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Molecules (Basel, Switzerland) Nov 2023To disperse fatty acids in aqueous solution, choline, a quaternary ammonium ion, has been used recently. So far, only the self-assembly of myristic acid (MA) in the...
To disperse fatty acids in aqueous solution, choline, a quaternary ammonium ion, has been used recently. So far, only the self-assembly of myristic acid (MA) in the presence of choline hydroxide as a function of the molar ratio has been investigated, and, thus, the current understanding of these fatty acid systems is still limited. We investigated the self-assembly of palmitic acid (PA) in the presence of choline hydroxide (ChOH) as a function of the molar ratio () between ChOH and PA. The self-assemblies were characterized by phase contrast microscopy, cryo-TEM, small-angle X-ray scattering, and H NMR. The ionization state of PA was determined by pH, conductivity, and FT-IR measurements. With increase in , various self-assembled structures, including vesicles, lamellar phase, rigid membranes (large sheets, tubules, cones, and polyhedrals), and micelles, form in the PA/ChOH system, different from those of the MA/ChOH system. The change in induces pH variation and, consequently, a change in the PA ionization state, which, in turn, regulates the molecular interactions, including hydrogen bonding and electrostatic interaction, leading to various self-assemblies. Temperature is an important factor used to tune the self-assembly transitions. The fatty acid choline systems studied here potentially may be applicable in medicine, chemical engineering, and biotechnology.
PubMed: 38005186
DOI: 10.3390/molecules28227463 -
The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids.The EMBO Journal Feb 2024The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal...
The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory models prior to the development of neuromuscular deficits that mirror human spastic paraplegia. Via pulldown-mass spectrometry analyses, we find that DDHD2 binds to the key synaptic protein STXBP1. Using STXBP1/2 knockout neurosecretory cells and a haploinsufficient STXBP1 mouse model of human early infantile encephalopathy associated with intellectual disability and motor dysfunction, we show that STXBP1 controls targeting of DDHD2 to the plasma membrane and generation of saturated FFAs in the brain. These findings suggest key roles for DDHD2 and STXBP1 in lipid metabolism and in the processes of synaptic plasticity, learning, and memory.
Topics: Animals; Mice; Brain; Fatty Acids, Nonesterified; Memory; Memory, Long-Term; Munc18 Proteins; Phospholipases
PubMed: 38316990
DOI: 10.1038/s44318-024-00030-7 -
Journal of Clinical Lipidology 2023The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake.
BACKGROUND
The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake.
PURPOSE
To evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters.
METHODS
In a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements.
RESULTS
Main differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001).
CONCLUSIONS
This study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.
Topics: Humans; Fatty Acids; Cholesterol Esters; Dietary Fats; Fatty Acids, Monounsaturated; Diet; Fish Oils
PubMed: 37263854
DOI: 10.1016/j.jacl.2023.05.095 -
Heliyon Mar 2024Previous studies offer inconclusive results on the association between diet-derived circulating antioxidants and epilepsy.
BACKGROUND
Previous studies offer inconclusive results on the association between diet-derived circulating antioxidants and epilepsy.
OBJECTIVE
This study aims to assess oxidative stress presence in epilepsy patients' circulation and investigate the causal link between diet-derived circulating antioxidants and epilepsy.
METHODS
Untargeted metabolomics analysis was conducted on plasma samples from 62 epileptic patients and 20 healthy individuals to evaluate oxidative stress based on metabolite alterations in epilepsy patients' circulation. Two-sample Mendelian Randomization (MR) analysis examined the causation between diet-derived circulating antioxidants (measured by absolute levels and relative metabolite concentrations) and epilepsy, utilizing the inverse-variance weighted (IVW) method as the primary outcome, with complementary MR analysis methods (MR Egger, weighted median, weighted mode, and simple mode).
RESULTS
Untargeted metabolomics analysis revealed elevated circulating oxidizing metabolites (palmitic acid, oleic acid, linoleic acid, and myristic acid) and reduced reducing metabolites (glutamine) in epilepsy patients, providing robust evidence of oxidative stress. The IVW analysis indicated significantly reduced epilepsy risk (odds ratio: 0.552; 95% confidence interval: 0.335-0.905, = 0.018) with genetically determined higher absolute circulating β-carotene. However, other diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, and selenium) and antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbic acid, and retinol) did not significantly associate with epilepsy risk. Additional MR analysis methods and heterogeneity assessments confirmed the results' robustness.
CONCLUSION
This study provides compelling evidence of oxidative stress in epilepsy patients' circulation. However, the majority of diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, vitamin E, and selenium) are unlikely to causally associate with reduced epilepsy risk, except for β-carotene.
PubMed: 38463786
DOI: 10.1016/j.heliyon.2024.e26813 -
Food Chemistry. Molecular Sciences Jul 2024Sugar and fatty acid content are among the important factors that contribute to the intensity of flavor in aromatic coconut. Gaining a comprehensive understanding of the...
Sugar and fatty acid content are among the important factors that contribute to the intensity of flavor in aromatic coconut. Gaining a comprehensive understanding of the sugar and fatty acid metabolites in the flesh of aromatic coconuts, along with identifying the key synthetic genes, is of significant importance for improving the development of desirable character traits in these coconuts. However, the related conjoint analysis of metabolic targets and molecular synthesis mechanisms has not been carried out in aromatic coconut until now. UPLC-MS/MS combined with RNA-Seq were performed in aromatic coconut (AC) and non-aromatic coconut (NAC) meat at 7, 9 and 11 months. The results showed that D-fructose in AC coconut meat was 3.48, 2.56 and 3.45 fold higher than that in NAC coconut meat. Similarly, D-glucose in AC coconut meat was 2.48, 2.25 and 3.91 fold higher than that in NAC coconut meat. The NAC coconut meat showed a 1.22-fold rise in the content of lauric acid compared to the AC coconut meat when it reached 11 months of age. Myristic acid content in NAC coconut meat was 1.47, 1.44 and 1.13 fold higher than that in AC coconut meat. The palmitic acid content in NAC coconut meat was 1.62 and 1.34 fold higher than that in AC coconut meat. The genes , , , , , , , , , , , , , , , exhibited a negative correlation with D-fructose (r = -0.81) and D-glucose (r = -0.99) contents, while showing a positive correlation (r = 0.85-0.96) with lauric acid and myristic acid. Furthermore, , , , , and displayed a positive correlation (r = 0.83-0.94) with palmitic acid content. The sugar/organic acid ratio exhibited a positive correlation with , , , , and .
PubMed: 38259870
DOI: 10.1016/j.fochms.2023.100190 -
International Journal of Nanomedicine 2023Quetiapine (QTP) is a first-line antipsychotic drug, but its therapeutic druggability and patient adherence were limited due to high oral dose strength, low...
BACKGROUND
Quetiapine (QTP) is a first-line antipsychotic drug, but its therapeutic druggability and patient adherence were limited due to high oral dose strength, low bioavailability and physicochemical/biopharmaceutical issues.
PURPOSE
To investigate the roles of fatty acid chain length and enzyme-oriented QTP controlled release from pH-triggering self-assembled fatty acid conjugated QTP nanosuspensions (NSPs).
METHODS
QTP was conjugated with different chain length fatty acids (C10-decanoic acid, C14-myristic acid, C18-stearic acid) to obtain QTP-fatty acid conjugates (QFCs: QD, QM, QS) by exploiting 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/4-dimethylaminopyridine (EDC/DMAP) conjugation chemistry. Then, the solubility, partitioning coefficient (log P), cell viability and cleavage kinetics of QFCs were evaluated. The pH-triggering self-assembled behaviors of QFCs to form QTP-fatty acid NSPs (QDN, QMN, QSN) by varying pH, QFC concentration and proton-to-QTP ratios were characterized. The morphological images, critical micelle concentration (CMC), physicochemical properties and enzyme-oriented QTP controlled release of NSPs were examined.
RESULTS
Three QFCs were synthesized with different chain length fatty acids from QTP after desalting fumarate from QTP fumarate. The pH, QFC concentration and proton-to-quetiapine molar ratio could influence physicochemical properties and nanonization behaviors of QFCs. All three QFCs showed no effect on the viability of myoblast cells. The pH-triggering self-assembly of amphiphilic QFCs to form nanoparticles (NPs) occurred as the amine moiety of QTP was readily ionized in a strongly acidic environment (pH 1.2). Interestingly, the longer the fatty acid chain length, the lower water solubility, the higher log P (lipophilicity) and the smaller NP particle size were observed. The conversion rate of QFCs to liberate QTP by esterase in human plasma and liver S9 fractions was also inversely proportional to the fatty acid carbon chain length. Interestingly, the freeze-dried QMN showed the esterase-oriented controlled release of QTP over one month, unlike the initial burst release of QDN or the slowly delayed release pattern of QSN.
CONCLUSION
A new pH-triggering self-assembled nanonization platform was developed using different chain length fatty acid conjugated QTP in low pH environment. By varying fatty acid chain length, the enzyme-oriented QTP controlled release dosage form was challenged to enhance the therapeutic effectiveness of QTP.
Topics: Humans; Quetiapine Fumarate; Fatty Acids; Delayed-Action Preparations; Protons; Hydrogen-Ion Concentration; Esterases; Fumarates
PubMed: 38054081
DOI: 10.2147/IJN.S440207 -
Journal of Materials Chemistry. B Nov 2023Emulsion-templated foams have displayed promise as injectable bone grafts; however, the use of a surfactant as an emulsifier resulted in relatively small pores and...
Emulsion-templated foams have displayed promise as injectable bone grafts; however, the use of a surfactant as an emulsifier resulted in relatively small pores and impedes cell attachment. Hydroxyapatite nanoparticles were explored as an alternative stabilizer to address these limitations. To this end, hydroxyapatite nanoparticles were first modified with myristic acid to generate the appropriate balance of hydrophobicity to stabilize a water-in-oil emulsion of neopentyl glycol diacrylate and 1,4-butanedithiol. surface modification of the resulting foam with hydroxyapatite was confirmed with elemental mapping and transmission electron microscopy. Nanoparticle-stabilized foams displayed improved human mesenchymal stem cell viability (91 ± 5%) over surfactant-stabilized foams (23 ± 11%). Although the pore size was appropriate for bone grafting applications (115 ± 71 μm), the foams lacked the interconnected architecture necessary for cell infiltration. We hypothesized that a co-stabilization approach with both surfactant and nanoparticles could be used to achieve interconnected pores while maintaining improved cell attachment and larger pore sizes. A range of hydroxyapatite nanoparticle and surfactant concentrations were investigated to determine the effects on microarchitecture and cell behavior. By balancing these interactions, a co-stabilized foam was identified that possessed large, interconnected pores (108 ± 67 μm) and improved cell viability and attachment. The co-stabilized foam was then evaluated as an injectable bone graft including network formation, microscale integration with bone, push out strength, and compressive properties. Overall, this work demonstrated that surface modification with nHA improved cell attachment while retaining desirable bone grafting features and injectability.
Topics: Humans; Porosity; Bone Transplantation; Emulsions; Durapatite; Nanoparticles; Surface-Active Agents
PubMed: 37878081
DOI: 10.1039/d3tb01839c -
Molecules (Basel, Switzerland) Nov 2023Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang...
Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang Dynasty. (HK) is the most common seahorse species in the medicinal material market and is one of the genuine sources of medicinal seahorse documented in the Chinese pharmacopeia. It is mainly cultivated in the Shandong, Fujian, and Guangxi Provinces in China. However, pseudo-HK, represented by (HI) due to its similar appearance and traits, is often found in the market, compromising the safety and efficacy of clinical use. Currently, there is a lack of reliable methods for identifying these species based on their chemical composition. In this study, we employed, for the first time, a strategy combining gas chromatography-mass spectrometry (GC-MS) fingerprints and chemical patterns in order to identify HK and HI; it is also the first metabolomic study to date of HI as to chemical components. The obtained results revealed remarkable similarities in the chemical fingerprints, while significant differences were also observed. By employing hierarchical cluster analysis (HCA) and principal component analysis (PCA), based on the relative contents of their characteristic peaks, all 34 samples were successfully differentiated according to their species of origin, with samples from the same species forming distinct clusters. Moreover, nonadecanoic acid and behenic acid were exclusively detected in HK samples, further distinguishing them from HI samples. Additionally, the relative contents of lauric acid, tetradecanoic acid, pentadecanoic acid, n-hexadecanoic acid, palmitoleic acid, margaric acid, oleic acid, fenozan acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) exhibited significant differences between HK and HI ( < 0.0001), as determined by an unpaired -test. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified seven components (DHA, EPA, n-hexadecanoic acid, tetradecanoic acid, palmitoleic acid, octadecanoic acid, and margaric acid) with high discriminatory value (VIP value > 1). Thus, nonadecanoic acid, behenic acid, and these seven compounds can be utilized as chemical markers for distinguishing HK from HI. In conclusion, our study successfully developed a combined strategy of GC-MS fingerprinting and chemical pattern recognition for the identification of HK and HI, and we also discovered chemical markers that can directly differentiate between the two species. This study can provide a foundation for the authentication of Hippocampus and holds significant importance for the conservation of wild seahorse resources.
Topics: Animals; Gas Chromatography-Mass Spectrometry; Myristic Acid; Smegmamorpha; China; Cluster Analysis; Chromatography, High Pressure Liquid; Principal Component Analysis
PubMed: 38067553
DOI: 10.3390/molecules28237824 -
Microorganisms Oct 2023In this research, six strains of oleaginous yeasts native to southern Chile were analyzed for their biotechnological potential in lipid accumulation. For this purpose,...
In this research, six strains of oleaginous yeasts native to southern Chile were analyzed for their biotechnological potential in lipid accumulation. For this purpose, the six strains, named PP1, PP4, PR4, PR10, PR27 and PR29, were cultivated in a nitrogen-deficient synthetic mineral medium (SMM). Then, two strains were selected and cultivated in an industrial residual "vinasse", under different conditions of temperature (°C), pH and carbon/nitrogen (C/N) ratio. Finally, under optimized conditions, the growth kinetics and determination of the lipid profile were evaluated. The results of growth in the SMM indicate that yeasts PP1 and PR27 presented biomass concentrations and lipid accumulation percentages of 2.73 and 4.3 g/L of biomass and 36.6% and 45.3% lipids, respectively. Subsequently, for both strains, when cultured in the residual vinasse under optimized environmental conditions, biomass concentrations of 14.8 ± 1.51 g/L (C/N 80) and 15.83 ± 0.57 g/L (C/N 50) and lipid accumulations of 28% and 30% were obtained for PP1 and PR27, respectively. The composition of the triglycerides (TGs), obtained in the culture of the yeasts in a 2 L reactor, presented 64.25% of saturated fatty acids for strain PR27 and 47.18% for strain PP1. The saturated fatty acid compositions in both strains are mainly constituted of fatty acids, myristic C 14:0, heptadecanoic C 17:0, palmitic C 16:0 and stearic C 18:0, and the monounsaturated fatty acids constituted of oleic acid C 18:1 (cis 9) (28-46%), and in smaller amounts, palmitoleic acid and heptadecenoic acid. This work demonstrates that the native yeast strains PP1 and PR27 are promising strains for the production of microbial oils similar to conventional vegetable oils. The potential applications in the energy or food industries, such as aquaculture, are conceivable.
PubMed: 37894174
DOI: 10.3390/microorganisms11102516 -
Frontiers in Endocrinology 2023N-lactoylphenylalanine (Lac-Phe) is a new form of "exerkines" closely related to lactate (La), which may be able to inhibit appetite. Blood flow restriction (BFR) can... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
N-lactoylphenylalanine (Lac-Phe) is a new form of "exerkines" closely related to lactate (La), which may be able to inhibit appetite. Blood flow restriction (BFR) can lead to local tissue hypoxia and increase lactate accumulation. Therefore, this study investigated the effects of combining Moderate-intensity Continuous Exercise (MICE) with BFR on Lac-Phe and appetite regulation in obese adults.
METHODS
This study employed the cross-design study and recruited 14 obese adults aged 18-24 years. The participants were randomly divided into three groups and performed several tests with specific experimental conditions: (1) M group (MICE without BFR, 60%VO, 200 kJ); (2) B group (MICE with BFR, 60%VO, 200 kJ); and (3) C group (control session without exercise). Participants were given a standardized meal 60 min before exercise and a ad libitum 60 min after exercise. In addition, blood and Visual Analogue Scale (VAS) were collected before, immediately after, and 1 hour after performing the exercise.
RESULTS
No significant difference in each index was detected before exercise. After exercise, the primary differential metabolites detected in the M and B groups were xanthine, La, succinate, Lac-Phe, citrate, urocanic acid, and myristic acid. Apart from that, the major enrichment pathways include the citrate cycle, alanine, aspartate, and glutamate metabolism. The enhanced Lac-Phe and La level in the B group was higher than M and C groups. Hunger of the B group immediately after exercise substantially differed from M group. The total ghrelin, glucagon-like peptide-1 and hunger in the B group 1 hour after exercise differed substantially from M group. The results of calorie intake showed no significant difference among the indexes in each group.
CONCLUSIONS
In conclusion, this cross-design study demonstrated that the combined MICE and BFR exercise reduced the appetite of obese adults by promoting the secretion of Lac-Phe and ghrelin. However, the exercise did not considerably affect the subsequent ad libitum intake.
Topics: Adult; Humans; Appetite Regulation; Blood Flow Restriction Therapy; Citrates; Ghrelin; Lactates; Obesity
PubMed: 38116312
DOI: 10.3389/fendo.2023.1289574