Search Results (286)

Background: Microglial metabolic reprogramming drives neuroinflammation in Diabetes-associated cognitive dysfunction (DACD). This study aims to evaluate Buwang formula (BWF) effects on diabetic neuroinflammation and microglial metabolism. Methods: The chemical constituents present in BWF-containing cerebrospinal fluid (BWF-CCSF) were profiled by UHPLC-MS/MS, and putative targets were predicted via network pharmacology analysis. Diabetic db/db mice were treated with BWF, and behavioral, biochemical, and histopathological assessments were performed. The in vivo findings were further validated in BV2 cells exposed to high glucose (HG) and palmitic acid (PA). Cellular energy metabolism analysis was used to quantify dynamic changes in oxidative phosphorylation (OXPHOS) and glycolysis in BV2 cells, while flow cytometry and immunofluorescence were used to examine BV2 cell polarization. The expression levels of pathway-related proteins were examined by Western blot analysis. Results: A total of 15 chemical components were identified in BWF-CCSF. According to the network pharmacology prediction, the mTOR/HIF-1α pathway might participate in the effects exerted by BWF compounds that enter the brain. In diabetic mice, BWF notably suppressed the expression of pro-inflammatory factors and reduced the accumulation of pathological proteins within the hippocampal tissue, which improved learning and memory impairments, and these improvements were accompanied by suppressed activation of the mTOR/HIF-1α pathway and its downstream glycolysis. In BV2 cells exposed to HG and PA, BWF-CCSF treatment significantly increased OXPHOS and inhibited glycolysis, promoting a polarization toward M2 anti-inflammatory phenotype. Conclusions: BWF regulates microglial metabolic reprogramming and attenuates neuroinflammation, effects that are associated with modulation of the mTOR/HIF-1α pathway, and these findings suggest that BWF warrants further investigation as a potential therapeutic candidate for DACD. Full article

Type 2 diabetes mellitus (T2D) is associated with dyslipidemia, characterized by elevated plasmatic triglycerides and free fatty acids, particularly palmitate (PA), which may cause lipotoxicity in skeletal muscle cells. This leads to inflammation, activation of the unfolded protein response (UPR), insulin resistance, and cell death. Herbal medicines such as Uncaria tomentosa (UT) have shown potential as complementary treatments for T2D due to their protective effects. Purpose and study design: This study investigates the effect of UT aqueous extract on UPR and insulin resistance induced by PA in C2C12 myotubes. C2C12 myoblasts were grown in DMEM medium supplemented with 10% fetal bovine serum and differentiated into myotubes with 3.5% horse serum. The myotubes were incubated with 100 or 500 μM PA, 2–100 µM thapsigargin (Tg) or tunicamycin (Tn), in the presence or absence of 250 μg/mL UT extract or 100 µM TUDCA, for 2 or 6 h. The myotubes treated with UT extract for 6 h, after the incubation with 20 µM Tg, Tn or 500 µM PA, presented reduction in the expression of UPR-related genes ATF4 and CHOP by approximately 1.5-fold, and increased by 3-fold the expression of IRS-1, an insulin-signaling protein, when compared to myotubes incubated with only 20 µM Tg, Tn or 500 µM PA. These findings suggest that UT extract may serve as a modulator against skeletal muscle dyslipidemia by downregulating ATF4 and CHOP, reducing cell stress and death, while enhancing IRS-1 expression, which supports the use of the UT extract in managing insulin resistance and T2D. Full article

Dysregulated lipid metabolism is a core pathogenic driver of type 2 diabetes. Honokiol (HKL), the major bioactive constituent of Magnolia officinalis, possesses anti-diabetic and lipid-regulatory properties. However, the underlying molecular mechanism remains elusive. This study investigates how HKL ameliorates high-glucose/high-fat (HGHF)-induced hepatic lipid accumulation, with a focus on the role of SIRT3-mediated deacetylation of peroxisome proliferator-activated receptor γ (PPARG). The core targets of HKL were identified through network pharmacology and molecular docking. Human hepatic MIHA cells were treated with glucose (Glu, 40 mM) and palmitic acid (0.2~0.3 mM PA) to establish a lipid accumulation model, followed by treatment with HKL (5–10 μM) with or without a confirmed selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). Lipid accumulation was assessed by Oil Red O staining and by measuring triglyceride (TG) and total cholesterol (TC) levels. Protein expression and the SIRT3-PPARG interaction were analyzed by Western blot and co-immunoprecipitation (Co-IP). SIRT3 and PPARG were identified as core targets of HKL, exhibiting strong binding with calculated energies of −6.834 and −6.579 kcal/mol, respectively. In MIHA cells, HGHF (40 mM Glu + 0.2–0.3 mM PA) induced lipid accumulation, including increased lipid droplets, and elevated TG (2.5–3.2-fold) and TC (2.2–2.8-fold) contents in a dose-dependent manner, accompanied by downregulated SIRT3/PPARG expression and heightened global protein acetylation. The non-cytotoxic HGHF-M condition (40 mM Glu + 0.2 mM PA) was selected for further experiments. HKL (5–10 μM) dose-dependently reduced lipid accumulation by ~38–60%, decreased TG and TC levels by up to ~13% and ~30%, and restored SIRT3/PPARG expression. The protective effects of HKL were reversed by inhibition of SIRT3 with 3-TYP. Co-IP confirmed the interaction between SIRT3 and PPARG, and SIRT3 overexpression significantly decreased the acetylation level of PPARG. This study suggests that HKL ameliorates hepatic lipid accumulation via SIRT3-mediated deacetylation of PPARG, providing an experimental basis for considering HKL as a potential therapeutic agent against metabolic disorders. Full article

Research on diabetic retinopathy (DR) usually emphasizes hyperglycemia and other causes like dyslipidemia, which are still not well understood. This study examined the effects of palmitic acid (PA) exposure, alone and combined with high glucose (G25), on Müller Glial Cell (MGC) dysfunction and angiogenic signaling. Primary MGC cultures were treated with G25 (25 mM), PA (250 µM), or PA + G25 for 24 and 48 h, followed by assessments of cell viability and analysis of the Vascular Endothelial Growth Factor (VEGFA)/VEGFA receptor 2 (VEGFR2) pathway through immunofluorescence, Western blot, and ELISA. Additionally, Gaussian mixture models (GMMs) were used to identify phenotypic subpopulations based on fluorescence intensity. The results showed that while hyperglycemia did not cause significant changes, PA and PA + G25 induced apoptosis-related cell death and significantly increased the expression of VEGFA, VEGFR2, HIF-α, and SP1. Although broad phenotypic diversity was observed at 24 h, by 48 h, a distinct shift towards an angiogenic phenotype was noted, with significantly elevated VEGFA/VEGFR2 levels. In summary, this research demonstrates that PA acts as a critical inducer of an angiogenic secretory phenotype in MGCs, indicating that lipid-mediated signaling plays a vital role in neovascularization in DR, possibly independent of glucose levels. Full article

The perception of the odor of fatty acids provides individuals with information about the nutritional content of foods. This perception varies depending on biological and genetic factors. Previous studies have shown that odorant binding proteins (OBPs) present in olfactory mucus play an important role in capturing and transporting odorants, typically lipophilic molecules, through the mucus to the olfactory receptors (ORs). The main objective of this research was to study the role of the rs2590498 (A/G) polymorphism of the human OBPIIa gene on the threshold and intensity of odor perception of palmitic (PA), oleic (OA) and linoleic (LA) acids. Volunteers were genotyped for OBP polymorphisms and classified as normosmic or hyposmic based on their threshold for n-butanol. The results show that normosmic or AA genotype participants perceived the odors of PA, OA, and LA at lower concentrations and with greater intensity than hyposmic or AG/GG genotype participants. Furthermore, the perception intensity reported by participants showed the following decreasing order: LA > OA > PA. These findings indicate that the intensity and threshold of perception depend on the lipophilicity of the molecule. These results indicate that genetic and biological factors, as well as the chemical properties of the molecules, play a key role in the olfactory perception of fatty acids. Full article

The phytopathogenic bacterium Pectobacterium carotovorum (Pcc) infects a wide range of crop plants and causes substantial economic losses. The authors of this study previously demonstrated that the selenium–arabinogalactan nanocomposite (Se/AG NC) is capable of mitigating the negative effects of infection of soybean seeds with Pcc during germination and can influence physiological and biochemical factors in the seedlings. This study investigated changes in the membrane fatty acid (FA) profile of soybean seedlings grown under different treatments and in control using chromatography–mass spectrometry (CMS). The soybean seed treatments included the following: (1) infection by Pcc alone; (2) nanopriming with Se/AG NC alone; and (3) infection by Pcc followed by nanopriming with Se/AG NC. The infection was performed by soaking seeds in a bacterial suspension. Nanopriming was performed by placing the seeds in an aqueous solution of Se/AG NC (6.25 µg/mL) with a Se concentration of 0.000625%. Then, the seeds were germinated over 5 days in the darkness at 25 °C. The FA profile of soybean seeds was characterized by 13 FAs dominated by linoleic (LA), linolenic (LNA), oleic (OA), palmitic (PA) and stearic (SA) acids. Se/AG NC nanopriming had no influence on the FA profile of soybean seeds. A unique FA profile of soybean seedlings was demonstrated. It consisted of 18 FAs containing 12 to 20 carbon atoms. The following FAs were dominant in the control samples: PA (28%), LA (32.8%), LNA (18.6%), and SA (7.5%). Pcc infection of the seeds amplified the content of unsaturated FAs. Nanopriming of the seeds with Se/AG NC had an obvious influence on the seedling FA profile. Treatment of soybean seeds infected with Pcc using Se/AG NC caused weakening of the detrimental effects of the pathogen, while giving the possibility to maintain soybean seedlings’ FA profile at the control level. Transcript levels of the GmFAD8-2 gene encoding the membrane-bound omega-3 FA desaturase (FAD) were elevated for soybean seedlings after both Pcc and Se/AG NC seed treatment processes. The FA double-bond index (DBI) grew under the influence of seed infection and dropped under other treatments. Nanopriming of the seeds with Se/AG NC effectively reduced stress in Pcc-infected plants, as evidenced by analysis of the abscisic acid (ABA) content. Variations in the membrane FA composition under nanopriming with Se/AG NC may be one of the forms of its phytoprotective effect. Full article

Epidermal lipid homeostasis is crucial for skin barrier integrity. This study investigated the effects of an aqueous extract from Beta vulgaris subsp. vulgaris Beetroot Group (BvE) on stress responses and lipid metabolism in HaCaT keratinocytes. BvE, obtained from leaves grown in SETIS^® bioreactors as a standardized biomass source, was chemically characterized by ¹H NMR and ¹³C NMR. HaCaT cells were treated with BvE (1 µg/mL), H₂O₂, or palmitic/oleic acids (PA/OA) to evaluate its protective effects against oxidative damage and lipotoxic stress. Under these conditions, BvE exhibited a distinctive dual action as a reactive oxygen species (ROS) scavenger and triacylglycerol (TAG)-lowering agent. On the one hand, BvE was associated with decreased intracellular ROS levels and changes in NRF2 protein expression, suggesting involvement of redox-regulatory pathways. On the other hand, it was associated with attenuation of lipotoxicity, as evidenced by reduced lipid droplet (LD) formation and decreased expression of DGAT1 and PLIN2. Furthermore, these effects were accompanied by a reduction in Unfolded Protein Response (UPR) markers, modulation of AMPK-associated signaling, attenuation of mitochondrial disfunction, and decreased p53 phosphorylation, findings collectively consistent with a coordinated cytoprotective response. In conclusion, BvE shows potential to protect keratinocytes against lipotoxicity and oxidative stress through mechanisms that may involve both chemical and biological antioxidant activity and metabolic reprogramming, supporting its further investigation for dermatological applications. Full article

Palmitic acid (PA), the most abundant saturated fatty acid in the human body, is implicated in lipotoxicity under hyperlipidemic conditions, with potential consequences for bone metabolism. To investigate its impact on developing bone tissue, this study used an ex vivo organotypic embryonic chick femur model, exposing femora to control (0 µM), low (50 µM), and high (200 µM) PA concentrations. A multimodal approach, integrating microtomographic, histochemical, ultrastructural, and gene expression analyses, was used to assess tissue architecture, matrix composition, mineralization, and molecular adaptations. PA exposure significantly reduced longitudinal femoral growth, as evidenced by decreased femoral length and tissue volume. Gene expression analysis revealed reduced expression of selected osteogenic differentiation-related markers, including RUNX2, BMP2, and SPP1. However, COL1A2 expression was upregulated, correlating with increased collagenous matrix deposition and enhanced mineralization in PA-treated groups. Alcian blue staining further suggested reduced proteoglycan-rich cartilage matrix, particularly at 200 µM PA. Additionally, PA modulated the expression of both pro-inflammatory and anti-inflammatory mediators, along with increased autophagy-associated responses, as suggested by the upregulation of autophagy-related genes and the presence of autophagosomes and autolysosomes. These findings indicate that PA does not simply exert a deleterious effect on bone tissue but rather redirects the developmental trajectory of the organotypic femur by reducing longitudinal growth while promoting collagen-rich matrix maturation and mineral compaction. This response may involve altered cartilage-associated endochondral processes, fatty-acid-driven metabolic adaptation, osteoblast/osteocyte maturation, and autophagy-associated matrix processing under lipid-enriched conditions. Full article

Background/Objectives: Palmitic acid (PA), the most abundant saturated fatty acid in circulation, is elevated in obese individuals and has been implicated in promoting inflammation. However, its effects on inflammatory cytokine production in microglial cells and the involvement of cell surface receptors remain poorly characterized. Methods: In this study, we treated BV2 murine microglial cells with 200 µM PA or bovine serum albumin (BSA) control for 24 h and assessed IL-1β expression using semi-quantitative RT-PCR and/or ELISA. The roles of toll-like receptor (TLR)-2, TLR-4, G-protein-coupled receptor (GPR) 40, and GPR120 were investigated using siRNA knockdown and/or pharmacological inhibition. Results: Our studies found that PA treatment significantly increased IL-1β production as well as the mRNA expression of TLR-2, TLR-4, GPR40, and GPR120 compared to BSA controls. IL-1β expression correlated positively with TLR-2, TLR-4, and GPR40 levels. RNAi silencing of TLR-2, TLR-4, or GPR40 substantially diminished IL-1β expression in cells exposed to both BSA and PA. In contrast, neither RNAi silencing nor pharmacological inhibition of GPR120 suppressed IL-1β expression, suggesting that GPR120 may not mediate PA-induced inflammation. Conclusions: Our studies suggest that PA-induced production of IL-1β may be mediated via TLR-2, TLR-4, and GPR40, and that these cell surface receptors may serve as important molecular links between saturated fatty acids (SFAs) and neuroinflammation. Full article

This study evaluated the use of HDES for omega-3 recovery from by-products of Octopus maya, an endemic species of the Yucatán Peninsula, Mexico. A 2 × 3 × 2 factorial design was applied to assess the effect of: (1) the hydrogen bond acceptor (HBA, menthol or eucalyptol) of hydrophobic deep eutectic solvents (HDES) with oleic acid as the hydrogen bond donor; (2) the molar ratio (MR) (1:1, 1:2, or 2:1); and (3) ultrasound-assisted extraction time (ET) (30 or 60 min) in omega-3 equivalents (EO3, mg/mL), determined by UV–Vis spectrophotometry and viscosity characterization to the Octopus maya extracted samples (n = 2), reported as $\overline{x}$ ± SD. The effects of the factors studied were analyzed by a DOE methodology with Minitab^® (version 18). Samples with the highest omega-3 were selected and their composition was confirmed by FTIR, Raman spectroscopy and gas chromatography. Eucalyptol at a molar ratio of 1:2 and an extraction time of 30 min yielded the highest OE3 (0.70 mg/mL). The statistical analysis revealed that the extraction of omega-3 determined by UV–Vis spectrophotometry was significantly influenced by the triple interaction of HBA × MR × ET (p < 0.05), indicating that extraction performance depends on the combined effect of solvent composition and processing conditions. All extracts showed Newtonian behavior with viscosities between 0.011 and 0.036 Pa·s, with eucalyptol formulations presenting the lowest values (0.011–0.023 Pa·s). Fatty acid profile allowed to quantify C16:0; C18:0; C18:1 n-9; C18:2 n-6; and C18:3 n-3, palmitic, stearic, oleic, linoleic and linolenic fatty acids, respectively, showing greater affinity for polyunsaturated fatty acids, mainly omega-6 (23.45–27.91%), and lower affinity for saturated fatty acids such as palmitic and stearic acids, indicating HDES as a sustainable alternative for selective extractions. Full article

With the rising prevalence of feline kidney diseases, effective preventive and therapeutic strategies are urgently needed. This study evaluated the effects of Cybister chinensis extracts (CCME) and Periplaneta americana residue extracts (PAE) on inflammation-associated, oxidative stress-related, and fibrosis-related responses in Crandell-Rees Feline Kidney (CRFK) cells. Using MTT assays, flow cytometry, and qPCR, we assessed cytoprotection in models of lipopolysaccharide (LPS)-, hydrogen peroxide (H₂O₂)-, and palmitic acid (PA)-induced injury. Preliminary HPLC fingerprint analysis of three batches of a combined extract from Periplaneta americana residues and Cybister chinensis Motschulsky (CPCE) revealed similar chromatographic profiles, indicating good batch-to-batch consistency. Within non-cytotoxic ranges, CPCE increased cell viability and reduced apoptosis in injured CRFK cells. Anti-inflammatory effects were evidenced by significant downregulation of TNF-α and IL-6 mRNA. Potential antioxidant-related effects were suggested by decreased expression of oxidative stress–responsive genes SOD1, CAT, and GSTP1. In the PA model, anti-fibrotic potential was supported by reduced TGFB1 expression, accompanied by improvements in inflammatory and oxidative stress markers, and by decreased levels of fibrosis-associated markers α-SMA, COL I, and HCB III. These findings suggest that CPCE exerts cytoprotective effects in vitro, potentially through modulation of inflammation, oxidative stress, and fibrosis. Full article

Seeds of Paeonia lactiflora Pall. ‘Hangshao’ contain over 20% oil, of which more than 90% are unsaturated fatty acids, showing its high potential as an oil crop. Triacylglycerol (TAG) is the main storage form of fatty acids, and diacylglycerol acyltransferase 2 (DGAT2) is a key enzyme in TAG biosynthesis. In this study, the full-length cDNA of PlDGAT2 (326 amino acids) was cloned. Subcellular localization assays further indicated that it localized in the endoplasmic reticulum. Functional verification showed that silencing PlDGAT2 in herbaceous peony decreased the level of total fatty acids, palmitic acid (C16:0, PA) and α-linolenic acid (C18:3, ALA), but increased linoleic acid (C18:2, LA) in leaves. Overexpressing PlDGAT2 in tobacco elevated the content of total fatty acids, PA, and ALA in seeds, while also enlarging the seed sizes, but it reduced the LA content in tobacco seeds. This study suggests that PlDGAT2 contributes to the accumulation of ALA and total fatty acids, offering a potential gene target for improving the oil quality of herbaceous peony seeds. Full article

This research aimed to systematically investigate the regulatory effects of six key fatty acids and rationally designed a functional fatty acid component (FFAC) to alleviate palmitic acid (PA)-induced glycolipid metabolism disorders and insulin resistance (IR) in HepG2 cells and Western diet-induced IR in the C57BL/6 mice model. In vitro experiments showed that saturated fatty acids such as PA and stearic acid (SA) induced concentration-dependent cytotoxicity and IR in HepG2 cells, while unsaturated fatty acids, including palmitoleic acid (POA), oleic acid (OA), linoleic acid (LA), and α-linolenic acid (ALA), enhanced cell viability and exerted protective effects. Based on the principle of balanced fatty acid ratio and the obtained cell experimental results, FFAC was designed as PA:SA:POA:OA:LA:ALA = 4:1:1:4:4:1 and formulated using dietary oils. In vivo, a 13-week dietary intervention revealed that FFAC substitution mitigated Western diet-induced weight gain, systemic IR, serum lipid disorders, and hepatic steatosis in mice. Mechanistically, FFAC restored the IRS1/PI3K/Akt/GSK3β insulin signaling pathway in HepG2 cells and reshaped gut microbiota by enriching beneficial genera such as Akkermansia. These findings demonstrated that FFAC effectively alleviates diet-induced metabolic disorders through multiple pathways, highlighting the potential of rationally designed dietary fatty acid compositions in managing metabolic disorders. Full article

Biodiesel is a biofuel commonly produced through transesterification, also known as alcoholysis. In this process, triglycerides react with short-chain alcohols (alkyl–OH), producing a mixture of fatty acid esters and glycerol. These esters and glycerol are only partially miscible, leading to the formation of two liquid phases during product separation. Therefore, it is important to experimentally determine liquid–liquid (LLE) and/or vapor–liquid–liquid equilibrium (VLLE) data to better understand the transesterification process and to support improvements in reaction rate, selectivity, reactor and mixture simulation, optimization, and separation processes. This work aimed to experimentally measure and thermodynamically model the LLE and VLLE of alkyl palmitate + alkyl–OH + glycerol systems at 101.3 kPa. For the LLE at 318.15 K, the binodal curve was determined, and tie-line compositions were measured in a jacketed equilibrium cell. These data were subjected to quality tests and used to calculate separation factors. For the VLLE, calibration curves were constructed, and experimental data were obtained in a modified Othmer ebulliometer and subsequently tested for consistency. Thermodynamic modeling was performed using γ–γ (LLE) and γ–γ–φ (VLLE) approaches with the Non-Random Two-Liquid (NRTL) activity coefficient model. The experimental and modeling results were analyzed using phase diagrams (triangular and 3D prism representations) and showed that it is possible to clearly separate the palmitate-rich and glycerol-rich liquid phases. In the VLLE, it was observed that the alkyl–OH is essentially pure in the vapor phase. For both types of equilibria, deviations in liquid-phase compositions (LLE), bubble temperatures, and vapor-phase compositions were below 2.0%, indicating that the NRTL model is capable of accurately describing the phase behavior of these systems. The phase equilibria of the methyl/ethyl palmitate–methanol/ethanol–glycerol system were studied using molecular dynamics (MD). The analyses based on the radial distribution function (RDF), spatial distribution function (SDF) and interaction energies showed that methanol and ethanol interact more strongly with glycerol than with palmitates. As a result, the glycerol-rich phase contains more methanol or ethanol, which can significantly reduce costs in the biodiesel purification step. Full article

While the adverse health effects of bisphenol A (BPA) or high-fat diet (HFD) exposure alone have been relatively well documented, the mechanisms underlying their combined impact on insulin resistance and type 2 diabetes remain poorly understood. In this study, we observed the effects of 90 days of treatment with BPA and an HFD on insulin resistance in mouse gastrocnemius muscle, as well as the expression of signaling molecules and proteins potentially associated with glucose transporter type 4 (GLUT4) translocation. Additionally, C2C12 myotubes were co-treated with BPA and palmitic acid (PA) to observe the effects on insulin signaling molecules, GLUT4 translocation, and insulin resistance. Specifically, in vitro cellular experiments further demonstrated that BPA and PA inhibited GLUT4 translocation from the nucleus to the cell membrane. Taken together, co-exposure to BPA and an HFD (or PA) treatment significantly altered the expression of insulin signaling molecules in both gastrocnemius muscle and C2C12 cells, suggesting a potential link to their impacts on insulin resistance and GLUT4 translocation. Full article