-
Biomedicines Dec 2023Very little is known about the association between individual serum free fatty acids (FFAs) and clinical and laboratory parameters (indicators of heart failure severity)...
Very little is known about the association between individual serum free fatty acids (FFAs) and clinical and laboratory parameters (indicators of heart failure severity) in acute heart failure (AHF) patients. Here, the baseline serum levels of FFAs, 16:0 (palmitic acid), 16:1 (palmitoleic acid), 18:0 (stearic acid), 18:1 (oleic acid), 18:2 (linoleic acid), 18:3 (alpha-linolenic acid or gamma-linolenic acid), 20:4 (arachidonic acid), 20:5 (eicosapentaenoic acid), and 22:6 (docosahexaenoic acid), were determined in 304 AHF patients (94.7% belonged to New York Heart Association functional class IV) using gas chromatography. Spearman correlation coefficients were used to examine the associations between the individual and total (the sum of all FFAs) FFAs and clinical and laboratory parameters. After applying a Bonferroni correction to correct for multiple testing, the total FFAs, as well as the individual FFAs (except FFAs 18:0, 20:5, and 22:6), were found to be significantly positively correlated with serum albumin. Only a few additional associations were found: FFA 16:0 was significantly negatively correlated with systolic pulmonary artery pressure, FFA 18:3 was significantly negatively correlated with C-reactive protein and body mass index, and FFA 20:4 was significantly negatively correlated with blood urea nitrogen. Based on our results, we conclude that in patients with severe AHF, individual and total serum FFAs are slightly associated with established laboratory and clinical parameters, which are indicators of heart failure severity.
PubMed: 38137418
DOI: 10.3390/biomedicines11123197 -
European Journal of Pharmacology Dec 2023Peroxisome proliferator-activated receptors (PPARs) are currently among the most focused-on therapeutic targets for non-alcoholic steatohepatitis (NASH), although no...
BACKGROUND & AIMS
Peroxisome proliferator-activated receptors (PPARs) are currently among the most focused-on therapeutic targets for non-alcoholic steatohepatitis (NASH), although no clinical transformation has been achieved to date. In this study, we aimed to evaluate the effects of GW9662 on choline-deficient, L-amino acid-defined high-fat diet (CDAA-HFD)-induced NASH mice and reveal the mechanism underlying this effect.
METHODS
GW9662 (1 mg/kg) was administered in CDAA-HFD mouse model of NASH. The effect of GW9662 on hepatic lipid metabolism was investigated using liver RNA-seq and HepG2 cells induced by oleic acid and palmitic acid. In addition, 16S rRNA gene sequencing was performed to analyze the effects of GW9662 on the composition and function of the fecal microbiota.
RESULTS
GW9662 improved the CDAA-HFD caused elevation in the levels of ALT, AST, hepatic free fatty acids and triglycerides. The liver pathological analysis indicated that GW9662 alleviated the hepatic steatosis and fibrosis. The NAFLD activity score and RNA-Seq revealed that GW9662 mainly regulated the fatty acids transport and lipid synthesis by inhibiting PPARγ, CD36, FABP1, FASN, and SCD1, and through the up-regulation of PPARα. Moreover, GW9662 reduced the epididymal fat weight. GW9662 reversed the gut microbiota disorder by increasing the abundance of the beneficial bacteria Dubosiella and Lactobacillus and decreasing the abundance of harmful bacteria Lachnospiraceae_NK4A136_group, Helicobacteraceae, Desulfovibriaceae, and Rickenaceae.
CONCLUSIONS
GW9662 ameliorated lipid metabolism by inhibiting the PPARγ/CD36 pathway and altering the composition of the gut microbiota in NASH mice. Therefore, the PPARγ antagonist GW9662 deserves more attention as a potential therapeutic agent for NASH.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; PPAR gamma; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Liver; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 37838102
DOI: 10.1016/j.ejphar.2023.176113 -
Foods (Basel, Switzerland) Nov 2023This study analyzed and evaluated the basic crude fat contents, crude protein contents, phenolic compounds, lipid compositions (fatty acids, phytosterols, and...
This study analyzed and evaluated the basic crude fat contents, crude protein contents, phenolic compounds, lipid compositions (fatty acids, phytosterols, and tocopherols), and amino acid compositions of 26 walnut samples from 11 walnut-growing provinces in China. The results indicate that the oil contents of the samples varied from 60.08% to 71.06%, and their protein contents ranged from 7.26 g/100 g to 19.50 g/100 g. The composition of fatty acids corresponded to palmitic acid at 4.61-8.27%, stearic acid at 1.90-3.55%, oleic acid at 15.50-32.28%, linoleic acid at 53.44-67.64%, and α-linolenic acid at 2.45-12.77%. The samples provided micronutrients in widely varying amounts, including tocopherol, phytosterol, and total phenolic content, which were found in the walnut oil samples in amounts ranging from 356.49 to 930.43 mg/kg, from 1248.61 to 2155.24 mg/kg, and from 15.85 to 68.51 mg/kg, respectively. A comprehensive evaluation of walnut oil quality in the samples from the 11 provinces using a principal component analysis was conducted. The findings revealed that the samples from Henan, Gansu, and Zhejiang had the highest composite scores among all provinces. Overall, Yunnan-produced walnuts had high levels of crude fat, polyunsaturated fatty acids, and total tocopherols, making them more suitable for producing high-quality oil, whereas Henan-produced walnuts, although lower in crude fat, had a higher crude protein content and composite score, thus showing the best walnut characteristics.
PubMed: 38002181
DOI: 10.3390/foods12224123 -
ACS Applied Bio Materials Dec 2023This study presents the successful development of printable-microencapsulated ascorbic acid (AA) for personalized topical delivery using laser printing technology. Rice...
This study presents the successful development of printable-microencapsulated ascorbic acid (AA) for personalized topical delivery using laser printing technology. Rice flour with a 10% AA content was selected as an encapsulation material. Hydrophobic nanosilica was used to create negative electrostatic charges on the microencapsulated surfaces via a high-speed mixture. This process facilitated the microencapsulated AA fabrication using a commercial laser printer and produced a well-patterned design with some minor print defects, such as banding and scattering. The amount of encapsulated AA per area was 0.28 mg/cm, and the RGB color code was 0,0,0. An emulsion carrier system comprising pentylene glycol (P5G) or diethylene glycol monoethyl ether (DEGEE), Tween 20, oleic acid, and deionized (DI) water at a ratio of 20:30:30:20 was developed to enhance AA transmission into the skin. The Franz diffusion cell technique was used to investigate topical absorption on Strat-M membranes using P5G and DEGEE as enhancers. The steady-state fluxes were 8.40 (±0.64) and 10.04 (±0.58) μg/h/cm for P5G and DEGEE, respectively. Cytotoxicity tests conducted on fibroblast cells revealed low cytotoxicity for the encapsulation products and carriers.
Topics: Ascorbic Acid; Skin
PubMed: 37981740
DOI: 10.1021/acsabm.3c00648 -
Biological Research May 2024We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the...
BACKGROUND
We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed.
RESULTS
We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts.
CONCLUSIONS
For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.
Topics: Oleic Acid; Myotonic Dystrophy; Humans; Cell Differentiation; MicroRNAs; Autophagy; Cell Line; RNA-Binding Proteins
PubMed: 38760841
DOI: 10.1186/s40659-024-00496-z -
Life (Basel, Switzerland) Apr 2024Olive oil () is one of the major components of the Mediterranean diet and is composed of a greater percentage of monounsaturated fatty acids, such as oleic acid;... (Review)
Review
Olive oil () is one of the major components of the Mediterranean diet and is composed of a greater percentage of monounsaturated fatty acids, such as oleic acid; polyunsaturated fatty acids, such as linoleic acid; and minor compounds, such as phenolic compounds, and particularly hydroxytyrosol. The latter, in fact, are of greater interest since they have found widespread use in popular medicine. In recent years, it has been documented that phenolic acids and in particular hydroxytyrosol have anti-inflammatory, antioxidant, and antiproliferative action and therefore interest in their possible use in clinical practice and in particular in neoplasms, both solid and hematological, has arisen. This work aims to summarize and analyze the studies present in the literature, both in vitro and in vivo, on the possible use of minor components of olive oil in some hematological neoplasms. In recent years, in fact, interest in nutraceutical science has expanded as a possible adjuvant in the treatment of neoplastic pathologies. Although it is worth underlining that, regarding the object of our study, there are still few preclinical and clinical studies, it is, however, possible to document a role of possible interest in clinical practice.
PubMed: 38792604
DOI: 10.3390/life14050583 -
The Journal of Nutrition Aug 2023Higher dietary quality is associated with lower disease risks and has not been examined extensively with lipidomic profiles.
BACKGROUND
Higher dietary quality is associated with lower disease risks and has not been examined extensively with lipidomic profiles.
OBJECTIVES
Our goal was to examine associations of the Healthy Eating Index (HEI)-2015, Alternate HEI-2010 (AHEI-2010), and alternate Mediterranean Diet Index (aMED) diet quality indices with serum lipidomic profiles.
METHODS
We conducted a cross-sectional analysis of HEI-2015, AHEI-2010, and aMED with lipidomic profiles from 2 nested case-control studies within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 627) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 711). We used multivariable linear regression to determine associations of the indices, derived from baseline food-frequency questionnaires (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: 1993-2001, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: 1985-1988) with serum concentrations of 904 lipid species and 252 fatty acids (FAs) across 15 lipid classes and 28 total FAs, within each cohort and meta-analyzed results using fixed-effect models for lipids significant at Bonferroni-corrected threshold in common in both cohorts.
RESULTS
Adherence to HEI-2015, AHEI-2010, or aMED was associated positively with 31, 41, and 54 lipid species and 8, 6, and 10 class-specific FAs and inversely with 2, 8, and 34 lipid species and 1, 3, and 5 class-specific FAs, respectively. Twenty-five lipid species and 5 class-specific FAs were common to all indices, predominantly triacylglycerols, FA22:6 [docosahexaenoic acid (DHA)]-containing species, and DHA. All indices were positively associated with total FA22:6. AHEI-2010 and aMED were inversely associated with total FA18:1 (oleic acid) and total FA17:0 (margaric acid), respectively. The identified lipids were most associated with components of seafood and plant proteins and unsaturated:saturated fat ratio in HEI-2015; eicosapentaenoic acid plus DHA in AHEI-2010; and fish and monounsaturated:saturated fat ratio in aMED.
CONCLUSIONS
Adherence to HEI-2015, AHEI-2010, and aMED is associated with serum lipidomic profiles, mostly triacylglycerols or FA22:6-containing species, which are related to seafood and plant proteins, eicosapentaenoic acid-DHA, fish, or fat ratio index components.
Topics: Male; Animals; United States; Humans; Female; Lipidomics; Smokers; Finland; Cross-Sectional Studies; alpha-Tocopherol; beta Carotene; Eicosapentaenoic Acid; Diet; Diet, Mediterranean; Triglycerides; Colorectal Neoplasms; Ovarian Neoplasms
PubMed: 37328109
DOI: 10.1016/j.tjnut.2023.06.010 -
Cell Research Mar 2024Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by...
Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by combining structural approach (including cryo-electron microscopy), mass spectrometry analysis, and functional studies, we identify oleic acid (OA) as an endogenous ligand of GPR3. Our study reveals a hydrophobic tunnel within GPR3 that connects the extracellular side of the receptor to the middle of plasma membrane, enabling fatty acids to readily engage the receptor. Functional studies demonstrate that OA triggers downstream G signaling, whereas lysophospholipids fail to activate the receptor. Moreover, our research reveals that cold stimulation induces the secretion of OA in mice, subsequently activating G/cAMP/PKA signaling in brown adipose tissue. Notably, brown adipose tissues from Gpr3 knockout mice do not respond to OA during cold stimulation, reinforcing the significance of GPR3 in this process. Finally, we propose a "born to be activated and cold to enhance" model for GPR3 activation. Our study provides a starting framework for the understanding of GPR3 signaling in cold-stimulated thermogenesis.
Topics: Animals; Mice; Adipose Tissue, Brown; Cell Membrane; Cryoelectron Microscopy; Ligands; Mice, Knockout; Oleic Acid; Receptors, G-Protein-Coupled
PubMed: 38287117
DOI: 10.1038/s41422-024-00932-5 -
Journal of Colloid and Interface Science Jan 2024Surface tension gradient driven Marangoni flows originating from multiple sources are important to many industrial and medical applications, but the theoretical...
HYPOTHESIS
Surface tension gradient driven Marangoni flows originating from multiple sources are important to many industrial and medical applications, but the theoretical literature focuses on single surfactant sources. Understanding how two spreading surfactant sources interact allows insights from single source experiments to be applied to multi-source applications. Two key features of multi-source spreading - source translation and source deformation - can be explained by transport modeling of a two-source system.
MODELING
Numerical simulations of two oleic acid disks placed at varying initial separation distances on a glycerol subphase were performed using COMSOL Multiphysics and compared to spreading of a single surfactant source.
FINDINGS
Interaction of two spreading sources can be split into three regimes: the independent regime - where each source is unaffected by the other, the interaction regime - where the presence of a second source alters one or more features of the spreading dynamics, and the quasi-one disk regime - where the two sources merge together. The translation of the sources, manifested as increasing separation distance between disk centers of mass, is driven by the flow fields within the subphase and the resultant surface deformation, while deformation of the sources occurs only once the surfactant fronts of the two sources meet.
PubMed: 37757714
DOI: 10.1016/j.jcis.2023.09.109 -
Molecules (Basel, Switzerland) Dec 2023Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for...
Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (, , , ) were designed and synthesized. The target product (compound ) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.
Topics: Humans; Lipid Metabolism; PPAR alpha; Carnitine O-Palmitoyltransferase; Non-alcoholic Fatty Liver Disease; Antipsychotic Agents; Ethylamines; Oleic Acid; Lipase; Indoles
PubMed: 38202597
DOI: 10.3390/molecules29010012