tommonaro ◽  
Ali M. El-Hagrassi ◽  
Walid Fayad ◽  
Carmine Iodice ◽  
Kamel H. Shaker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Colorectal Carcinoma ◽  
Cell Line ◽  
Marine Sponge ◽  
Hct116 Cell ◽  
Associated Bacteria ◽  
Sponge Associated Bacteria ◽  
Human Colorectal Carcinoma

Background: Colorectal cancer represents one of the prominent causes of mortality worldwide in men and women. The objective of this study was to search for new potential anticancer compounds, both in prevention and treatment of colorectal cancer. The anticancer potential of marine bacterial extracts against Human colorectal carcinoma cell line (HCT116) was evaluated as well as the partial identification of bioactive metabolites. Methods: All bacterial extracts were tested for their cytotoxicity against HCT116 cell line by means of MTT assay. The highly cytotoxic dichloromethane extracts of marine sponge-associated bacteria Vibrio sp. and Bacillus sp. were analyzed by GC-MS. Results: Two fractions, Vib3 and Bac3, exhibited a very interesting cytotoxicity against human colorectal carcinoma (HCT116) cell line, with a percentage of cytotoxicity of 96.04 % and 29.48 %, respectively. Discussion: The GC-MS analysis revealed the presence of two major fatty acids, palmitic and oleic acids, in Vib3 fraction and fatty acid esters and phenolic compounds in Bac3 fraction. Conclusion: Based on previous literature, it may be hypothesized that the anticancer activity of bacterial extracts could be, at least partially, to the fatty acids fraction.

Content and composition of phospholipids, fatty acids and sterols in commercial natural phospholipid excipients

2020 ◽  
Vol 16 ◽  
Author(s):  
Luxia Zheng ◽  
Xiong Shen ◽  
Yingchun Wang ◽  
Jian Liang ◽  
Mingming Xu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cluster Analysis ◽  
Fatty Acid ◽  
High Performance ◽  
Comprehensive Evaluation ◽  
Phospholipid Fatty Acid ◽  
Egg Yolk ◽  
Systematic Research ◽  
Manufacturing Enterprises ◽  
The Many

Background: Phospholipids are widely used in food and pharmaceutical industry as functional excipients. In spite of the many analytical methods reported, there are very limited reports concerning systematic research and comparison of phospholipid excipients. Objective: To present a comprehensive evaluation of commercial natural phospholipid excipients (CNPEs). Methods: Seventeen batches of CNPEs from five manufacturing enterprises, isolated either from soybean or egg yolk, were investigated. The content and composition of phospholipids, fatty acids and sterols as a whole were considered as the evaluative index of CNPEs. Eight kinds of phospholipids were determined by supercritical fluid chromatography (SFC), twenty-one kinds of fatty acids were determined by gas chromatography (GC) after boron trifluoride-methanol derivatization, and nine kinds of sterols were determined by high performance liquid chromatography (HPLC) after separation and derivatization of the unsaponifiable matter. Cluster analysis was employed for classification and identification of the CNPEs. Results: The results showed that each kind of CNPEs had its characteristic content and composition of phospholipids, fatty acids and sterols. Seventeen batches of samples were divided into eight groups in cluster analysis. CNPEs of the same type from different source (soybean or egg yolk) or enterprises presented different content and composition of phospholipids, fatty acids and sterols. Conclusion: Each type of CNPEs had its characteristic content and composition of phospholipid, fatty acid and sterol. The compositions of phospholipid, fatty acid and sterol as a whole can be applied as an indicator of the quality and characteristics for CNPEs.

In Vitro Anticancer Activity of Virgin Coconut Oil and its Fractions in Liver and Oral Cancer Cells

2020 ◽  
Vol 19 (18) ◽  
pp. 2223-2230 ◽  
Author(s):  
Poonam Verma ◽  
Sanjukta Naik ◽  
Pranati Nanda ◽  
Silvi Banerjee ◽  
Satyanarayan Naik ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Oral Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Coconut Oil ◽  
Virgin Coconut Oil ◽  
Anticancer Efficacy ◽  
Oral Cancer Cells

Background: Coconut oil is an edible oil obtained from fresh, mature coconut kernels. Few studies have reported the anticancer role of coconut oil. The fatty acid component of coconut oil directly targets the liver by portal circulation and as chylomicron via lymph. However, the anti-cancer activity of coconut oil against liver cancer cells and oral cancer cells is yet to be tested. The active component of coconut oil, that is responsible for the anticancer activity is not well understood. In this study, three different coconut oils, Virgin Coconut Oil (VCO), Processed Coconut Oil (PCO) and Fractionated Coconut Oil (FCO), were used. Objective: Based on previous studies, it can be hypothesized that fatty acids in coconut oil may have anticancer potential and may trigger cell death in cancer cell lines. Methods: Each cell line was treated with different concentrations of Virgin Coconut Oil (VCO), Processed Coconut Oil (PCO) and Fractionated Coconut Oil (FCO). The treated cells were assayed by MTT after 72 hr of incubation. The fatty acid composition of different coconut oils was analyzed by gas chromatography. Result: Different concentrations of coconut oils were used to treat the cells. Interestingly, the anticancer efficacy of VCO, PCO and FCO was not uniform, rather the efficacy varied from cell line to cell line. Only 20% VCO showed significant anticancer activity in HepG2 cells in comparison to 80% PCO against the KB cell line. Remarkably, 20% of PCO and 5% of FCO showed potential growth inhibition in the KB cell line as compared to 80% PCO in HepG2 cells. Moreover, there was a difference in the efficacy of VCO, PCO and FCO, which might be due to their fatty acid composition. Comparing the anticancer efficacy of VCO, PCO and FCO in this study helped to predict which class of fatty acids and which fatty acid might be associated with the anticancer activity of VCO. Conclusion: This study shows that VCO, PCO and FCO have anticancer efficacy and may be used for the treatment of cancer, especially liver and oral cancer.

Chlorella vulgaris as a Source of Essential Fatty Acids and Micronutrients: A Brief Commentary

2017 ◽  
Vol 10 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Hércules Rezende Freitas
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Culture Medium ◽  
Essential Fatty Acids ◽  
Total Lipid Content ◽  
Dietary Quality ◽  
Negative Effects ◽  
Algae Biomass ◽  
Dietary Consumption ◽  
Acid Consumption

Polyunsaturated fatty acids (PUFAs) comprise about 35-40% of the total lipid content from green algaeChlorella, reaching up to 24% linoleic acid and 27% α-linolenic acid inC. vulgaris. Also, microalgae nutrient composition may be modulated by changes in the culture medium, increasing fatty acid and microelement concentrations in the algae biomass. PUFAs, such as α-linolenic (n-3) and linoleic (n-6) acids, as well as its derivatives, are considered essential for dietary consumption, and their ability to regulate body chemistry has been recently explored in depth. A balanced fatty acid consumption is shown to counteract the negative effects of western diets, such as chronic inflammation and glucose intolerance. In this brief commentary, technological and practical uses ofC. vulgarisare explored as means to improve dietary quality and, ultimately, human health.

In vivo study of the biosynthesis of long-chain fatty acids using deuterated water

1995 ◽  
Vol 269 (2) ◽  
pp. E247-E252 ◽  
Author(s):  
H. O. Ajie ◽  
M. J. Connor ◽  
W. N. Lee ◽  
S. Bassilian ◽  
E. A. Bergner ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Chain Elongation ◽  
Deuterated Water ◽  
De Novo Synthesis ◽  
Isotopomer Distribution ◽  
Long Chain ◽  
Mass Isotopomer

To determine the contributions of preexisting fatty acid, de novo synthesis, and chain elongation in long-chain fatty acid (LCFA) synthesis, the synthesis of LCFAs, palmitate (16:0), stearate (18:0), arachidate (20:0), behenate (22:0), and lignocerate (24:0), in the epidermis, liver, and spinal cord was determined using deuterated water and mass isotopomer distribution analysis in hairless mice and Sprague-Dawley rats. Animals were given 4% deuterated water for 5 days or 8 wk in their drinking water. Blood was withdrawn at the end of these times for the determination of deuterium enrichment, and the animals were killed to isolate the various tissues for lipid extraction for the determination of the mass isotopomer distributions. The mass isotopomer distributions in LCFA were incompatible with synthesis from a single pool of primer. The synthesis of palmitate, stearate, arachidate, behenate, and lignocerate followed the expected biochemical pathways for the synthesis of LCFAs. On average, three deuterium atoms were incorporated for every addition of an acetyl unit. The isotopomer distribution resulting from chain elongation and de novo synthesis can be described by the linear combination of two binomial distributions. The proportions of preexisting, chain elongation, and de novo-synthesized fatty acids as a percentage of the total fatty acids were determined using multiple linear regression analysis. Fractional synthesis was found to vary, depending on the tissue type and the fatty acid, from 47 to 87%. A substantial fraction (24-40%) of the newly synthesized molecules was derived from chain elongation of unlabeled (recycled) palmitate.

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