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Inhibitory effect of fatty acids on the binding of androgen receptor and R1881.

Unsaturated long chain fatty acids are known to inhibit the binding between estrogen and estrogen receptor, or progesterone and progesterone receptor in rat uterus. The effects of long chain fatty acids on the binding between androgen receptor of castrated rat prostate and 3H-R1881 were studied. The binding was not affected by saturated fatty acids such as palmitic acid (16:0) or stearic acid (18:0). But unsaturated fatty acids such as oleic acid (18:1), arachidonic acid (20:4) and docosahexaenoic acid (22:6) inhibited the binding between androgen receptor and 3H-R1881. The inhibitory effect of arachidonic acid was dose dependent. Scatchard analysis showed that the addition of arachidonic acid markedly decrease the number of binding sites of androgen receptor. But the dissociation constant was not affected. The inhibitory effect of arachidonic was not a competitive one.

Animals↗

Enzyme activity of the cytochrome P-450 monooxygenase system in the presence of single chain lipid molecules.

The influence of single chain lipids on the 7-ethoxycoumarin O-deethyase activity of the reconstituted binary protein complex of isolated cytochrome P450 and NADPH-cytochrome P450 reductase has been examined. The enzyme activity of this binary enzyme complex has been shown to be influenced by (i) altering the complexation process of both proteins, (ii) by altering the catalytic cycle time of the active binary protein complex and (iii) by altering the fraction of substrate molecules at the catalytic center of the enzyme. Competitive inhibition was measured for all single chain molecules. The following dissociation coefficients of substrate and lipids used for the catalytic center of the protein were obtained: 110 microM 7-ethoxycoumarin (substrate), 1.1 microM MOG (1-monooleoyl-rac-glycerol), 0.3 microM SPH (D-sphingosine), 1.5 microM OA (oleic acid), 3.0 microM LPC (L-alpha-lysophosphatidyl-choline), 15.5 microM MSG (1-monostearoyl-rac-glycerol), 9.5 microM AA (arachidonic acid), 9.0 microM PaCar (palmitoyl-L-carnitine), 3.5 microM MPG (2-monopalmitoyl-glycerol), 1.5 microM LPI (L-alpha-lysophosphatidyl-inositol), 50 microM LA (lauric acid), 60 microM MA (myristic acid), 85 microM PA (palmitic acid), >100 microM SA (stearic acid). Only competitive inhibition with the substrate molecule 7-ethoxycoumarin was observed for the single chain lipids LA, MA, PA, SPH, SA, and OA. Non-competitive effects were observed for MPG (-0.03 microM(-1)), PaCar (-0.02 microM(-1)), MSG (-0.023 microM(-1)), LPC (-0.03 microM(-1)), AA (-0.03 microM(-1)), and MOG (+0.04 microM(-1)). The negative sign indicates that the cycle time of the working binary complex is enlarged. The positive sign indicates that the formation of the binary complex is enhanced by MOG.

7-Alkoxycoumarin O-Dealkylase↗

Thiazolidinediones downregulate stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes.

Thiazolidinediones (TZDs) are known to have potent increases of insulin sensitivity. Because peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a receptor for TZDs, is mainly expressed in adipocytes, we tried to search the TZD-targeted genes in mouse 3T3-L1 adipocytes. By the mRNA differential display method, one band repressed by troglitazone was obtained, which corresponded to the partial sequences of the stearoyl-CoA desaturase 1 (SCD1) gene. Troglitazone dramatically decreased SCD1 mRNA levels in 3T3-L1 adipocytes in a dose-dependent manner. Pioglitazone also repressed the SCD1 mRNA expression, whereas WY-14,643 had no apparent effect. Both troglitazone and pioglitazone raised the composition (weight percentage) of myristic acid (C14:0), palmitic acid (C16:0), and stearic acid (C18:0), but lowered the composition of the delta9-cis desaturated fatty acids such as myristoleic acid (C14:1, delta9), palmitoleic acid (C16:1, delta9), oleic acid (C18:1, delta9), and linoleic acid (C18:2, delta9,12). These results indicate that TZDs repress SCD1 activity in 3T3-L1 adipocytes via downregulating SCD1 enzyme gene expression.

3T3 Cells↗

Studies on the metabolism of d-Limonene (p-Mentha-1,8-diene). III. Effects of d-Limonene on the lipids and drug-metabolizing enzymes in rat livers.

1. After a single oral dose of d-limonene (200-1200 mg/kg) no effects were observed on liver triglyceride, microsomal protein, cytochrome b5, and the drug-metabolizing enzymes. Glycogen content was slightly decreased at doses higher than 800 mg/kg, and cytochrome P-450 and delta-aminolaevulinic acid synthetase activity was slightly increased at 1200 mg/kg. 2. After repeated treatment (400 mg/kg/day) for 30 days, the relative liver weight and hepatic phospholipid content were only slightly increased, and liver and serum cholesterol were decreased 49 and 8%, respectively. Of the phospholipid fatty acids, palmitic, linoleic and arachidonic acids were increased, and stearic acid was decreased. Aminopyrine demethylase and aniline hydroxylase were increased 26 and 22%, respectively, and cytochrome P-450 and b5 were likewise increased 31 and 30%.

5-Aminolevulinate Synthetase↗

[Drug-protein binding in elderly subjects].

It is important to know the magnitude of serum-protein binding of drug dynamics in vivo. The authors investigated the effects of a variety of serum free fatty acids in elderly subjects. Serum albumin levels and ceftezole (CTZ)-protein binding in elderly subjects were lower than in younger subjects. No significant difference was noted between the two groups in regard to total free fatty acid (T-FFA) level. However, compared with younger subjects, palmitolic and oleic acid were higher and myristic and linoleic acid were lower in elderly subjects, suggesting that free fatty acid (FFA) undergoes qualitative changes due to ageing. In elderly subjects CTZ-binding correlated negatively with T-FFA, oleic acid and linoleic acid, but positively with stearic acid. Oleic acid decreased CTZ-protein binding. This decrease was higher than that due to decreased albumin levels in elderly subjects with albumin levels less than 4.0 g/dl. These findings indicated that reduced protein binding in elderly subjects is due to decreased serum albumin and changes in FFA constitution with ageing. Therefore it was suggested that drug-albumin binding may change due to the competitive action of albumin sites, and albumin-drug binding capacity. Since drug-protein binding capacity seriously affect metabolism, excretion, efficacy and side effects due to the presence of free drugs, these aspects require further investigation in elderly subjects.

Adult↗

Effects of exposure to Freon 11, 1,1,1-trichloroethane or perchloroethylene on the lipid and fatty-acid composition of rat cerebral cortex.

Organic solvents are often present as mixtures in various industrial and house-hold products. The adverse effects arising from exposure to these solvents have often been generalized to concern the whole group of solvents. In an examination of the possibility that organic solvents have general effects on experimental animals, rats were continuously exposed to vapors of the halogenated solvents Freon 11, perchloroethylene, and 1,1,1-trichloroethane. The lipid composition and fatty-acid pattern of ethanolamine phosphoglyceride from the cerebral cortex were analyzed. It was observed that only perchloroethylene had effects on the brain lipid composition. Cholesterol and total phospholipids were slightly reduced. Among the fatty acids the proportion of stearic acid was reduced and those of docosapentanoic, 22:5 (N = 6), and of docosahexanoic, 22:6 (N = 3), acids were increased. The changes in the fatty-acid pattern indicate that an alteration occurs in the desaturation of fatty acids. It seems probable that the chloroethylenes have specific effects on the fatty-acid pattern of brain phospholipids not shared by other solvents.

Animals↗

Characterization of cocoa butter extracted from hybrid cultivars of Theobroma cacao L.

Cocoa butter is the most important fat used in the confectionery and chocolate industries. The main objective of the present study was to determine the physical and chemical characteristics of cocoa butter extracted from hybrid cultivars belonging to the germplasm bank of the Fondo Nacional de Investigaciones Agropecuarias (National Foundation for Agricultural Research). AOAC methods were used for the assessment of the proximal composition of the beans, physical and chemical characteristics as well as for the fatty acid profile of the fat. It was found that there were statistical differences in the proximate composition of the cocoa beans among the cultivars studied as well as the iodine and saponification indices of the butter. Saturated fatty acids were present in higher proportions than unsaturated fatty acids, with palmitic and stearic acid as the main fractions. Oleic acid content was higher than linoleic acid. The fatty acid profile found is the main factor that influences the hard texture of the cocoa butter from Venezuelan cocoa hybrids cultivars.

Butter↗

[Effect of angiotensin II on the pattern of plasma free fatty acids in 2 hypertension models in rabbits].

The effect of exogenous angiotensin II on the spectrum of nonesterified fatty acids (NEFA) in blood plasma was studied by gas-chromatographic analysis in 10 normotonic rabbits, 12 rabbits with experimental hypertension induced by sinoaortic denervation, and in 14 rabbits with experimental renal hypertension. One minute after injection of angiotensin II, the following changes were found in the spectrum of NEFA: increase in the fraction of saturated, and decrease in the fraction of unsaturated NEFA;the intensity of these changes was higher in the animals with renal hypertension than in those with hypertension induced by sinoaortic denervation, and lowest in the normotonic rabbits. Thirty to sixty minutes after injection the above changes further gained in intensity in both models of hypertension, whereas in normotonic rabbits the changes rather receded. A growing dominance of palmitic acid, persistent elevation of stearic acid, decreases in the levels of monoenolic oleic and palmitoleic acids as well as of polyenolic fatty acids were observed.

Angiotensin II↗

[Some peculiarities of brain phospholipids in deep sea fishes].

Total phospholipids (PL) as well as the content of various phospholipid classes and their fatty acid composition have been investigated in the brain of mesopelagic and abyssal marine teleosts. These species were compared to shallow water ones. The brain of deep sea fishes was found to be very poor in PL as compared to the brain of mesopelagic ans surface water species. No differences concerning the brain PL content were revealed between the two last mentioned groups. The relative content of separate PL classes was very similar in all the species studied irrespectively of the depth of their habitat. Peculiarities were found in fatty acid composition of individual PL from deep sea species as compared to surface ones. The deeper the habitat, the lower the content of saturated fatty acids, especially of the stearic acid. The lowest content of saturated fatty acids, maximum level of polyenoic fatty acids as well as some peculiarities in the relative content of particular fatty acids were found in the brain of ultraabyssal (6, 000 m) Leucicorus sp.

Adaptation, Physiological↗

[Studies on chemical constituents of Forsythia suspensa (Thunb) Vahl].

OBJECTIVE: To study the chemical constituents of Forsythia suspensa. METHOD: Basedon silicacolumn chromatography, of which six compounds were obtained from the alcohol extract of F. suspensa, three identified by physicochemical and spectroscopic analyses. RESULT: The three compounds were identified as stearic acid, palmitic acid and beta-sitosterol. CONCLUSION: The three compounds were separated from F. suspensa fruits for the first time.

Forsythia↗

[Chemical composition of Fordia cauliflora Hemsl].

OBJECTIVE: To study chemical constituents of the root of Fordia cauliflora. METHOD: Three compounds were obtained from the ethanolic extract of the roots of F. cauliflora by silica column chromatography, and identified by physico-chemical and spectroscopic analysis. RESULT: The compounds were identified as stearic acid, palmitic acid and beta-sitosterol. CONCLUSION: These compounds were obtained from this plant for the first time.

Fabaceae↗

Change in cholesterol levels and in lipid fatty acid composition in safflower oil fed lambs.

The influence of safflower oil supplemented (5%) diet both on cholesterol level and on lipid fatty acid composition was investigated in serum, liver and muscle (Longissimus dorsi) of lambs. The fatty acid pattern varied similarly in all the three tissues. An increase in linoleic acid and in some other polyunsaturated fatty acids, and a simultaneous reduction of the saturated fatty acids (mostly palmitic and stearic acid) were observed. On the contrary, cholesterol content decreased notably (44%) in the liver, with a much less evident decrease in serum and muscle of treated animals.

Animals↗