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The Journal of Physiology Sep 2023Well-regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with...
Well-regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo-inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope-labelled C-PA or C-OA for 48 h. Explants were treated with glucose (5, 10 mm) or leptin (13 nm) or insulin (150 nm) in combination with myo-inositol (0.3, 30, 60 μm). Forty-seven C-PA lipids and 37 C-OA lipids were measured by liquid chromatography-mass spectrometry (LCMS). Compared with controls (5 mm glucose), glucose (10 mm) increased 19 C-OA lipids and nine C-PA lipids, but decreased C-OA phosphatidylethanolamine 38:5 and C-PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing C-OA acylcarnitine 18:1, and insulin increasing four C-PA triacylglycerides. Most glucose, leptin and insulin-induced alterations in lipids were attenuated by co-incubation with myo-inositol (30 or 60 μm), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose-induced increases in acylcarnitine were not attenuated by myo-inositol and were even exaggerated in some instances. Myo-inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta in vitro. Whether myo-inositol protects the fetus and pregnancy from unfavourable outcomes requires further research. KEY POINTS: Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of C-lipids from C-palmitic acid (PA) and C-oleic acid (OA) in vitro compared with untreated controls from the same placenta. Co-incubation with myo-inositol attenuated most alterations induced by glucose, insulin or leptin in C-lipids, but did not affect alterations in C-acylcarnitines. Alterations induced by glucose and leptin in C-PA triacylglycerides and C-PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo-inositol co-incubation. Insulin differently affected C-PA triacylglycerides and C-PA phospholipids depending on fetal sex, with alterations also attenuated by myo-inositol co-incubation.
Topics: Pregnancy; Female; Humans; Insulin; Oleic Acid; Palmitic Acid; Phosphatidylethanolamines; Leptin; Diabetes, Gestational; Placenta; Glucose
PubMed: 37602663
DOI: 10.1113/JP285036 -
Accounts of Chemical Research Oct 2023ConspectusAerosols are ubiquitous in the atmosphere. Outdoors, they take part in the climate system via cloud droplet formation, and they contribute to indoor and...
ConspectusAerosols are ubiquitous in the atmosphere. Outdoors, they take part in the climate system via cloud droplet formation, and they contribute to indoor and outdoor air pollution, impacting human health and man-made environmental change. In the indoor environment, aerosols are formed by common activities such as cooking and cleaning. People can spend up to . 90% of their time indoors, especially in the western world. Therefore, there is a need to understand how indoor aerosols are processed in addition to outdoor aerosols.Surfactants make significant contributions to aerosol emissions, with sources ranging from cooking to sea spray. These molecules alter the cloud droplet formation potential by changing the surface tension of aqueous droplets and thus increasing their ability to grow. They can also coat solid surfaces such as windows ("window grime") and dust particles. Such surface films are more important indoors due to the higher surface-to-volume ratio compared to the outdoor environment, increasing the likelihood of surface film-pollutant interactions.A common cooking and marine emission, oleic acid, is known to self-organize into a range of 3-D nanostructures. These nanostructures are highly viscous and as such can impact the kinetics of aerosol and film aging (i.e., water uptake and oxidation). There is still a discrepancy between the longer atmospheric lifetime of oleic acid compared with laboratory experiment-based predictions.We have created a body of experimental and modeling work focusing on the novel proposition of surfactant self-organization in the atmosphere. Self-organized proxies were studied as nanometer-to-micrometer films, levitated droplets, and bulk mixtures. This access to a wide range of geometries and scales has resulted in the following main conclusions: (i) an atmospherically abundant surfactant can self-organize into a range of viscous nanostructures in the presence of other compounds commonly encountered in atmospheric aerosols; (ii) surfactant self-organization significantly reduces the reactivity of the organic phase, increasing the chemical lifetime of these surfactant molecules and other particle constituents; (iii) while self-assembly was found over a wide range of conditions and compositions, the specific, observed nanostructure is highly sensitive to mixture composition; and (iv) a "crust" of product material forms on the surface of reacting particles and films, limiting the diffusion of reactive gases to the particle or film bulk and subsequent reactivity. These findings suggest that hazardous, reactive materials may be protected in aerosol matrixes underneath a highly viscous shell, thus extending the atmospheric residence times of otherwise short-lived species.
PubMed: 37688543
DOI: 10.1021/acs.accounts.3c00194 -
BioRxiv : the Preprint Server For... Dec 2023Bacterial vaginosis (BV), a common syndrome characterized by -deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard...
Bacterial vaginosis (BV), a common syndrome characterized by -deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by instead of , which has more beneficial health associations. Strategies to promote and inhibit are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit and enhance growth. These phenotypes require OA-inducible genes conserved in and related species, including an oleate hydratase () and putative fatty acid efflux pump (). FarE mediates OA resistance, while OhyA is robustly active in the human vaginal microbiota and sequesters OA in a derivative form that only -harboring organisms can exploit. Finally, OA promotes dominance more effectively than antibiotics in an model of BV, suggesting a novel approach for treatment.
PubMed: 38234804
DOI: 10.1101/2023.12.30.573720 -
Molecules (Basel, Switzerland) Oct 2023Hepatic steatosis can cause liver dysfunction and cell injury, on which natural functional factors are expected to be an effective approach for long-term intervention....
Hepatic steatosis can cause liver dysfunction and cell injury, on which natural functional factors are expected to be an effective approach for long-term intervention. However, the cellular molecular mechanisms are unclear. Chlorogenic acid is a phenolic compound, which can regulate lipid metabolism and is abundant in burdock root. The aim of this study was to investigate the potential molecular mechanism of the effect of chlorogenic acid from burdock root (ACQA) on steatosis in HepG2 cells. In this study, we found that ACQA reduced the number of lipid droplets and lipid levels in oleic acid-treated HepG2 cells. Molecular mechanistic results showed that ACQA enhanced CPT-1 expression by activating AMPK-related signaling pathways, and the concentrations of Ca and cAMP were increased with the intervention of ACQA. In addition, ACQA enhanced the β-oxidation of fatty acids, reduced alanine transaminase and aspartate transaminase, and inhibited apoptosis in oleic acid-treated HepG2 cells. Our studies elucidate a novel mechanism that ACQA enhances the β-oxidation of fatty acids through the AMPK/ACC/CPT-1 pathway to protect against steatosis in HepG2 cells, which provides insight into its molecular mechanism as well as intervention strategies for chlorogenic acid against fatty liver diseases.
Topics: Humans; Hep G2 Cells; AMP-Activated Protein Kinases; Chlorogenic Acid; Arctium; Oleic Acid; Non-alcoholic Fatty Liver Disease; Lipid Metabolism; Fatty Acids; Liver
PubMed: 37959676
DOI: 10.3390/molecules28217257 -
ACS Omega Feb 2024A novel combination of antibiotic, ciprofloxacin (CIP) with herbal counterpart naringin (NAR) was encapsulated by an oleic acid lipid core and carboxymethyl chitosan...
Co-Delivery of Naringin and Ciprofloxacin by Oleic Acid Lipid Core Encapsulated in Carboxymethyl Chitosan/Alginate Nanoparticle Composite for Enhanced Antimicrobial Activity.
A novel combination of antibiotic, ciprofloxacin (CIP) with herbal counterpart naringin (NAR) was encapsulated by an oleic acid lipid core and carboxymethyl chitosan (CM-CS)/Alginate (AG) nanoparticle composite (CIP + NAR-CM-CS/AG-NPs) for improved antimicrobial efficacy of antibiotic. Herein, this study explored the design and preparation of a composite system that enables to deliver both CIP and NAR from the oleic acid lipid core of CM-CS/AG nanoparticles using a nonsolvent ionic gelation technique. The nanoparticles (NPs) were fabricated with improved long-acting antimicrobial activity against and . The optimized composition was investigated for physicochemical properties particle size, particle distribution, and ζ-potential. A diverse array of analytical tools was employed to characterize the optimized formulation including DSC, XRD, Malvern Zetasizer for particle size, ζ-potential, TEM, and SEM. Further, the preparation was investigated for % drug release, flux determination, antioxidant, and antimicrobial activity. The formulation stability was tested for 90 days and also evaluated formulation stability in fetal bovine serum to inspect the modification in physicochemical characteristics. NPs size was determined at 85 nm, PDI, and ζ-potential was recorded at 0.318, and 0.7 ± 0.4 mV. The % CIP and NAR entrapment efficiency and % loading were incurred as 91 ± 1.9, and 89.5 ± 1.2; 11.5 ± 0.6, and 10.8 ± 0.5%, respectively. The drug release erupted in the beginning phase followed by sustained and prolonged release for 48 h. The analytical experiments by DSC ensured the noninteracting and safe use of excipients in combination. X-ray studies demonstrated the amorphous state of the drug in the formulation. The insignificant alteration of formulation characteristics in FBS suggested stable and robust preparation. Storage stability of the developed formulation ensured consistent and uniform stability for three months. The DPPH assays demonstrated that NAR had good antioxidant capacity and supported improving antimicrobial activity of CIP. The hemolytic test suggested the developed formulation was compatible and caused insignificant RBC destruction. The in-house built formulation CIP + NAR-CM-CS/AG-NPs significantly improved the antimicrobial activity compared to CIP alone, offering a novel choice in antimicrobial application.
PubMed: 38371782
DOI: 10.1021/acsomega.3c08200 -
Polymers Dec 2023Unsaturated fatty acids, such as oleic acid (OA) and linoleic acid (LA), are promising antimicrobial and cytostatic agents. We modified OA and LA with thymol (TOA and...
Unsaturated fatty acids, such as oleic acid (OA) and linoleic acid (LA), are promising antimicrobial and cytostatic agents. We modified OA and LA with thymol (TOA and TLA, respectively) to expand their bioavailability, stability, and possible applications, and encapsulated these derivatives in polymeric nanoparticles (TOA-NPs and TLA-NPs, respectively). Prior to synthesis, we performed mathematical simulations with PASS and ADMETlab 2.0 to predict the biological activity and pharmacokinetics of TOA and TLA. TOA and TLA were synthesized via esterification in the presence of catalysts. Next, we formulated nanoparticles using the single-emulsion solvent evaporation technique. We applied dynamic light scattering, Uv-vis spectroscopy, release studies under gastrointestinal (pH 1.2-6.8) and blood environment simulation conditions (pH 7.4), and in vitro biological activity testing to characterize the nanoparticles. PASS revealed that TOA and TLA have antimicrobial and anticancer therapeutic potential. ADMETlab 2.0 provided a rationale for TOA and TLA encapsulation. The nanoparticles had an average size of 212-227 nm, with a high encapsulation efficiency (71-93%), and released TOA and TLA in a gradual and prolonged mode. TLA-NPs possessed higher antibacterial activity against and and pronounced cytotoxic activity against MCF-7, K562, and A549 cell lines compared to TOA-NPs. Our findings expand the biomedical application of fatty acids and provide a basis for further in vivo evaluation of designed derivatives and formulations.
PubMed: 38201737
DOI: 10.3390/polym16010072 -
Alzheimer's & Dementia : the Journal of... May 2024Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear.
INTRODUCTION
Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear.
METHODS
The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC-FID. The MCI subjects were followed up for 58 ± 12.5 months.
RESULTS
In controls, CSF has a more neuroprotective LFA than plasma. In CSF, a higher content of docosahexaenoic acid was associated with a reduced risk of MCI-to-AD progression. In plasma, higher oleic acid content was associated with lower risk of AD, MCI, and MCI-to-AD progression, whereas higher levels of vaccenic acid and docosahexaenoic acid were associated with greater risk of AD and MCI, and higher rate of MCI-to-AD progression, respectively.
DISCUSSION
The circulating LFA is involved in the pathogenesis and progression of AD.
HIGHLIGHTS
The lipidome fatty acid profile in CSF and plasma was markedly different. Higher levels of vaccenic acid and lower levels of oleic acid in plasma were associated with greater risk of Alzheimer's disease. In plasma, higher levels of oleic acid were associated with a reduced risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in CSF were associated with a lower risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in plasma were associated with a greater rate of MCI-to-AD progression.
Topics: Humans; Alzheimer Disease; Male; Female; Fatty Acids; Aged; Lipidomics; Disease Progression; Cognitive Dysfunction; Biomarkers; Docosahexaenoic Acids; Middle Aged
PubMed: 38534027
DOI: 10.1002/alz.13792 -
Cell & Bioscience Sep 2023Menin is a scaffold protein encoded by the Men1 gene, which interacts with various transcriptional proteins to activate or repress cellular processes and is a key...
BACKGROUND
Menin is a scaffold protein encoded by the Men1 gene, which interacts with various transcriptional proteins to activate or repress cellular processes and is a key mediator in multiple organs. Both liver-specific and hepatocyte-specific Menin deficiency promotes high-fat diet-induced liver steatosis in mice, as well as insulin resistance and type 2 diabetic phenotype. The potential link between Menin and hepatic metabolism homeostasis may provide new insights into the mechanism of fatty liver disease.
RESULTS
Disturbance of hepatic Menin expression impacts metabolic pathways associated with non-alcoholic fatty liver disease (NAFLD), including the FoxO signaling pathway, which is similar to that observed in both oleic acid-induced fatty hepatocytes model and biopsied fatty liver tissues, but with elevated hepatic Menin expression and inhibited FABP1. Higher levels of Menin facilitate glucose uptake while restraining fatty acid uptake. Menin targets the expression of FABP3/4/5 and also CD36 or GK, PCK by binding to their promoter regions, while recruiting and deploying the cellular localization of PPARγ and SIRT1 in the nucleus and cytoplasm. Accordingly, Menin binds to PPARγ and/or FoxO1 in hepatocytes, and orchestrates hepatic glucose and fatty acid uptake by recruiting SIRT1.
CONCLUSION
Menin plays an orchestration role as a transcriptional activator and/or repressor to target downstream gene expression levels involved in hepatic energy uptake by interacting with the cellular energy sensor SIRT1, PPARγ, and/or FoxO1 and deploying their translocations between the cytoplasm and nucleus, thereby maintaining metabolic homeostasis. These findings provide more evidence suggesting Menin could be targeted for the treatment of hepatic steatosis, NAFLD or metabolic dysfunction-associated fatty liver disease (MAFLD), and even other hepatic diseases.
PubMed: 37740216
DOI: 10.1186/s13578-023-01119-y -
Foods (Basel, Switzerland) Nov 2023This study is based on the fatty acid and amino acid profiles of seven edible insect species: , , , , , and . The aim of the present study is to provide new data on the...
This study is based on the fatty acid and amino acid profiles of seven edible insect species: , , , , , and . The aim of the present study is to provide new data on the fatty acid distributions among lipid classes as well as the species-specific protein conversion factor (Kp) of a wide range of insects in order to further improve the nutritional characterisation of insects as food. Oleic acid was the predominant fatty acid in all insects except for , in which a significantly higher percentage of linoleic acid was found. The majority of the lipids were neutral lipids. A significant amount of α-linolenic acid in the phospholipid fraction of was shown, while in phospholipids were the only fraction in which a measurable amount of docosahexaenoic acid was found. Overall, in most insects, the phospholipid fraction had the highest polyunsaturated fatty acid content compared to the other classes, which may be protective in terms of auto-oxidative stability. Kp values in the range of 4.17 to 6.43 were obtained. Within the nutritional quality indices, all insects showed healthy fatty acids and high-quality amino acid profiles.
PubMed: 38002148
DOI: 10.3390/foods12224090 -
Nutrients Oct 2023Acylethanolamides (NAEs) are bioactive lipids derived from diet fatty acids that modulate important homeostatic functions, including appetite, fatty acid synthesis,...
Acylethanolamides (NAEs) are bioactive lipids derived from diet fatty acids that modulate important homeostatic functions, including appetite, fatty acid synthesis, mitochondrial respiration, inflammation, and nociception. Among the naturally circulating NAEs, the pharmacology of those derived from either arachidonic acid (Anandamide), oleic acid (OEA), and palmitic acid (PEA) have been extensively characterized in diet-induced obesity. For the present work, we extended those studies to linoleoylethanolamide (LEA), one of the most abundant NAEs found not only in plasma and body tissues but also in foods such as cereals. In our initial study, circulating concentrations of LEA were found to be elevated in overweight humans (body mass index (BMI, Kg/m) > 25) recruited from a representative population from the south of Spain, together with AEA and the endocannabinoid 2-Arachidonoyl glycerol (2-AG). In this population, LEA concentrations correlated with the circulating levels of cholesterol and triglycerides. In order to gain insight into the pharmacology of LEA, we administered it for 14 days (10 mg/kg i.p. daily) to obese male Sprague Dawley rats receiving a cafeteria diet or a standard chow diet for 12 consecutive weeks. LEA treatment resulted in weight loss and a reduction in circulating triglycerides, cholesterol, and inflammatory markers such as Il-6 and Tnf-alpha. In addition, LEA reduced plasma transaminases and enhanced acetyl-CoA-oxidase (Acox) and Uncoupling protein-2 (Ucp2) expression in the liver of the HFD-fed animals. Although the liver steatosis induced by the HFD was not reversed by LEA, the overall data suggest that LEA contributes to the homeostatic signals set in place in response to diet-induced obesity, potentially contributing with OEA to improve lipid metabolism after high fat intake. The anti-inflammatory response associated with its administration suggests its potential for use as a nutrient supplement in non-alcoholic steatohepatitis.
Topics: Rats; Humans; Animals; Male; Rats, Sprague-Dawley; Obesity; Liver; Non-alcoholic Fatty Liver Disease; Diet, High-Fat; Weight Gain; Inflammation; Triglycerides; Cholesterol; Dyslipidemias; Oleic Acid
PubMed: 37892524
DOI: 10.3390/nu15204448