scholarly journals Unsaturated fatty acids as endogenous inhibitors of tamoxifen binding to anti-oestrogen-binding sites

1986 ◽  
Vol 237 (3) ◽  
pp. 749-755 ◽  
Author(s):  
P L H Hwang
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Binding Sites ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Biological Significance ◽  
Dependent Manner ◽  
Rat Serum ◽  
Endogenous Ligands ◽  
Serum Extract

It is known that triphenylethylene anti-oestrogens such as tamoxifen bind to specific high-affinity anti-oestrogen-binding sites, which are distinct from oestrogen receptors. These binding sites are widely distributed in human and animal tissues, but their function and endogenous ligands are unknown. By using [3H]tamoxifen and a rat liver microsomal fraction, a radio-ligand-binding assay was developed in an attempt to identify endogenous ligands for the anti-oestrogen-binding sites in the rat. An ether extract of rat serum inhibited [3H]tamoxifen binding to rat liver binding sites in a dose-dependent manner. Identification of the active serum constituents that inhibited [3H]tamoxifen binding was achieved by g.l.c.-mass spectrometry after preliminary purification of a rat serum extract by silica-gel t.l.c. Three unsaturated fatty acids (oleic, linoleic and arachidonic) accounted for about 50% of the total inhibiting activity of the serum extract. The concentrations of these fatty acids required to inhibit [3H]tamoxifen binding were in the range of 10-100 microM, comparable with those found in the rat circulation under physiological conditions. Saturated fatty acids present in rat serum (palmitic and stearic) did not inhibit [3H]tamoxifen binding. A survey of other fatty acids revealed that, in general, unsaturated fatty acids were far more potent than saturated fatty acids in inhibiting [3H]tamoxifen binding. These studies demonstrate that unsaturated fatty acids are quantitatively the most important circulating inhibitors of [3H]tamoxifen binding to the anti-oestrogen-binding sites. The biological significance of their interaction with these sites, however, remains to be clarified.

scholarly journals Interaction of unsaturated fatty acids with anti-oestrogen-binding sites

1987 ◽  
Vol 243 (2) ◽  
pp. 359-364 ◽  
Author(s):  
P L H Hwang
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Binding Site ◽  
Binding Affinity ◽  
Binding Sites ◽  
Unsaturated Fatty Acids ◽  
Biological Significance ◽  
Competitive Inhibitor ◽  
Apparent Dissociation Constant ◽  
Endogenous Ligands

Specific high-affinity binding sites for non-steroidal anti-oestrogens such as tamoxifen have been identified in many animal and human tissues. The function of these binding sites and the nature of their endogenous ligands are currently unknown. Our laboratory has previously reported that unsaturated fatty acids at micromolar concentrations inhibited [3H]tamoxifen binding to the anti-oestrogen-binding sites in rat liver, raising the possibility that fatty acids might represent endogenous ligands for these sites. These studies have now been extended to examine the mechanism by which fatty acids inhibit [3H]tamoxifen binding to the anti-oestrogen-binding site. Saturation analysis revealed that increasing concentrations of oleic acid progressively decreased the apparent binding affinity of these sites for [3H]tamoxifen without decreasing the total number of binding sites; however, the apparent dissociation constant did not vary linearly with the prevailing oleic acid concentration, suggesting that the inhibition of [3H]tamoxifen binding by fatty acid was not competitive in nature. Kinetic studies of [3H]tamoxifen binding showed that oleic acid did not affect the rate of association, but increased the rate of dissociation of [3H]tamoxifen from the anti-oestrogen-binding site; the latter finding would not be expected if oleic acid acted as a competitive inhibitor. Furthermore, incubation of a rat microsomal fraction with [3H]oleic acid in the absence and presence of excess non-radioactively labelled tamoxifen also failed to demonstrate direct competition between oleic acid and tamoxifen for the same binding site. It is concluded that oleic acid, and presumably other unsaturated fatty acids, do not compete for the anti-oestrogen-binding site and probably reduce its tamoxifen-binding affinity by some other mechanism, such as perturbation of the lipid environment of the binding site. The biological significance of this interaction of unsaturated fatty acids with the anti-oestrogen-binding site remains to be elucidated.

scholarly journals Fatty acid metabolism in the perfused rat liver

1970 ◽  
Vol 119 (3) ◽  
pp. 525-533 ◽  
Author(s):  
H. A. Krebs ◽  
R. Hems
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Body ◽  
Unsaturated Fatty Acids ◽  
Ketone Bodies ◽  
Saturated Fatty Acids ◽  
Perfused Rat Liver ◽  
Body Formation ◽  
Body Production ◽  
Chain Fatty Acids

1. The formation of acetoacetate, β-hydroxybutyrate and glucose was measured in the isolated perfused rat liver after addition of fatty acids. 2. The rates of ketone-body formation from ten fatty acids were approximately equal and independent of chain length (90–132μmol/h per g), with the exception of pentanoate, which reacted at one-third of this rate. The [β-hydroxybutyrate]/[acetoacetate] ratio in the perfusion medium was increased by long-chain fatty acids. 3. Glucose was formed from all odd-numbered fatty acids tested. 4. The rate of ketone-body formation in the livers of rats kept on a high-fat diet was up to 50% higher than in the livers of rats starved for 48h. In the livers of fat-fed rats almost all the O2 consumed was accounted for by the formation of ketone bodies. 5. The ketone-body concentration in the blood of fat-fed rats rose to 4–5mm and the [β-hydroxybutyrate]/[acetoacetate] ratio rose to 11.5. 6. When the activity of the microsomal mixed-function oxidase system, which can bring about ω-oxidation of fatty acids, was induced by treatment of the rat with phenobarbitone, there was no change in the ketone-body production from fatty acids, nor was there a production of glucose from even-numbered fatty acids. The latter would be expected if ω-oxidation occurred. Thus ω-oxidation did not play a significant role in the metabolism of fatty acids. 7. Arachidonate was almost quantitatively converted into ketone bodies and yielded no glucose, demonstrating that gluconeogenesis from poly-unsaturated fatty acids with an even number of carbon atoms does not occur. 8. The rates of ketogenesis from unsaturated fatty acids (sorbate, undecylenate, crotonate, vinylacetate) were similar to those from the corresponding saturated fatty acids. 9. Addition of oleate together with shorter-chain fatty acids gave only a slightly higher rate of ketone-body formation than oleate alone. 10. Glucose, lactate, fructose, glycerol and other known antiketogenic substances strongly inhibited endogenous ketogenesis but had no effects on the rate of ketone-body formation in the presence of 2mm-oleate. Thus the concentrations of free fatty acids and of other oxidizable substances in the liver are key factors determining the rate of ketogenesis.

Uncoupling of cardiac cells by fatty acids: structure-activity relationships

1991 ◽  
Vol 260 (3) ◽  
pp. C439-C448 ◽  
Author(s):  
J. M. Burt ◽  
K. D. Massey ◽  
B. N. Minnich
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Decanoic Acid ◽  
Cardiac Cells ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Dependent Manner ◽  
Rat Heart Cells

The permeability and conductance of gap junctions between pairs of neonatal rat heart cells were rapidly and reversibly decreased by oleic acid in a dose- and time-dependent manner. Other unsaturated fatty acids (C-18: cis 6, 9, or 11, and C-18, 16, and 14, cis 9), saturated fatty acids (C-10, 12, and 14), and saturated fatty alcohols (C-8, 10, and 12) also caused uncoupling. The most effective compounds of the unsaturated and saturated fatty acid and saturated fatty alcohol series caused essentially complete uncoupling at comparable aqueous concentrations. However, oleic acid uncoupled cells at membrane concentrations as low as 1 mol%, whereas decanoic acid required upwards of 35 mol%. The channels that support the action potential remained functional at these same membrane concentrations. The data are discussed in terms of the possible mechanism by which these compounds cause uncoupling and the possible role of uncoupling by nonesterified free fatty acids in the initiation of arrhythmias during and after ischemic insults.

scholarly journals Effects of sublethal doses of gossypol on haematological properties and biochemical metabolites of male rabbit

2019 ◽  
Vol 27 (4) ◽  
pp. 237
Author(s):  
T.A. Ramadan ◽  
A.M. Rashad
Keyword(s):  
Fatty Acids ◽  
Blood Plasma ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Recovery Period ◽  
High Dose ◽  
Dependent Manner ◽  
Male Rabbit ◽  
Sublethal Doses ◽  
Dose Dependent

The purpose of this study was to investigate the effects of two sublethal doses of gossypol (GOS) (4 and 20 mg/kg of body weight), administered every other day, on some haematological, biochemical, enzymatic and electrolytic properties and amino and fatty acids in male rabbit blood plasma. The experiment lasted for 16 wk and included two phases: 1) administration period; rabbits were given the experimental doses of GOS for 8 wk; and 2) recovery period; rabbits were allowed 8 wk for complete withdrawal of drugs from the plasma. Results showed that low levels of gossypol increased (<em>P</em>&lt;0.01) haemoglobin, mean corpuscular haemoglobin and white blood cells compared to control. Plasma total protein was increased (<em>P</em>&lt;0.01) by the low GOS dose in both experimental phases. Likewise, glucose concentration was increased (<em>P</em>&lt;0.01) by the high GOS dose during the recovery period. Aspartate aminotransferase and alanine aminotransferase enzymes were increased (<em>P</em>&lt;0.01) by the high dose of GOS treatment only. Low GOS dose increased (<em>P</em>&lt;0.01) blood plasma Na+ concentration in the recovery period only. Results revealed that total essential amino acids (EAA), and EAA/non-EAA ratio were not affected in a dose-dependent manner during the treatment phase expect for plasma proline, which was increased along with non-EAA (<em>P</em>&lt;0.01) by high GOS dose. Additionally, GOS administration did not affect total unsaturated fatty acids (USFA), total saturated fatty acids (SFA) and SFA/USFA ratio in a dose-dependent manner. In conclusion, Gossypol treatment affected rabbit haematological parameters and biochemical properties of blood plasma in a dose-dependent manner.

scholarly journals Oleate Prevents Palmitate-Induced Atrophy via Modulation of Mitochondrial ROS Production in Skeletal Myotubes

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Hojun Lee ◽  
Jae-Young Lim ◽  
Seung-Jun Choi
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Mitochondrial Fission ◽  
Dependent Manner ◽  
Related Factors ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Ros ◽  
Skeletal Myotubes ◽  
Dose Dependent

Accumulation of saturated fatty acids contributes to lipotoxicity-related insulin resistance and atrophy in skeletal muscle. Conversely, unsaturated fatty acids like docosahexaenoic acid were proven to preserve muscle mass. However, it is not known if the most common unsaturated oleate will protect skeletal myotubes against palmitate-mediated atrophy, and its specific mechanism remains to be elucidated. Therefore, we investigated the effects of oleate on atrophy-related factors in palmitate-conditioned myotubes. Exposure of myotubes to palmitate, but not to oleate, led to an induction of fragmented nuclei, myotube loss, atrophy, and mitochondrial superoxide in a dose-dependent manner. Treatment of oleate to myotubes attenuated production of palmitate-induced mitochondrial superoxide in a dose-dependent manner. The treatment of oleate or MitoTEMPO to palmitate-conditioned myotubes led to inhibition of palmitate-induced mRNA expression of proinflammatory (TNF-αand IL6), mitochondrial fission (Drp1 and Fis1), and atrophy markers (myostatin and atrogin1). In accordance with the gene expression data, our immunocytochemistry experiment demonstrated that oleate and MitoTEMPO prevented or attenuated palmitate-mediated myotube shrinkage. These results provide a mechanism indicating that oleate prevents palmitate-mediated atrophy via at least partial modulation of mitochondrial superoxide production.

scholarly journals Reduction pathway of cis-5 unsaturated fatty acids in intact rat-liver and rat-heart mitochondria: assessment with stable-isotype-labelled substrates

1996 ◽  
Vol 313 (2) ◽  
pp. 581-588 ◽  
Author(s):  
Kou-Yi TSERNG ◽  
Shiow-Jen JIN ◽  
Lin-Su CHEN
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Rat Heart ◽  
Unsaturated Fatty Acids ◽  
Direct Reduction ◽  
Saturated Fatty Acids ◽  
Liver Mitochondria ◽  
Hydroxy Fatty Acids ◽  
Heart Mitochondria ◽  
Rat Heart Mitochondria

Besides the conventional isomerase-mediated pathway, unsaturated fatty acids with odd-numbered double bonds are also metabolized by reduction pathways with NADPH as cofactor. The relative contributions of these pathways were measured in intact rat-liver and rat-heart mitochondria with a novel stable isotope tracer technique. A mixture of equal amounts of unlabelled cis-5-enoyl-CoA and 13C4-labelled acyl-CoA of equal chain lengths was incubated with mitochondria. The isotope distribution of 3-hydroxy fatty acids produced from the first cycle of β-oxidation was analysed with selected ion monitoring by gas chromatograph-mass spectrometer. 3-Hydroxy fatty acids produced from the reduction pathway of unsaturated fatty acids were unlabelled (m+0) whereas those produced from saturated fatty acids were labelled (m+4). The m+0 content serves to indicate the extent of reduction pathway. Rotenone treatment was used to switch the pathway completely to reduction. The extent of m+0 enrichment in untreated mitochondria normalized to the m+0 enrichment of rotenone-treated mitochondria was the percentage of reduction pathway. With this technique, cis-4-decenoate was found to be metabolized completely by the reduction pathway in both liver and heart mitochondria. cis-5-Dodecenoate was metabolized essentially by the reduction pathway in liver mitochondria, but only to 75% in heart mitochondria. When the chain length was extended to cis-5-tetradecenoate, the reduction pathway in liver mitochondria decreased to 86% and that in heart mitochondria to 65%. The effects of carnitine, clofibrate and other conditions on the reduction pathway were also studied. Enrichments of the label on saturated fatty acids and 3-hydroxy fatty acids indicated that the major pathway of reduction was not by the direct reduction of the cis-5 double bond. Instead, it is most probably by a pathway that does not involve forming a reduced saturated fatty acid first.

scholarly journals Effect of freeze-dried pasture herbage on ileal digestibility of amino acids and fatty acids in chickens

2018 ◽  
Vol 63 (No. 6) ◽  
pp. 222-229
Author(s):  
M. Skřivan ◽  
M. Marounek ◽  
M. Englmaierová ◽  
E. Skřivanová ◽  
K. Růnová
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Trifolium Pratense ◽  
Unsaturated Fatty Acids ◽  
Control Diet ◽  
Saturated Fatty Acids ◽  
Dependent Manner ◽  
Ileal Digestibility ◽  
Freeze Dried ◽  
Negative Effect

The ileal digestibility of amino acids and fatty acids in young chickens fed control diet or experimental diets supplemented with freeze-dried pasture herbage at 20 or 40 g/kg was studied. Control diet contained wheat, maize, and soybean meal. Predominant species in the pasture herbage harvested in May were Lolium perenne, Festuca pratensis, and Trifolium pratense. Freeze-dried pasture herbage contained less protein (169 g/kg) and fat (24 g/kg) and more neutral detergent and acid detergent fibre (340 and 210 g/kg) and tannins (12.38 g/kg) than control diet. Concentrations of amino acids, except phenylalanine and threonine, were lower in pasture herbage than in control feed. In both the control feed and freeze-dried pasture herbage, unsaturated fatty acids occurred in higher proportions than saturated fatty acids. In freeze-dried pasture herbage linolenic acid was the main fatty acid. In chickens fed freeze-dried pasture herbage the ileal digestibility of amino acids and fatty acids decreased in a dose-dependent manner. Freeze-dried pasture herbage at 4% in diet had negative effect (P &lt; 0.05) on the digestibility of amino acids and fatty acids in comparison with control diet. But there was no significant effect of 2% freeze-dried pasture herbage in diet on amino acids digestibility. This suggests that pasture herbage contains anti-nutritional factors that inhibit proteolysis and lipolysis. The effect of pasture herbage on digestibility was variable. In chickens fed diets containing 4% freeze-dried pasture herbage, apparent ileal digestibility of amino acids varied from 0.39 (cysteine) to 0.91 (methionine). Variability in the ileal digestibility of fatty acids was less pronounced (from 0.65 to 0.89).

DEVELOPMENT OF AN EXPERIMENTAL MODEL OF AVITAMINOSIS F

2020 ◽  
Vol 20 (2) ◽  
pp. 38-40
Author(s):  
A. Levitsky ◽  
A. Lapinska ◽  
I. Selivanskaya
Keyword(s):  
Fatty Acids ◽  
Experimental Model ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Coconut Oil ◽  
The Body ◽  
Regulatory Function ◽  
Omega 3 ◽  
White Rats ◽  
Arachidonic Acids

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.

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 : 

Differential Effects of Dietary Fatty Acids on Body Composition and Adiposity

2020 ◽  
Vol 16 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Hadi Emamat ◽  
Zahra Yari ◽  
Hossein Farhadnejad ◽  
Parvin Mirmiran
Keyword(s):  
Fatty Acids ◽  
Body Composition ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Total Body Weight ◽  
Fat Distribution ◽  
Monounsaturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Dietary Fats ◽  
Total Body

Recent evidence has highlighted that fat accumulation, particularly abdominal fat distribution, is strongly associated with metabolic disturbance. It is also well-recognized that the metabolic responses to variations in macronutrients intake can affect body composition. Previous studies suggest that the quality of dietary fats can be considered as the main determinant of body-fat deposition, fat distribution, and body composition without altering the total body weight; however, the effects of dietary fats on body composition have controversial results. There is substantial evidence to suggest that saturated fatty acids are more obesogen than unsaturated fatty acids, and with the exception of some isomers like conjugate linoleic acid, most dietary trans fatty acids are adiposity enhancers, but there is no consensus on it yet. On the other hand, there is little evidence to indicate that higher intake of the n-3 and the n-6 polyunsaturated fatty acids can be beneficial in attenuating adiposity, and the effect of monounsaturated fatty acids on body composition is contradictory. Accordingly, the content of this review summarizes the current body of knowledge on the potential effects of the different types of dietary fatty acids on body composition and adiposity. It also refers to the putative mechanisms underlying this association and reflects on the controversy of this topic.

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