Non-esterified fatty acids impair endothelium-dependent vasodilation in rat mesenteric resistance vessels

2004 ◽  
Vol 107 (6) ◽  
pp. 625-629 ◽  
Author(s):  
Christopher A. R. SAINSBURY ◽  
Naveed SATTAR ◽  
John M. C. CONNELL ◽  
Chris HILLIER ◽  
John R. PETRIE
Keyword(s):  
Fatty Acids ◽  
Ascorbic Acid ◽  
Endothelial Dysfunction ◽  
Palmitic Acid ◽  
Resistance Arteries ◽  
Response Curves ◽  
Esterified Fatty Acids ◽  
Increased Risk ◽  
Significant Impairment

Elevated circulating levels of NEFAs (non-esterified fatty acids) are associated with states of insulin resistance and increased risk of vascular disease. Previous animal and human studies have demonstrated NEFA-induced endothelial dysfunction of large conduit arteries, reversible by the antioxidant ascorbic acid. We therefore investigated the effect of NEFAs on carbachol-induced endothelium-dependent vasodilation of rat resistance arteries in vitro using the technique of wire myography. In addition, we investigated the effect of co-incubation of NEFAs and ascorbic acid. Cumulative concentration–response curves to carbachol (endothelium-dependent vasodilation) and SNAP (S-nitroso-N-acetyl-DL-penicillamine; endothelium-independent vasodilation) were constructed. Those to carbachol were repeated following a 30 min incubation with either oleic acid (10−4 M) or palmitic acid (10−4 M), demonstrating significant impairment of endothelium-dependent vasodilation with both [P<0.05, comparison of pD2 values (the negative log concentration of agonist required to effect a 50% response)]. A cumulative concentration–response curve to carbachol was repeated following co-incubation with palmitic acid (10−4 M) and the antioxidant ascorbic acid (10−5 M), demonstrating an abolition of the previously observed endothelial dysfunction induced by palmitic acid. There was no impairment of vasodilation to SNAP following NEFA incubation. We conclude that NEFAs directly impair endothelial function in rat resistance arteries via an increase in oxidative stress at the vascular endothelium.

scholarly journals Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-α on the endothelium of murine aorta

2010 ◽  
Vol 299 (4) ◽  
pp. H1160-H1167 ◽  
Author(s):  
Saiprasad M. Zemse ◽  
Chin Wei Chiao ◽  
Rob H. P. Hilgers ◽  
R. Clinton Webb
Keyword(s):  
Endothelial Dysfunction ◽  
Interleukin 10 ◽  
Enos Expression ◽  
Response Curves ◽  
Female Mice ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
Significant Impairment

TNF-α is a proinflammatory cytokine and is an important mediator of maternal endothelial dysfunction leading to preeclampsia. In this study, we tested whether IL-10 protects against TNF-α-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice were incubated in Dulbecco's modified Eagle's medium in the presence of either vehicle (distilled H2O), TNF-α (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-α and IL-10 for 22 h at 37°C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-α (220 ng·kg−1·day−1) for 14 days. Aortic rings were isolated from in vitro and in vivo experiments and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5 mN. Endothelium-dependent relaxation was assessed by constructing cumulative concentration-response curves to acetylcholine (ACh, 0.001–10 μmol/l) during phenylephrine (10 μmol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-α resulted in significant blunted maximal relaxing responses ( Emax) to ACh compared with untreated rings (22 ± 4 vs. 82 ± 3%, respectively). IL-10 knockout mice treated with TNF-α showed significant impairment in ACh responses ( Emax) compared with C57BL/6 mice treated with TNF-α (51 ± 3 vs. 72 ± 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-α in in vitro and in vivo experiments, whereas IL-10 restored the eNOS expression. In conclusion, the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation caused by TNF-α by protecting eNOS expression.

327 UNSATURATED AND SATURATED NON-ESTERIFIED FATTY ACIDS DIFFERENTLY AFFECT LIPID STORAGE AND DEVELOPMENTAL COMPETENCE OF BOVINE OOCYTES

2010 ◽  
Vol 22 (1) ◽  
pp. 319
Author(s):  
H. Aardema ◽  
P. Vos ◽  
H. Knijn ◽  
B. Roelen ◽  
B. Gadella
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Palmitic Acid ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Post Partum ◽  
Developmental Competence ◽  
Negative Effects ◽  
Esterified Fatty Acids

Fertility in high-producing dairy cows has declined over the last decades. An increased serum and follicular fluid concentration of non-esterified fatty acids (NEFAs), due to body fat mobilization in the early post partum period, has been postulated as a cause for this fertility decline. NEFA concentrations and composition may change in the environment of the oocyte and thus might affect the storage depots of esterified NEFAs in the oocyte. We exposed COCs to unsaturated (oleic acid) or saturated (palmitic acid) NEFAs during maturation and subsequently examined lipid droplets and developmental competence of the oocytes. COCs from 3-8 mm follicles of slaughterhouse ovaries were cultured in control maturation medium (TCM-199) and medium containing 100, 250, or 500 μM oleic and/or palmitic acid (10 mM fatty acid was bound to 10% BSA fatty acid free). These concentrations were based on in vivo measured NEFA concentrations in follicular fluid in the early post partum period (Leroy et al. 2005 Reproduction 130, 485-495). After 23 h of maturation, COCs were fertilized (450 per group) and cultured till the blastocyst stage, or fixed (80 per group) for lipid droplet staining with C1-BODIPY® 500/510 C12. Confocal microscopy was performed to determine lipid droplet size in (im(mean) and the number of lipid droplets per oocyte. Lipid droplet number and the log of size were analyzed using analysis of variances with condition as fixed factor. Variation was described as the standard error of the mean. Similar concentrations of palmitic or oleic acid had an opposite effect on the size of lipid droplets in oocytes. The number of lipid droplets dramatically decreased in oocytes exposed to 500 μM palmitic acid (178 ± 20), whereas the number increased after exposure to 500 μM oleic acid (554 ± 15). The number of lipid droplets of oocytes exposed to a combination of 250 μM palmitic acid and 250 μM oleic acid (421 ± 23) was comparable with the control and lower oleic and palmitic acid concentrations. Exposure of COCs to palmitic acid during maturation resulted in reduced blastocyst development in a dose-dependent manner (from 18 ± 1.4%, 13 ± 2.4% to 2.8 ± 1.3% after exposure to 500 μM) when compared to control (20 ± 2.2%) or oocytes exposed to oleic acid (from 23 ± 1.6%, 23 ± 3.3% till 28 ± 3.3%). Negative effects of palmitic acid were counteracted by simultaneous exposure to oleic acid during in vitro oocyte maturation (26 ± 5.5%). We conclude that palmitic acid elicited negative effects on early embryonic development, possibly because it induces a reduction in the number of lipid droplets. These adverse effects can be offset by oleic acid during maturation. Moreover a high oleic acid concentration increased the number and size of lipid droplets of oocytes. The regulatory pathways involved in the noted differences in lipid storage features of in vitro-matured oocytes as well as the adverse effects of palmitic acid on early embryonic development are currently under research.

Inhibition of binding of gonadal steroids to serum binding proteins by non-esterified fatty acids: the influence of chain length and degree of unsaturation

1989 ◽  
Vol 120 (2) ◽  
pp. 175-179 ◽  
Author(s):  
C. Street ◽  
R. J. S. Howell ◽  
L. Perry ◽  
S. Al-Othman ◽  
T. Chard
Keyword(s):  
Fatty Acids ◽  
Protein Binding ◽  
Unsaturated Fatty Acids ◽  
Late Pregnancy ◽  
Sex Hormone Binding Globulin ◽  
Partial Purification ◽  
Normal Female ◽  
Esterified Fatty Acids ◽  
Vitro Binding

Abstract. The effect of non-esterified fatty acids (NEFA) on the in vitro binding of testosterone, 5-alpha dihydrotestosterone and estradiol E2 to sex hormone binding globulin (SHBG) was examined using pooled normal female serum, and SHBG and albumin fractions obtained from the partial purification of late pregnancy serum. A range of saturated and unsaturated fatty acids were examined for their effect on steroid-protein binding. In normal female serum, NEFA added at physiological concentrations disrupted steroid-protein binding. The shorter chain (C8–C12) saturated acids and the poly-unsaturated acids proved to be more effective inhibitors than the longer chain saturated or mono-unsaturated acids. The greatest inhibition was obtained with E2 whereas the binding of dihydrotestosterone was least affected. With partially purified SHBG, the same concentrations of NEFA were less effective at inhibiting the binding of dihydrotestosterone and testosterone but elicited the same effect with E2. The binding of steroids to albumin appeared to be unaffected by these concentrations of NEFA.

THE DIAGNOSIS OF HYPOPITUITARISM WITH SPECIAL REFERENCE TO THE ESTIMATION OF PLASMA NON-ESTERIFIED FATTY ACIDS

1970 ◽  
Vol 46 (2) ◽  
pp. 167-175 ◽  
Author(s):  
R. WILKINSON ◽  
R. HALL ◽  
A. COOPER ◽  
D. J. NEWELL
Keyword(s):  
Fatty Acids ◽  
Growth Hormone ◽  
No Value ◽  
Insulin Injection ◽  
Thyroid Stimulating Hormone ◽  
Adrenocorticotrophic Hormone ◽  
Plasma Nefa ◽  
Esterified Fatty Acids ◽  
Significant Impairment ◽  
Sugar Levels

SUMMARY Plasma non-esterified fatty acid (NEFA) levels during a standard insulin sensitivity test have been compared in hypopituitary and hospital control patients who had undergone full routine pituitary investigations. Significant impairment of the recovery of plasma NEFA levels after insulin injection was found in the hypopituitary group as a whole, but this finding was not consistent in individual cases. It is concluded that the measurement of NEFA levels is of little value in the diagnosis of mild hypopituitarism. Blood sugar levels after insulin were of no value in the diagnosis of minor degrees of hypopituitarism. In 19 patients with mild hypopituitarism the order of frequency of deficiency of individual hormones, as judged by tests currently available, was gonadotrophins followed by growth hormone, adrenocorticotrophic hormone, thyroid-stimulating hormone, and antidiuretic hormone.

Palmitic acid uptake by the rat soleus muscle in vitro

2001 ◽  
Vol 79 (4) ◽  
pp. 419-424 ◽  
Author(s):  
M Górecka ◽  
M Synak ◽  
L Budohoski ◽  
J Langfort ◽  
S Moskalewski ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Soleus Muscle ◽  
Fatty Acid Uptake ◽  
Cellular Fatty Acid ◽  
Acid Uptake ◽  
Acid Complex ◽  
Rat Soleus Muscle

The rate of fatty acid uptake, oxidation, and deposition in skeletal muscles in relation to total and unbound to albumin fatty acids concentration in the medium were investigated in the incubated rat soleus muscle. An immunohistochemical technique was applied to demonstrate whether the albumin-bound fatty acid complex from the medium penetrates well within all areas of the muscle strips. It was found that the percentage of incorporation of palmitic acid into intramuscular lipids was fairly constant, independently of the fatty acid concentration in the medium, and amounted to 63–72% for triacylglycerols, 7–12% for diacylglycerols-monoacylglycerols, and 19–26% for phospholipids. Both palmitic acid incorporation into the muscle triacylglycerol stores and its oxidation to CO2closely correlated with an increase in both total and unbound to albumin fatty acid concentrations in the incubation medium. Under conditions of increased total but constant unbound to albumin palmitic acid concentrations, the incorporation of palmitic acid into triacylglycerols and its oxidation to CO2were also increased, but to a lower extent. This supports the hypothesis that the cellular fatty acid metabolism depends not only on the availability of fatty acids unbound to albumin, but also on the availability of fatty acids complexed to albumin.Key words: skeletal muscle, fatty acids, triacylglycerols, phospholipids.

Inhaled nitric oxide prevents pulmonary endothelial dysfunction after mesenteric ischemia-reperfusion

1996 ◽  
Vol 271 (2) ◽  
pp. L326-L331 ◽  
Author(s):  
D. A. Fullerton ◽  
J. H. Eisenach ◽  
R. C. McIntyre ◽  
R. S. Friese ◽  
B. C. Sheridan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Inhaled Nitric Oxide ◽  
Neutrophil Accumulation ◽  
Response Curves ◽  
Significant Impairment ◽  
Inhaled No

This study examined the effect of inhaled nitric oxide (NO) on lung neutrophil accumulation and endothelial-dependent and -independent guanosine 3',5'-cyclic monophosphate (cGMP)-mediated mechanisms of pulmonary vasorelaxation after mesenteric ischemia-reperfusion (I/R) in mechanically ventilated rats. Inhaled NO (20 ppm) was administered in two protocols: 1) throughout mesenteric I/R and 2) during mesenteric reperfusion alone. Concentration-response curves were generated (10(-9) to 10(-8) M) for acetylcho-line (ACh), A23187, and sodium nitroprusside (SNP) in isolated pulmonary arterial rings preconstricted with phenylephrine. Lung neutrophil accumulation [myeloperoxidase assay (MPO)] was significantly increased from 2.4 +/- 0.2 units/g lung wt in controls to 10.3 +/- 0.4 after 1 h of superior mesenteric artery occlusion and 2 h of reperfusion. Lung MPO activity was not different from controls in rats receiving inhaled NO either 1) during mesenteric I/R or during mesenteric reperfusion alone. The concentration-response curves demonstrated significant impairment of pulmonary vasorelaxation by endothelial-dependent mechanisms (response to ACh and A23187) but not endothelial-independent pulmonary vasorelaxation (response to SNP) after mesenteric I/R. This pulmonary vasomotor dysfunction was prevented by administration of inhaled NO during either mesenteric I/R or during mesenteric reperfusion alone. We conclude that inhaled NO prevents lung neutrophil accumulation and pulmonary vascular endothelial dysfunction after mesenteric I/R.

scholarly journals Diagnóstico in vitro de la deficiencia LCHAD; /In vitro diagnosis of LCHAD deficiency

2013 ◽  
Vol 13 (1) ◽  
pp. 24-30
Author(s):  
José Henry Osorio
Keyword(s):  
Fatty Acids ◽  
Palmitic Acid ◽  
Oxidation Rate ◽  
Lchad Deficiency ◽  
In Vitro Diagnosis

Objetivo. Analizar la oxidación de sustratos deuterados en fibroblastos de pacientes que sufren deficiencia de hidroxiacil-coa deshidrogenasa (lchad).Materiales y métodos: fibroblastos de pacientes y controles se incubaron con ácido palmíticodeuterado y se determinaron los intermediarios de la oxidación del mismo en nmol/mg proteína/72 horasResultados: las concentraciones observadas para los diferentes ácidos grasos, permiten diferenciar los fibroblastos de pacientes con deficiencia de lchad de los fibroblastos controles Conclusión: esta técnica permite el diagnóstico in vitro de la deficiencia de hidroxi-acil-coa de cadena larga. objective: to analyse the oxidation rate of tritiated substrates in fibroblasts of patientssuffering the deficiency and controls.materials and methods: fibroblasts from patients and controls were incubated withdeuterated palmític acid and the metabolites of the oxidation of this substrate weremeasured in nmol/mg proteína/72 hours.results: the observed concentrations for different fatty acids, enable us to differentiatefibroblasts of patients suffering lchad deficiency from normal fibroblasts.conclusion: a characteristic profile for this deficiency was found using this techniquewhich its in vitro diagnosis.

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