-
Genomics, Proteomics & Bioinformatics Oct 2021Oleic acid (OA), a monounsaturated fatty acid (MUFA), has previously been shown to reverse saturated fatty acid palmitic acid (PA)-induced hepatic insulin resistance...
Oleic acid (OA), a monounsaturated fatty acid (MUFA), has previously been shown to reverse saturated fatty acid palmitic acid (PA)-induced hepatic insulin resistance (IR). However, its underlying molecular mechanism is unclear. In addition, previous studies have shown that eicosapentaenoic acid (EPA), a ω-3 polyunsaturated fatty acid (PUFA), reverses PA-induced muscle IR, but whether EPA plays the same role in hepatic IR and its possible mechanism involved need to be further clarified. Here, we confirmed that EPA reversed PA-induced IR in HepG2 cells and compared the proteomic changes in HepG2 cells after treatment with different free fatty acids (FFAs). A total of 234 proteins were determined to be differentially expressed after PA+OA treatment. Their functions were mainly related to responses to stress and endogenous stimuli, lipid metabolic process, and protein binding. For PA+EPA treatment, the PA-induced expression changes of 1326 proteins could be reversed by EPA, 415 of which were mitochondrial proteins, with most of the functional proteins involved in oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle. Mechanistic studies revealed that the protein encoded by JUN and reactive oxygen species (ROS) play a role in OA- and EPA-reversed PA-induced IR, respectively. EPA and OA alleviated PA-induced abnormal adenosine triphosphate (ATP) production, ROS generation, and calcium (Ca) content. Importantly, HO-activated production of ROS increased the protein expression of JUN, further resulting in IR in HepG2 cells. Taken together, we demonstrate that ROS/JUN is a common response pathway employed by HepG2 cells toward FFA-regulated IR.
Topics: Eicosapentaenoic Acid; Hep G2 Cells; Humans; Hydrogen Peroxide; Insulin Resistance; Oleic Acid; Palmitic Acid; Proteomics; Reactive Oxygen Species
PubMed: 33631425
DOI: 10.1016/j.gpb.2019.06.005 -
Cell Chemical Biology Feb 2024Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines,...
Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (PPAR-α antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR-α functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.
Topics: Animals; Mice; Caenorhabditis elegans; Ferroptosis; Oleic Acid; Peroxisome Proliferator-Activated Receptors; Iron Overload; Iron; Phospholipid Ethers
PubMed: 37944523
DOI: 10.1016/j.chembiol.2023.10.012 -
Phytotherapy Research : PTR Feb 2020The use of vegetable butters and oils shows promising results in the treatment of skin wounds, as they have an effective impact on the phases of the wound-healing... (Review)
Review
The use of vegetable butters and oils shows promising results in the treatment of skin wounds, as they have an effective impact on the phases of the wound-healing process through their antimicrobial, anti-inflammatory, and antioxidative activities and by promoting cell proliferation, increasing collagen synthesis, stimulating dermal reconstruction, and repairing the skin's lipid barrier function. In this article, in vitro and in vivo studies of argan (Argania spinosa), avocado (Persea americana), black cumin (Nigella sativa), calophyllum (Calophyllum inophyllum), coconut (Cocos nucifera), cranberry (Vaccinium macrocarpon), grape (Vitis vinifera), green coffee (Coffea arabica), lentisk (Pistacia lentiscus), linseed (Linum usitatissimum), lucuma (Pouteria lucuma), mango (Mangifera indica), olive (Olea europaea), pomegranate (Punica granatum), pumpkin (Cucurbita pepo), rapeseed (Brassica napus), sea buckthorn (Hippophae rhamnoides), and sunflower (Helianthus annuus) oils were reviewed. In many cases, vegetable oils proved to be more effective than synthetic wound-healing compounds used as controls. The fatty-acid components of vegetable oils are assumed to play a major role in the wound-healing process, in particular polyunsaturated fatty acids such as linoleic acid. Evidence shows that oils with a higher linoleic to oleic acid ratio are more effective for lipid barrier repair. However, in depth studies are needed to gain knowledge about vegetable oils' effects on the skin and vice versa.
Topics: Administration, Cutaneous; Animals; Calophyllum; Cucurbita; Dermatology; Fatty Acids; Flax; Humans; Linoleic Acid; Linseed Oil; Mangifera; Oleic Acid; Persea; Plant Oils; Skin; Skin Diseases; Vaccinium macrocarpon; Vegetables; Wound Healing
PubMed: 31657094
DOI: 10.1002/ptr.6524 -
Nature Immunology Jan 2024The nature of activation signals is essential in determining T cell subset differentiation; however, the features that determine T cell subset preference acquired during...
The nature of activation signals is essential in determining T cell subset differentiation; however, the features that determine T cell subset preference acquired during intrathymic development remain elusive. Here we show that naive CD4 T cells generated in the mouse thymic microenvironment lacking Scd1, encoding the enzyme catalyzing oleic acid (OA) production, exhibit enhanced regulatory T (T) cell differentiation and attenuated development of experimental autoimmune encephalomyelitis. Scd1 deletion in K14 thymic epithelia recapitulated the enhanced T cell differentiation phenotype of Scd1-deficient mice. The dearth of OA permitted DOT1L to increase H3K79me2 levels at the Atp2a2 locus of thymocytes at the DN2-DN3 transition stage. Such epigenetic modification persisted in naive CD4 T cells and facilitated Atp2a2 expression. Upon T cell receptor activation, ATP2A2 enhanced the activity of the calcium-NFAT1-Foxp3 axis to promote naive CD4 T cells to differentiate into T cells. Therefore, OA availability is critical for preprogramming thymocytes with T cell differentiation propensities in the periphery.
Topics: Animals; Mice; Thymocytes; Oleic Acid; Thymus Gland; T-Lymphocytes, Regulatory; Cell Differentiation; Forkhead Transcription Factors
PubMed: 38062135
DOI: 10.1038/s41590-023-01672-1 -
Biomolecules Aug 2020α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4-5), Ca-binding protein. α-LA is a regulatory component of lactose synthase enzyme system functioning in the... (Review)
Review
α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4-5), Ca-binding protein. α-LA is a regulatory component of lactose synthase enzyme system functioning in the lactating mammary gland. The protein possesses a single strong Ca-binding site, which can also bind Mg, Mn, Na, K, and some other metal cations. It contains several distinct Zn-binding sites. Physical properties of α-LA strongly depend on the occupation of its metal binding sites by metal ions. In the absence of bound metal ions, α-LA is in the molten globule-like state. The binding of metal ions, and especially of Ca, increases stability of α-LA against the action of heat, various denaturing agents and proteases, while the binding of Zn to the Ca-loaded protein decreases its stability and causes its aggregation. At pH 2, the protein is in the classical molten globule state. α-LA can associate with membranes at neutral or slightly acidic pH at physiological temperatures. Depending on external conditions, α-LA can form amyloid fibrils, amorphous aggregates, nanoparticles, and nanotubes. Some of these aggregated states of α-LA can be used in practical applications such as drug delivery to tissues and organs. α-LA and some of its fragments possess bactericidal and antiviral activities. Complexes of partially unfolded α-LA with oleic acid are cytotoxic to various tumor and bacterial cells. α-LA in the cytotoxic complexes plays a role of a delivery carrier of cytotoxic fatty acid molecules into tumor and bacterial cells across the cell membrane. Perhaps in the future the complexes of α-LA with oleic acid will be used for development of new anti-cancer drugs.
Topics: Animals; Antineoplastic Agents; Humans; Hydrogen-Ion Concentration; Lactalbumin; Neoplasms; Oleic Acid
PubMed: 32825311
DOI: 10.3390/biom10091210 -
Journal of Pharmaceutical and... Sep 2021Oleic acid is a pharmaceutical excipient and has been widely used in many dosage forms. It remains unclear in terms of the fatty acids (FAs) profile. In this study, a...
Oleic acid is a pharmaceutical excipient and has been widely used in many dosage forms. It remains unclear in terms of the fatty acids (FAs) profile. In this study, a sensitive and direct method based on high-performance liquid chromatography coupled with charged aerosol detector (HPLC-CAD) was developed to study the compositions of oleic acid. The chromatographic conditions were optimized to achieve good separation and high sensitivity. The components of oleic acid were identified by ion trap/time of flight mass spectrometry (MS-IT-TOF). Twenty-seven FAs were identified based on the exact mass-to-charge ratio and fragments, among which 13 FAs were confirmed with the reference standards. Nine FAs in the oleic acid samples including oleic acid, linolenic acid, myristic acid, palmitoleic acid, linoleic acid, palmitic acid, stearic acid, arachidic acid and behenic acid were simultaneously determined by the developed HPLC-CAD, which showed good linearity with r>0.999. The limit of detection (LOD) and limit of quantification (LOQ) of 9 FAs were 0.006-0.1 μg mL and 0.032-0.22 μg mL, respectively. The components with concentration level not less than 0.03 % (referring to the sample concentration of 1.0 mg mL) can be quantified. The mean recovery values of 9 FAs ranged from 96.5%-103.6% at three concentration levels of 80 %, 100 % and 120 %. The repeatability and intermediate precision were less than 5.0 % for oleic acid and components with concentration levels more than 0.05 %. In contrast to the conventional pre-column derivatization gas chromatography (GC), HPLC-CAD could unbiasedly and directly detect more components, especially the FAs with long carbon chains. Overall, the developed novel HPLC-CAD method can ameliorate the deficiency of the indirect GC method recorded in current pharmacopeias, thus having great potential for the comprehensive understanding and quality control of oleic acid.
Topics: Aerosols; Chromatography, High Pressure Liquid; Fatty Acids; Gas Chromatography-Mass Spectrometry; Oleic Acid
PubMed: 34273659
DOI: 10.1016/j.jpba.2021.114238 -
Journal of Food Biochemistry May 2022Coordinated effects of glucose and oleic acid on glucagon-like peptide-1 (GLP-1) mediated differentiation of insulin-positive differentiating umbilical cord mesenchymal...
Coordinated effects of glucose and oleic acid on glucagon-like peptide-1 (GLP-1) mediated differentiation of insulin-positive differentiating umbilical cord mesenchymal stromal cells (dUCBMSCs) was studied using a co-culture of NCI-H716 (GLP-1+) and UCBMSCs (insulin+). The addition of 2.5 mM glucose increased the proliferation of NCI-H716 cells by 30% and induced transformation of UCBMSCs into insulin-secreting cells in 18 days as compared to 22 days in control cells. Oleic acid (25 μM) showed decrease in cell proliferation, autophagy, and apoptosis in NCI-H716 cells while no effect was observed in dUCBMSCs. Prolonged glucose and oleic acid resulted in apoptosis and cell cycle changes in dUCBMSCs after day 18 while higher concentrations resulted in cell death. Additionally, the expression of FAS and ACC mRNA was observed in NCI-H716 and dUCBMSCs post 24-hr addition of glucose and/or oleic acid. Absorption of oleic acid was high in NCI-H716 compared to dUCBMSCs. Taken together, optimal concentrations of glucose and oleic acid could be a key factor in stimulating intrinsic GLP-1, which in turn stimulates differentiating MSCs in a glucose-dependent manner. PRACTICAL APPLICATIONS: The aim of this article was to study whether differentiating or differentiated MSCs after mobilization or post-transplant would require optimal glucose and oleic acid to naturally stimulate intrinsic GLP-1, or otherwise, the high or long-term overload of glucose or oleic acid could result in inhibition of differentiated cells resulting in failure of insulin secretion.
Topics: Cell Line; Glucagon-Like Peptide 1; Glucose; Insulin; Oleic Acid
PubMed: 35246864
DOI: 10.1111/jfbc.14087 -
Time-Dependent Differences in the Effects of Oleic Acid and Oleyl Alcohol on the Human Skin Barrier.Molecular Pharmaceutics Dec 2023Oleic acid and oleyl alcohol are commonly used permeation and penetration enhancers to facilitate topical drug delivery. Here, we aimed to better understand the...
Oleic acid and oleyl alcohol are commonly used permeation and penetration enhancers to facilitate topical drug delivery. Here, we aimed to better understand the mechanism of their enhancing effects in terms of their interactions with the human skin barrier using diclofenac diethylamine (DIC-DEA), a nonsteroidal anti-inflammatory drug for topical pain management. Oleic acid promoted DIC-DEA permeation through ex vivo human skin more rapidly than oleyl alcohol (both applied at 0.75%) due to fluidization of stratum corneum lipids as revealed by infrared spectroscopy. After 12 h, the effect of these enhancers on DIC-DEA permeation leveled off, fluidization was no longer evident, and skin permeabilization was mainly due to the formation of fluid enhancer-rich domains. Contrary to oleyl alcohol, oleic acid adversely affected two indicators of the skin barrier integrity, transepidermal water loss and skin electrical impedance. The content of oleyl alcohol in the stratum corneum was lower than that of oleic acid (even 12 h after the enhancers were removed from the skin surface), but it caused higher DIC-DEA retention in both epidermis and dermis compared to oleic acid. The effects of oleyl alcohol and oleic acid on DIC-DEA permeation and retention in the skin were similar after a single and repeated application (4 doses every 12 h). Thus, oleyl alcohol offers several advantages over oleic acid for topical drug delivery.
Topics: Humans; Oleic Acid; Skin Absorption; Skin; Fatty Alcohols; Administration, Cutaneous
PubMed: 37950377
DOI: 10.1021/acs.molpharmaceut.3c00648 -
Current Opinion in Chemical Biology Oct 2022Raman microscopy has been used to deduce information about the distributions of endogenous biomolecules without exogenous labeling. Several functional groups, such as... (Review)
Review
Raman microscopy has been used to deduce information about the distributions of endogenous biomolecules without exogenous labeling. Several functional groups, such as alkynes (CC), nitriles (CN), and carbon-deuterium (C-D) bonds, have been employed in recent years as Raman tags to detect target molecules in cells. In this article, we review some recent advances in applications using deuterated fatty acids for lipid analysis, such as investigation of tumor-selective cytotoxicity of γ-linolenic acid (GLA), simultaneous two-color imaging of stearate and oleate using deuterated and protonated alkynes, Raman hyperspectral imaging, and analyses of the physical properties of lipids through spectral unmixing of the C-D vibrational frequencies. In addition, we review some advanced methods for observing intracellular metabolic activities, such as de novo lipogenesis from deuterium-labeled precursors.
Topics: Alkynes; Carbon; Deuterium; Fatty Acids; Nitriles; Oleic Acid; Spectrum Analysis, Raman; Stearates; gamma-Linolenic Acid
PubMed: 35792373
DOI: 10.1016/j.cbpa.2022.102181 -
Free Radical Biology & Medicine Jun 2023Haemolysis of erythrocytes upon exposure to haemato-toxic phenylhydrazine (PHZ), makes it an experimental model of anaemia and a partial model of β-thalassaemia, where...
Haemolysis of erythrocytes upon exposure to haemato-toxic phenylhydrazine (PHZ), makes it an experimental model of anaemia and a partial model of β-thalassaemia, where oxidative stress (OS) was identified as principal causative factor. Oleic acid (OA) was evidenced to ameliorate such stress with antioxidative potential. Erythrocytes were incubated in vitro using 1 mM PHZ, 0.06 nM OA. Erythrocyte membrane protein densities and haemoglobin (Hb) status were examined. Any interaction of Hb with PHZ/OA was checked by calorimetric and spectroscopic analysis using pure molecules. Occurrence of erythrocyte apoptosis and involvement of free iron in all groups were evaluated. PHZ exposure to erythrocytes results in OS with subsequent apoptosis as evidenced from increased lipid peroxidation and translocation of phosphatidylserine in outer membrane. Preservations of erythrocyte cytoskeletal architecture and membrane bound enzyme activity were found in presence of OA. Moreover, both heme and globin of Hb was examined to be conserved by OA. Presence of OA, impeded apoptosis also, possibly by thwarting Hb breakdown followed by free iron release and consequent free radical generation. Additionally, direct sequential binding of OA with PHZ endorsed another protective mechanism of OA toward erythrocytes. OA affords protection to erythrocytes by conserving its major components and prevents haemolysis which project OA as a haemato-protective agent. Apart from combating PHZ toxicity, anti-apoptotic action of OA strongly suggests its usage in anaemia and β-thalassaemia patients to curb irreversible erythrocyte breakdown. This research strongly recommends OA in pure form or from dietary sources as a therapeutic against haemolytic disorders.
Topics: Humans; beta-Thalassemia; Oleic Acid; Membrane Proteins; Hemolysis; Erythrocytes; Hemoglobins; Iron
PubMed: 36965537
DOI: 10.1016/j.freeradbiomed.2023.03.019