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1.
Nutrients ; 12(2)2020 Feb 18.
Article in English | MEDLINE | ID: mdl-32085385

ABSTRACT

Osteoarthritis (OA) is a degenerative condition of joints, causing pain and swelling, and can be caused or worsened by trauma and obesity. The objectives of this study were to determine whether pain behaviour and progression of OA were increased in rats with trauma-induced OA fed dietary saturated fatty acids (SFA). Male Wistar rats were fed either a corn starch diet (C) or high-carbohydrate high-fat diet (H) with either 20% beef tallow or SFA (lauric (HLA), myristic (HMA), palmitic (HPA) or stearic (HSA) acids) for 16 weeks prior to and 8 weeks after excision of the medial meniscus of right knee joint to initiate OA when pain behaviour, glial activity, progression of knee OA, inflammatory mediators and signs of metabolic syndrome were assessed. Rats fed beef tallow, palmitic or stearic acids showed increased pain symptoms characterised by decreased hind paw/limb withdrawal thresholds and grip strengths and increased spinal astrogliosis and microgliosis compared to rats fed lauric or myristic acids. However, the severity of OA joint damage was unchanged by these dietary manipulations. We conclude that pain symptoms of trauma-induced OA in rats worsen with increased dietary beef tallow or palmitic or stearic acids, but improve with lauric or myristic acids, despite unchanged OA cartilage damage.


Subject(s)
Dietary Fats/adverse effects , Fats/adverse effects , Fatty Acids/adverse effects , Knee Injuries/complications , Osteoarthritis, Knee/etiology , Pain/diet therapy , Pain/etiology , Animals , Diet, High-Fat , Dietary Carbohydrates , Disease Progression , Fatty Acids/administration & dosage , Lauric Acids/administration & dosage , Male , Myristic Acid/administration & dosage , Palmitic Acid/adverse effects , Rats, Wistar , Stearic Acids/adverse effects
2.
Int J Pharm ; 532(1): 21-28, 2017 Oct 30.
Article in English | MEDLINE | ID: mdl-28864392

ABSTRACT

Splice-switching antisense oligonucleotides (SSOs) are emerging therapeutics with two SSOs recently approved by the FDA for Duchenne muscular dystrophy and spinal muscular atrophy. SSOs are administered without any delivery vector and require large doses to achieve the therapeutic benefit, primarily due to their poor cellular uptake. Although cell-penetrating peptides (CPP) have shown great potential in delivering SSOs into cells, their capacity as delivery vector is limited. Here we have studied the effect of lipid conjugation on the cell permeability of a known CPP (ApoE). Myristic acid was coupled at the N-terminus of ApoE to a C-terminal cysteine residue. The myristoylated ApoE (Myr-ApoE) was conjugated to a maleimide functionalised phosphorodiamidate morpholino oligonucleotide (PMO). The Myr-ApoE-PMO conjugate showed no cytoxicity and had significantly higher efficiency in cell permeability with 30% higher splice-switching activity compared to ApoE-PMO. The self-assembly properties of this amphiphilic lipopeptide-PMO conjugate was assessed. Transmission electron microscopy showed formation of nanoparticles with amphiphile behaviour and spherical structure. The self-assembly of Myr-ApoE-PMO into nanoparticles enabled it to better bind to cell membranes and to be more efficiently taken up by fibroblast cells. These results showed that modification of physico-chemical properties of peptides to produce peptide amphiphiles enhances cellular uptake and can be used as an efficient delivery vector for therapeutic SSOs.


Subject(s)
Apolipoproteins E , Lipopeptides , Morpholinos , Myristic Acid , Nanoparticles , Apolipoproteins E/administration & dosage , Apolipoproteins E/chemistry , Biological Transport , Cell Survival/drug effects , Cells, Cultured , Fibroblasts/drug effects , Humans , Lipopeptides/administration & dosage , Lipopeptides/chemistry , Morpholinos/administration & dosage , Morpholinos/chemistry , Muscular Atrophy, Spinal , Myristic Acid/administration & dosage , Myristic Acid/chemistry , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Survival of Motor Neuron 2 Protein/genetics
3.
Biomed Res Int ; 2017: 8798546, 2017.
Article in English | MEDLINE | ID: mdl-29392140

ABSTRACT

Fatty acids (C6-C18) found in human amniotic fluid, colostrum, and maternal milk reduce behavioral indicators of experimental anxiety in adult Wistar rats. Unknown, however, is whether the anxiolytic-like effects of fatty acids provide a natural mechanism against anxiety in young offspring. The present study assessed the anxiolytic-like effect of a mixture of lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, elaidic acid, and linoleic acid in Wistar rats on postnatal day 28. Infant rats were subjected to the elevated plus maze, defensive burying test, and locomotor activity test. Diazepam was used as a reference anxiolytic drug. A group that was pretreated with picrotoxin was used to explore the participation of γ-aminobutyric acid-A (GABAA) receptors in the anxiolytic-like effects. Similar to diazepam, the fatty acid mixture significantly increased the frequency of entries into and time spent on the open arms of the elevated plus maze and decreased burying behavior in the defensive burying test, without producing significant changes in spontaneous locomotor activity. These anxiolytic-like effects were blocked by picrotoxin. Results suggest that these fatty acids that are contained in maternal fluid may reduce anxiety-like behavior by modulating GABAergic neurotransmission in infant 28-day-old rats.


Subject(s)
Anti-Anxiety Agents/administration & dosage , Anxiety Disorders/drug therapy , Fatty Acids/administration & dosage , Maze Learning/drug effects , Animals , Anti-Anxiety Agents/chemistry , Anxiety Disorders/physiopathology , Diazepam/administration & dosage , Fatty Acids/chemistry , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Monounsaturated/chemistry , Humans , Lauric Acids/administration & dosage , Lauric Acids/chemistry , Linoleic Acid/administration & dosage , Linoleic Acid/chemistry , Maze Learning/physiology , Motor Activity/drug effects , Motor Activity/physiology , Myristic Acid/administration & dosage , Myristic Acid/chemistry , Oleic Acid/administration & dosage , Oleic Acid/chemistry , Oleic Acids , Palmitic Acid/administration & dosage , Palmitic Acid/chemistry , Rats , Receptors, GABA-A , Stearic Acids/administration & dosage , Stearic Acids/chemistry
4.
Meat Sci ; 121: 88-95, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27288901

ABSTRACT

Replacement of soybean meal by peanut cake was evaluated on the meat quality of 45 Dorper × Santa Inês crossbred lambs. Animals were distributed in a completely randomized design, with five treatments and nine repetitions, and fed Tifton-85 hay and a concentrate mixed with 0.0%, 25.0%, 50.0%, 75.0% or 100.0% peanut cake based on the dry mass of the complete diet. The longissimus lumborum muscle was used to determine the proximate composition, physical-chemical characteristics and fatty acid profile. Significant differences (P<0.05) were found for the crude protein and ether extract levels, with average values of 23.38% and 2.15% in the sheep meat, respectively. The physical-chemical characteristics of the loin were not affected (P>0.05) by the diets. The fatty acid profile was affected by peanut cake supplementation for myristic, myristoleic, palmitoleic, linolenic and arachidonic fatty acids. Peanut cake can be added in the diet of lambs no effect on physical-chemical characteristics. However, the total replacement of the soybean meal altered the proximate composition and fatty acid profile of the meat.


Subject(s)
Animal Feed/analysis , Diet/veterinary , Red Meat/analysis , Animal Nutritional Physiological Phenomena , Animals , Arachidonic Acid/administration & dosage , Arachis/chemistry , Chemical Phenomena , Fatty Acids/analysis , Fatty Acids, Monounsaturated/administration & dosage , Linolenic Acids/administration & dosage , Male , Myristic Acid/administration & dosage , Sheep, Domestic
5.
Peptides ; 62: 176-82, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25453979

ABSTRACT

We have previously described the pharmacokinetics of mouse [D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, following delivery by subcutaneous (SC), intraperitoneal (IP), and intramuscular (IM) injection, and by oral gavage and intranasal instillation. These profiles suggested that the observed efficacy of [D-Leu-4]-OB3 on energy balance, glycemic control, and bone turnover in ob/ob and db/db mice might be improved by efforts directed toward improving its bioavailability, i.e., increasing maximum uptake (Cmax), extending serum half-life (t½), and reducing plasma clearance (CL). To address these issues, myristic (tetradecanoic) acid was conjugated to the N-terminal of [D-Leu-4]-OB3 (designated MA-[D-Leu-4]-OB3), and the pharmacokinetics of MA-[D-Leu-4]-OB3 in male Swiss Webster mice following SC, IP, and IM injection in PBS, and by oral and intranasal delivery in dodecyl maltoside (DDM, trade name Intravail®), a transmucosal absorption enhancing agent, were compared to those of [D-Leu-4]-OB. At a dose of MA-[D-Leu-4]-OB3 10-fold lower than that used previously for [D-Leu-4]-OB3 (0.1 mg vs.1.0 mg, respectively), Cmax of MA-[D-Leu-4]-OB3 was 11.1-, 7.5-, 1.9-, and 1.7-fold higher, t1/2 was 3.5-, 5.0-, 9.1-, and 86.7-fold longer, and CL was 17.0-, 11.6-, 5.7-, and 5.0-fold slower than [D-Leu-4]-OB3 following SC, IP, IM, and oral delivery, respectively. Furthermore, in leptin-resistant obese male db/db mice, oral delivery of MA-[D-Leu-4]-OB3 in DDM at concentrations up to 10-fold lower than those used with [D-Leu-4]-OB3 reduced fasting blood glucose levels in a dose-related manner.


Subject(s)
Diabetes Mellitus/drug therapy , Myristic Acid/administration & dosage , Obesity/drug therapy , Peptide Fragments/administration & dosage , Animals , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Humans , Leptin/chemical synthesis , Leptin/genetics , Male , Mice , Mice, Inbred NOD , Mice, Obese , Myristic Acid/chemical synthesis , Obesity/metabolism , Obesity/pathology , Peptide Fragments/chemical synthesis , Peptides/administration & dosage , Peptides/chemical synthesis , Pharmacokinetics
6.
Biomed Res Int ; 2014: 492141, 2014.
Article in English | MEDLINE | ID: mdl-25328885

ABSTRACT

A mixture of eight fatty acids (linoleic, palmitic, stearic, myristic, elaidic, lauric, oleic, and palmitoleic acids) at similar concentrations identified in human amniotic fluid produces anxiolytic-like effects comparable to diazepam in Wistar rats. However, individual effects of each fatty acid remain unexplored. In Wistar rats, we evaluated the separate action of each fatty acid at the corresponding concentrations previously found in human amniotic fluid on anxiety-like behaviour. Individual effects were compared with vehicle, an artificial mixture of the same eight fatty acids, and a reference anxiolytic drug (diazepam, 2 mg/kg). Myristic acid, the fatty acid mixture, and diazepam increased the time spent in the open arms of the elevated plus maze and reduced the anxiety index compared with vehicle, without altering general locomotor activity. The other fatty acids had no effect on anxiety-like behaviour, but oleic acid reduced locomotor activity. Additionally, myristic acid produced anxiolytic-like effects only when the concentration corresponded to the one identified in human amniotic fluid (30 µg/mL) but did not alter locomotor activity. We conclude that of the eight fatty acids contained in the fatty acid mixture, only myristic acid produces anxiolytic-like effects when administered individually at a similar concentration detected in human amniotic fluid.


Subject(s)
Amniotic Fluid/chemistry , Anti-Anxiety Agents/administration & dosage , Anxiety/prevention & control , Anxiety/physiopathology , Fatty Acids/administration & dosage , Maze Learning/drug effects , Myristic Acid/administration & dosage , Animals , Dose-Response Relationship, Drug , Fatty Acids/chemistry , Humans , Male , Myristic Acid/chemistry , Rats , Rats, Wistar , Treatment Outcome
7.
Pharmacol Biochem Behav ; 122: 228-33, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24726705

ABSTRACT

Although bone cancer pain is a common intractable clinical symptom, its underlying mechanisms are still elusive. Accumulating evidence reveals that the N-methyl-D-aspartate (NMDA) receptor containing a 2B subunit (NR2B) in the spinal cord contributes to bone cancer pain. Our preliminary study demonstrated that intrathecal injection of fusion peptide Myr-RC-13 could disrupt spinal KIF17/mLin10 interaction, which is an essential component of KIF17-mediated NR2B transport. Here we report a means by infusion of the selected peptide Myr-RC-13 intrathecally to attenuate bone cancer pain. The results showed that inoculation of fibrosarcoma NCTC 2472 cells into the femur cavity of C3H/HeJ mice induced progressive bone cancer pain and resulted in up-regulation of KIF17 and NR2B in the spinal cord. In addition, repetitive spinal delivery of Myr-RC-13 relieved bone cancer-related mechanical allodynia and spontaneous pain behaviors, and down-regulated expression of spinal KIF17 and NR2B. Finally, our results demonstrated that selected peptide Myr-RC-13 was able to attenuate bone cancer pain via decreasing spinal KIF17 and NR2B expressions. Therefore, selected peptide Myr-RC-13 might be a potential analgesic strategy for bone cancer pain.


Subject(s)
Bone Neoplasms/drug therapy , Gene Expression Regulation, Neoplastic , Kinesins/antagonists & inhibitors , Pain/prevention & control , Peptide Fragments/administration & dosage , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Animals , Bone Neoplasms/complications , Bone Neoplasms/metabolism , Injections, Spinal , Kinesins/biosynthesis , Male , Mice , Mice, Inbred C3H , Myristic Acid/administration & dosage , Oligopeptides/administration & dosage , Oligopeptides/genetics , Pain/etiology , Pain/metabolism , Pain Measurement/drug effects , Pain Measurement/methods , Peptide Fragments/genetics , Random Allocation , Receptors, N-Methyl-D-Aspartate/biosynthesis , Tumor Cells, Cultured , Xenograft Model Antitumor Assays/methods
8.
Nutrition ; 29(6): 892-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23594583

ABSTRACT

OBJECTIVE: Evidence on the relation of saturated fatty acids (SFA) with inflammatory markers and adipokines is scarce and inconsistent. This study aimed to evaluate the association of the intake of total SFA, their subtypes (lauric, myristic, palmitic, and stearic acids), and SFA to polyunsaturated fatty acids (PUFA) ratio (SFA/PUFA ratio) with serum concentrations of high-sensitivity C-reactive protein (hs-CRP), adiponectin, and leptin among Portuguese adults. METHODS: We studied 395 non-institutionalized inhabitants of Porto (52.2% women; age range: 26-64 y) who were evaluated in 2010-2011, as part of EPIPorto study. Fatty acids intake was assessed with a validated semi-quantitative food frequency questionnaire. Blood was sampled after an overnight fast and serum concentrations of hs-CRP (through particle-enhanced immunonephelometry), adiponectin, and leptin (through radioimmunoassay) were determined. Regression coefficients (ß) and 95% confidence intervals (CI) were obtained from linear regression models, stratified by sex. RESULTS: After adjusting for age, education, regular physical exercise, smoking, and central body fat percentage, hs-CRP was significantly and positively associated with lauric (ß = 0.218; 95% CI, 0.071-0.365) and myristic acids (ß = 0.220; 95% CI, 0.073-0.368) and with SFA/PUFA ratio (ß = 0.171; 95% CI, 0.022-0.320) in men, but not in women. For adiponectin and leptin, no significant associations with SFA intake were observed in either sex. CONCLUSIONS: A detrimental role of lauric and myristic acids and of high SFA/PUFA ratio is suggested by their association with elevated hs-CRP concentrations in men. Our findings may be helpful in the planning of dietary modifications aimed at the modulation of inflammatory activity that could be an intermediate step to coronary events.


Subject(s)
Adiponectin/blood , C-Reactive Protein/metabolism , Fatty Acids/administration & dosage , Leptin/blood , Absorptiometry, Photon , Adult , Biomarkers/blood , Dietary Fats/administration & dosage , Fatty Acids/blood , Fatty Acids, Unsaturated/administration & dosage , Female , Humans , Lauric Acids/administration & dosage , Male , Middle Aged , Myristic Acid/administration & dosage , Nutrition Assessment , Portugal , Prospective Studies , Socioeconomic Factors , Surveys and Questionnaires , Young Adult
9.
J Dairy Sci ; 94(3): 1445-54, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21338809

ABSTRACT

Two experiments were conducted to assess the effects of a mixture of dietary additives on enteric methane production, rumen fermentation, diet digestibility, energy balance, and animal performance in lactating dairy cows. Identical diets were fed in both experiments. The mixture of feed additives investigated contained lauric acid, myristic acid, linseed oil, and calcium fumarate. These additives were included at 0.4, 1.2, 1.5, and 0.7% of dietary dry matter, respectively (treatment ADD). Experimental fat sources were exchanged for a rumen inert source of fat in the control diet (treatment CON) to maintain isolipidic rations. Cows (experiment 1, n=20; experiment 2, n=12) were fed restricted amounts of feed to avoid confounding effects of dry matter intake on methane production. In experiment 1, methane production and energy balance were studied using open-circuit indirect calorimetry. In experiment 2, 10 rumen-fistulated animals were used to measure rumen fermentation characteristics. In both experiments animal performance was monitored. The inclusion of dietary additives decreased methane emissions (g/d) by 10%. Milk yield and milk fat content tended to be lower for ADD in experiment 1. In experiment 2, milk production was not affected by ADD, but milk fat content was lower. Fat- and protein-corrected milk was lower for ADD in both experiments. Milk urea nitrogen content was lowered by ADD in experiment 1 and tended to be lower in experiment 2. Apparent total tract digestibility of fat, but not that of starch or neutral detergent fiber, was higher for ADD. Energy retention did not differ between treatments. The decrease in methane production (g/d) was not evident when methane emission was expressed per kilogram of milk produced. Feeding ADD resulted in increases of C12:0 and C14:0 and the intermediates of linseed oil biohydrogenation in milk in both experiments. In experiment 2, ADD-fed cows tended to have a decreased number of protozoa in rumen fluid when compared with that in control cows. Total volatile fatty acid concentrations were lower for ADD, whereas molar proportions of propionate increased at the expense of acetate and butyrate.


Subject(s)
Cattle/physiology , Diet/veterinary , Digestion/drug effects , Food Additives/pharmacology , Lactation/drug effects , Methane/biosynthesis , Animal Feed , Animals , Cattle/metabolism , Energy Metabolism/drug effects , Female , Fermentation/drug effects , Food Additives/administration & dosage , Fumarates/administration & dosage , Fumarates/pharmacology , Lauric Acids/administration & dosage , Lauric Acids/pharmacology , Linseed Oil/administration & dosage , Linseed Oil/pharmacology , Myristic Acid/administration & dosage , Myristic Acid/pharmacology , Rumen/metabolism
10.
J Am Coll Nutr ; 30(6): 511-21, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22331686

ABSTRACT

OBJECTIVE: Saturated fats increase total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) and are linked to coronary artery disease risk. The effect of variance in chain length of saturated fatty acids (SFA) on coronary artery disease in human postprandial lipemia is not well elucidated. METHODS: A total of 20 healthy volunteers were challenged with 3 test meals, similar in fat content (~31% en) but varying in saturated SFA content and polyunsaturated/saturated fatty acid ratios (P/S). The 3 meals were lauric + myristic acid-rich (LM), P/S 0.19; palmitic acid-rich (POL), P/S 0.31; and stearic acid-rich (STE), P/S 0.22. Blood was sampled at fasted baseline and 2, 4, 5, 6, and 8 hours. Plasma lipids (triacylglycerol [TAG]) and lipoproteins (TC, LDL-C, high density lipoprotein-cholesterol [HDL-C]) were evaluated. RESULTS: Varying SFA in the test meal significantly impacted postprandial TAG response (p < 0.05). Plasma TAG peaked at 5 hours for STE, 4 hours for POL, and 2 hours for LM test meals. Area-under-the-curve (AUC) for plasma TAG was increased significantly after STE treatment (STE > LM by 32.2%, p = 0.003; STE > POL by 27.9%, p = 0.023) but was not significantly different between POL and LM (POL > LM by 6.0%, p > 0.05). At 2 hours, plasma HDL-C increased significantly after the LM and POL test meals compared with STE (p < 0.05). In comparison to the STE test meal, HDL-C AUC was elevated 14.0% (p = 0.005) and 7.6% (p = 0.023) by the LM and POL test meals, respectively. The TC response was also increased significantly by LM compared with both POL and STE test meals (p < 0.05). CONCLUSIONS: Chain length of saturates clearly mediated postmeal plasma TAG and HDL-C changes.


Subject(s)
Dietary Fats/administration & dosage , Fatty Acids/administration & dosage , Hyperlipidemias/metabolism , Postprandial Period , Adult , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coconut Oil , Corn Oil/administration & dosage , Corn Oil/chemistry , Cross-Over Studies , Diet , Dietary Fats/adverse effects , Fasting/blood , Female , Humans , Lauric Acids/administration & dosage , Male , Myristic Acid/administration & dosage , Palm Oil , Palmitic Acid/administration & dosage , Plant Oils/administration & dosage , Plant Oils/chemistry , Risk Management , Stearic Acids/administration & dosage , Triglycerides/blood , Young Adult
11.
Am J Physiol Regul Integr Comp Physiol ; 299(5): R1306-16, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20811010

ABSTRACT

Lung surfactant mainly comprises phosphatidylcholines (PC), together with phosphatidylglycerols and surfactant proteins SP-A to SP-D. Dipalmitoyl-PC (PC16:0/16:0), palmitoylmyristoyl-PC (PC16:0/14:0), and palmitoylpalmitoleoyl-PC (PC16:0/16:1) together comprise 75-80% of surfactant PC. During alveolarization, which occurs postnatally in the rat, PC16:0/14:0 reversibly increases at the expense of PC16:0/16:0. As lipoproteins modify surfactant metabolism, we postulated an extrapulmonary origin of PC16:0/14:0 enrichment in surfactant. We, therefore, fed rats (d19-26) with trilaurin (C12:0(3)), trimyristin (C14:0(3)), tripalmitin (C16:0(3)), triolein (C18:1(3)) or trilinolein (C18:2(3)) vs. carbohydrate diet to assess their effects on surfactant PC composition and surface tension function using a captive bubble surfactometer. Metabolism was assessed with deuterated C12:0 (ω-d(3)-C12:0) and ω-d(3)-C14:0. C14:0(3) increased PC16:0/14:0 in surfactant from 12 ± 1 to 45 ± 3% and decreased PC16:0/16:0 from 47 ± 1 to 29 ± 2%, with no impairment of surface tension function. Combined phospholipase A(2) assay and mass spectrometry revealed that 50% of the PC16:0/14:0 peak comprised its isomer 1-myristoyl-2-palmitoyl-PC (PC14:0/16:0). While C12:0(3) was excluded from incorporation into PC, it increased PC16:0/14:0 as well. C16:0(3), C18:1(3), and C18:2(3) had no significant effect on PC16:0/16:0 or PC16:0/14:0. d(3)-C14:0 was enriched in lung PC, either via direct supply or via d(3)-C12:0 elongation. Enrichment of d(3)-C14:0 in surfactant PC contrasted its rapid turnover in plasma and liver PC, where its elongation product d(3)-C16:0 surmounted d(3)-C14:0. In summary, high surfactant PC16:0/14:0 during lung development correlates with C14:0 and C12:0 supply via specific C14:0 enrichment into lung PC. Surfactant that is high in PC16:0/14:0 but low in PC16:0/16:0 is compatible with normal respiration and surfactant function in vitro.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine/metabolism , Dietary Fats/metabolism , Lung/metabolism , Myristic Acid/metabolism , Pulmonary Surfactants/metabolism , Animals , Chromatography, Gas , Chromatography, High Pressure Liquid , Deuterium , Dietary Carbohydrates/administration & dosage , Dietary Carbohydrates/metabolism , Dietary Fats/administration & dosage , Female , Lung/growth & development , Male , Myristic Acid/administration & dosage , Phospholipases A2/metabolism , Rats , Rats, Sprague-Dawley , Respiration , Spectrometry, Mass, Electrospray Ionization , Surface Tension , Tandem Mass Spectrometry , Time Factors , Triglycerides/administration & dosage , Triglycerides/metabolism , Triolein/administration & dosage , Triolein/metabolism
12.
Eur J Clin Nutr ; 64(10): 1065-71, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20664620

ABSTRACT

OBJECTIVES: To study the relationship between lipid, fatty acid and lipid-rich food intake and current asthma in a group of Spanish schoolchildren. SUBJECTS/METHODS: The subjects of this cross-sectional study were 638 Spanish schoolchildren (8-13 years of age). The weight and height of all the subjects were recorded. A questionnaire, completed by the subjects' parents, was used to obtain personal and health information. Current asthma was established when the children had ever had asthma, if they had been diagnosed with asthma by a doctor and if they had been treated with medications at some time in the previous 12 months. Food intake was monitored using a 3-day food record. All foods consumed were converted into energy and nutrients. RESULTS: The energy derived from lipids, saturated fatty acids (SFAs) and myristic and palmitic acids was independently associated with current asthma (Odds Ratio (OR) third tertile 2.85 (1.01-8.07) P=0.049, 10.00 (0.89-111.97) P=0.002, 11.21 (1.36-92.24) P=0.002, 7.58 (1.40-41.03) P=0.022, respectively), as was the intake of butter (OR third tertile 2.97 (1.01-8.68) P=0.001). No relationship was seen between this condition and the intake of any other fatty acid, the n-6/n-3 ratio, nor the consumption of margarine, milk products, fish, meat, eggs or vegetable oils. CONCLUSIONS: Increased intakes of SFAs, myristic and palmitic acids and butter seem to be related to the risk of current asthma in children.


Subject(s)
Asthma/epidemiology , Dietary Fats/administration & dosage , Adolescent , Body Mass Index , Butter/adverse effects , Child , Cross-Sectional Studies , Diet/adverse effects , Diet Records , Dietary Fats/adverse effects , Energy Intake , Female , Humans , Male , Myristic Acid/administration & dosage , Myristic Acid/adverse effects , Palmitic Acid/administration & dosage , Palmitic Acid/adverse effects , Parents , Prevalence , Spain/epidemiology , Surveys and Questionnaires
13.
Eur J Pharmacol ; 626(2-3): 262-5, 2010 Jan 25.
Article in English | MEDLINE | ID: mdl-19786012

ABSTRACT

Numerous plants have proven to improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with benign prostatic hyperplasia. Major components of those plants were lauric acid and myristic acid. Our study investigated whether lauric acid or myristic acid prevent testosterone induced prostatic hyperplasia in rats. Rats were divided into negative control and testosterone induced prostatic hyperplasia rats (positive control, low dose lauric acid treated, high dose lauric acid treated, low dose of myristic acid treated, high dose of myristic acid treated, finasteride treated). Testosterone and drug treatment were carried out for 14 days. Body weights were recorded before and after treatment. On 15th day, rats were sacrificed, prostates were weighed and histopathological studies were carried out. Lauric acid/myristic acid treatment showed significant inhibition of prostate enlargement and protection of histoarchitecture of prostate when compared with positive control group. In conclusion, the study showed that lauric acid/myristic acid reduced the increase of both prostate weight and prostate weight:body weight ratio, markers of testosterone induced prostatic hyperplasia in rats.


Subject(s)
Lauric Acids/pharmacology , Myristic Acid/pharmacology , Prostatic Hyperplasia/chemically induced , Prostatic Hyperplasia/prevention & control , Testosterone/antagonists & inhibitors , Testosterone/pharmacology , Administration, Oral , Animals , Body Weight/drug effects , Lauric Acids/administration & dosage , Male , Myristic Acid/administration & dosage , Organ Size/drug effects , Prostate/drug effects , Prostate/pathology , Prostatic Hyperplasia/pathology , Rats , Rats, Wistar
14.
Lipids ; 42(8): 717-22, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17564735

ABSTRACT

Cholesterol removal from tissues into HDL depends on the activity of lecithin-cholesterol acyltransferase (LCAT; E.C. 2.3.1.43) that is associated with lower cardiovascular diseases risk. HDL cholesterol concentration and LCAT activity can be modulated by dietary fatty acids. Original data with substrate models have shown a positive effect of myristic acid (MA) on the esterification rate of cholesterol. The purpose of this study was to examine the effect of moderate intakes of MA associated with recommended intake of alpha-linolenic acid (ALA) on LCAT activity in humans. Two experimental diets were tested for 3 months each. Diet 1-MA 1.2% of total energy (TE) and ALA 0.9% TE, diet 2-MA 1.8% and ALA 0.9% TE; a control diet (MA 1.2% and ALA 0.4% TE) was given 3 months before diet 1 and diet 2. The endogenous activity of LCAT was determined at completion of each diet. Compared with the control diet (13.2 +/- 3.1 micromol CE/(L x h)), LCAT activity increased significantly (P < 0.001) with diet 1 (24.2 +/- 3.6 micromol CE/(L x h)) and diet 2 (33.3 +/- 7.4 micromol CE/(L x h)); the increase observed with diet 2 was significantly (P < 0.001) greater than that due to diet 1. These results suggest that ALA (from rapeseed oil, mainly in sn-2 position) and MA (from dairy fat, mainly in sn-2 position) favor LCAT activity, by respective increases of 83 and 38%. When they are supplied together, a complementary effect was observed (average increase of 152%). Moreover, these observations were associated with a decrease of the ratio of total to HDL-cholesterol. In conclusion, our results suggest that moderate supply of MA (1.8% TE) associated with the recommended intake of ALA (0.9% TE) contributes to improve LCAT activity.


Subject(s)
Myristic Acid/administration & dosage , Phosphatidylcholine-Sterol O-Acyltransferase/metabolism , alpha-Linolenic Acid/administration & dosage , Adult , Aged , Aged, 80 and over , Dietary Fats/administration & dosage , Dietary Fats/pharmacology , Humans , Lipids/blood , Lipoproteins/blood , Male , Middle Aged , Myristic Acid/pharmacology , Phosphatidylcholine-Sterol O-Acyltransferase/blood , alpha-Linolenic Acid/pharmacology
15.
J Dairy Sci ; 90(4): 1851-8, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17369226

ABSTRACT

The objective of this study was to evaluate the effects of supplementing myristic acid in dairy cow rations on ruminal methanogenesis and the fatty acid profile in milk. Twelve multiparous Holstein dairy cows (710 +/- 17.3 kg of live weight; 290 +/- 41.9 d in milk) housed in a tie-stall facility were used in the study. The cows were paired by parity and days in milk and allocated to 1 of 2 treatments: 1) the regular milking cow total mixed ration (control diet), and 2) the regular milking cow total mixed ration supplemented with 5% myristic acid on a dry matter basis (MA diet). The cows were fed and milked twice daily (feeding, 0830 and 1300 h; milking, 0500 and 1500 h). The experiment was conducted as a completely randomized design and consisted of a 7-d pretrial period when cows were fed the control diet to obtain baseline measurements, a 10-d dietary adaptation period, and a 1-d, 8-h measurement period. The MA diet reduced methane (CH4) production by 36% (608.2 vs. 390.6 +/- 56.46 L/d, control vs. MA diet, respectively) and milk fat percentage by 2.4% (4.2 vs. 4.1 +/- 0.006%, control vs. MA diet, respectively). The MA diet increased 14:0 in milk by 139% and cis-9 14:1 by 195%. There was a correlation (r = -0.58) between the 14:0 content in milk and CH4 production and cis-9 14:1 and CH4 production (r = -0.47). Myristic acid had no effect on the contents of CLA or trans-10 18:1 and trans-11 18:1 isomers in milk. These results suggest that MA could be used to inhibit the activities of methanogens in ruminant animals without altering the conjugated linoleic acid and trans-18:1 fatty acid profile in milk.


Subject(s)
Cattle/physiology , Dietary Supplements , Methane/biosynthesis , Milk , Myristic Acid/administration & dosage , Rumen/drug effects , Animal Feed/analysis , Animals , Dairying , Eating/physiology , Fatty Acids/chemistry , Fatty Acids/metabolism , Female , Lactation/drug effects , Lactation/physiology , Milk/chemistry , Milk/drug effects , Milk Proteins/analysis , Rumen/metabolism
16.
Food Chem Toxicol ; 45(4): 517-29, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17141389

ABSTRACT

Myristic acid is used in the food industry as a flavor ingredient. It is found widely distributed in fats throughout the plant and animal kingdom, including common human foodstuffs, such as nutmeg. Myristic acid (a 14-carbon, straight-chain saturated fatty acid) has been shown to have a low order of acute oral toxicity in rodents. It may be irritating in pure form to skin and eyes under exaggerated exposure conditions, but is not known or predicted to induce sensitization responses. Myristic acid did not induce a mutagenic response in either bacterial or mammalian systems in vitro. Relevant subchronic toxicity data are available on closely related fatty acid analogs. In particular, a NOEL of >6000mg/kg was reported for lauric acid (a 12-carbon, straight-chain saturated fatty acid) following dietary exposure to male rats for 18 weeks and a NOEL of >5000mg/kg was reported for palmitic acid (a 16-carbon, straight-chain saturated fatty acid) following dietary exposure to rats for 150 days. The data and information that are available indicate that at the current level of intake, food flavoring use of myristic acid does not pose a health risk to humans.


Subject(s)
Flavoring Agents/toxicity , Myristic Acid/toxicity , Absorption , Animals , Humans , Myristic Acid/administration & dosage , Myristic Acid/pharmacokinetics , Risk Assessment , Safety
17.
Br J Nutr ; 96(2): 283-9, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16923222

ABSTRACT

The present study evaluated the effects of moderate intakes of myristic acid (MA), at 1.2% and 1.8% of total energy (TE), associated with a 0.9% TE intake of alpha-linolenic acid (ALA) on lipid and fatty acid profiles and red blood cell membrane fluidity. Twenty-nine monks without dyslipidaemia were enrolled in a 1-year nutritional study in which two experimental diets were tested for 3 months each: diet 1, MA 1.2 % and ALA 0.9%; diet 2, MA 1.8% and ALA 0.9%. A control diet (MA 1.2%, ALA 0.4%) was given 3 months before diets 1 and 2. Thus, two different levels of MA (1.2%, 1.8%) and ALA (0.4%, 0.9%) were tested. Intakes of other fatty acids were at recommended levels. Samples were obtained on completion of all three diets. For fluidity analysis, the red blood cells were labelled with 16-doxylstearate and the probe incorporated the membrane where relaxation-correlation time was calculated. Diet 1 was associated with a decrease in total cholesterol, in LDL-cholesterol, in triacylglycerols and in the ratio of total to HDL-cholesterol; ALA and EPA levels were increased in both phospholipids and cholesterol esters. Diet 2 was associated with a decrease in triacylglycerols and in the ratios of total to HDL-cholesterol and of triacylglycerols to HDL-cholesterol, and with an increase in HDL-cholesterol; EPA levels were decreased in phospholipids and cholesterol esters. Red blood cell membrane fluidity was increased in both diets (P<0.0001), but the higher increase was obtained with diet 1, mainly in the oldest subjects. Intakes of myristic acid (1.2%TE) and ALA (0.9%TE), both mainly in the sn-2 position, were associated with favourable lipid and n-3 long-chain fatty acid profiles. These beneficial effects coexisted with particularly high membrane fluidity, especially among the oldest subjects.


Subject(s)
Erythrocytes/drug effects , Lipids/blood , Membrane Fluidity/drug effects , Myristic Acid/pharmacology , alpha-Linolenic Acid/pharmacology , Adult , Aged , Aged, 80 and over , Anthropometry , Apoproteins/blood , Cholesterol Esters/blood , Diet , Erythrocytes/physiology , Humans , Lipoproteins/blood , Male , Middle Aged , Myristic Acid/administration & dosage , Nutritional Physiological Phenomena , Phospholipids/blood , alpha-Linolenic Acid/administration & dosage
18.
Pharmazie ; 60(11): 840-3, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16320946

ABSTRACT

Liposomes accumulating in the reticuloendothelial system (RES) appear to be a promising vehicle to improve the therapeutic index of anti-HIV drugs such as zidovudine (AZT). Since the entrapment efficiency of AZT in liposomes was found to be low and AZT leakage from liposomes is fast, zidovudine myristate (AZT-M) was synthesized as a prodrug, and AZT-M incorporated liposomes in a lyophilized form were prepared with an average diameter of 90 nm and an encapsulation efficiency of 98% after reconstitution. The pharmacokinetic profiles and tissue distribution of AZT after i.v. administration of AZT-M liposomes in rats were investigated, and the results were compared with those after i.v. administration of AZT solution. AZT levels in plasma were significantly higher following application of AZT-M liposomes compared with AZT solution, and AUC0_infinity increased from 5.0 +/- 0.7 micromol x min x ml(-1) to 8.2 +/- 1.7 micromol x min x ml(-1) accordingly. Tissue distribution studies also confirmed higher concentrations of AZT in organs of RES and brain, suggesting that AZT-M liposomes might be promising candidates for therapy of HIV infections.


Subject(s)
Anti-HIV Agents/pharmacokinetics , Myristic Acid/pharmacokinetics , Zidovudine/pharmacokinetics , Animals , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/chemical synthesis , Disaccharides , Drug Carriers , Female , Half-Life , Injections, Intravenous , Liposomes , Magnetic Resonance Spectroscopy , Male , Myristic Acid/administration & dosage , Myristic Acid/chemical synthesis , Particle Size , Rats , Rats, Wistar , Spectrophotometry, Infrared , Suspensions , Tissue Distribution , Zidovudine/administration & dosage , Zidovudine/chemical synthesis
19.
Reprod Nutr Dev ; 45(5): 599-612, 2005.
Article in English | MEDLINE | ID: mdl-16188210

ABSTRACT

This study was designed to investigate the effect of myristic acid on the biosynthesis and metabolism of highly unsaturated fatty acids, when it is supplied in a narrow physiological range in the diet of the rat (0.2-1.2% of total dietary energy). Three experimental diets were designed, containing 22% of total dietary energy as lipids and increasing doses of myristic acid (0.71, 3.00 and 5.57% of total fatty acids). Saturated fat did not exceed 31% of total fat and the C18:3 n-3 amount in each diet was strictly equal (1.6% of total fatty acids). After 7 weeks, the diets had no effect on plasma cholesterol level but greatly modified the liver, plasma and adipose tissue saturated, monounsaturated and polyunsaturated fatty acid profiles. Firstly, daily intakes of myristic acid resulted in a dose-dependent tissue accumulation of myristic acid itself. Palmitic acid was significantly increased in the tissues of the rats fed the higher dose of myristic acid. A dose-response accumulation of tissue C16:1 n-7 as a function of dietary C14:0 was also shown. Secondly, a main finding was that, among n-3 and n-6 polyunsaturated fatty acids, a dose-response accumulation of liver and plasma C20:5 n-3 and C20:3 n-6 (two precursors of eicosanoids) as a function of dietary C14:0 was shown. This result suggests that dietary myristic acid may participate in the regulation of highly unsaturated fatty acid biosynthesis and metabolism.


Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/metabolism , Liver/metabolism , Myristic Acid/metabolism , Adipose Tissue/metabolism , Animals , Dietary Fats, Unsaturated/blood , Dietary Fats, Unsaturated/metabolism , Dose-Response Relationship, Drug , Fatty Acid Desaturases/metabolism , Fatty Acids, Unsaturated/biosynthesis , Fatty Acids, Unsaturated/blood , Male , Myristic Acid/administration & dosage , Myristic Acid/blood , Organ Size , Random Allocation , Rats , Rats, Sprague-Dawley
20.
J Nutr Biochem ; 16(6): 375-82, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15936650

ABSTRACT

Among the saturated fatty acids (SFA), myristic acid is known to be one of the most atherogenic when consumed at high levels. Our purpose was to compare the effects of two moderate intakes of myristic acid on plasma lipids in an interventional study. Twenty-five male monks without dyslipidemia were given two isocaloric diets for 5 weeks each. In diet 1, 30% of the calories came from fat (8% SFA, 0.6% myristic acid) and provided 200 mg cholesterol/day. Calories of diet 2 were 34% fat (11% SFA, 1.2% myristic acid) with the same levels of oleate, linoleate, alpha-linolenate and cholesterol. A baseline diet was provided before each diet. In comparison with baseline, diets 1 and 2 induced a decrease in total cholesterol, LDL-cholesterol and triglycerides (P<.001); HDL-cholesterol was not modified and the apo A-I/apo B ratio increased (P<.001). Plasma triglycerides were lower after diet 2 than after diet 1 whereas HDL-cholesterol was higher (P<.05). In phospholipids, myristic acid, oleic acid, linoleic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increased after diet 2 vs. baseline (P<.01) and diet 1 (P<.05). Both diets were associated with an increase in alpha-linolenate of cholesteryl esters (P<.05), but only diet 2 was associated with an increase in DHA of cholesteryl esters (P<.05). In diet 2, myristic acid intake was positively correlated with myristic acid of phospholipids, and alpha-linolenic acid intake was correlated with alpha-linolenic acid of cholesteryl esters. Moderate intake (1.2% of total calories) of myristic acid has beneficial lipidic effects and enhances DHA of cholesteryl esters.


Subject(s)
Dietary Fats/administration & dosage , Dietary Fats/pharmacology , Docosahexaenoic Acids/blood , Lipids/blood , Myristic Acid/administration & dosage , Myristic Acid/pharmacology , Adult , Aged , Aged, 80 and over , Cholesterol Esters/blood , Fatty Acids/blood , Humans , Male , Middle Aged , Myristic Acid/chemistry , Phospholipids/blood
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