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International Journal of Molecular... Sep 2023Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipids within hepatocytes, which compromises liver functionality following...
Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipids within hepatocytes, which compromises liver functionality following mitochondrial dysfunction and increased production of reactive oxygen species (ROS). Lipoic acid is one of the prosthetic groups of the pyruvate dehydrogenase complex also known for its ability to confer protection from oxidative damage because of its antioxidant properties. In this study, we aimed to investigate the effects of lipoic acid on lipotoxicity and mitochondrial dynamics in an in vitro model of liver steatosis. HepG2 cells were treated with palmitic acid and oleic acid (1:2) to induce steatosis, without and with 1 and 5 µM lipoic acid. Following treatments, cell proliferation and lipid droplets accumulation were evaluated. Mitochondrial functions were assessed through the evaluation of membrane potential, MitoTracker Red staining, expression of genes of the mitochondrial quality control, and analysis of energy metabolism by HPLC and Seahorse. We showed that lipoic acid treatment restored membrane potential to values comparable to control cells, as well as protected cells from mitochondrial fragmentation following PA:OA treatment. Furthermore, our data showed that lipoic acid was able to determine an increase in the expression of mitochondrial fusion genes and a decrease in mitochondrial fission genes, as well as to restore the bioenergetics of cells after treatment with palmitic acid and oleic acid. In conclusion, our data suggest that lipoic acid reduces lipotoxicity and improves mitochondrial functions in an in vitro model of steatosis, thus providing a potentially valuable pharmacological tool for NAFLD treatment.
Topics: Humans; Thioctic Acid; Non-alcoholic Fatty Liver Disease; Palmitic Acid; Oleic Acid; Mitochondria; Hepatocytes; Oxidative Stress; Energy Metabolism; Liver
PubMed: 37833939
DOI: 10.3390/ijms241914491 -
Journal of Dairy Science Oct 2020Saturated fatty acid supplements commonly fed to dairy cows differ in their fatty acid (FA) profile. Some supplements with very high enrichments of palmitic acid (PA) or...
Saturated fatty acid supplements commonly fed to dairy cows differ in their fatty acid (FA) profile. Some supplements with very high enrichments of palmitic acid (PA) or stearic acid (SA) have been reported to have low total-tract digestibility. Saturated FA have the potential to form crystalline structures at high purity that may affect digestibility. Differential scanning calorimetry (DSC) is a thermal technique commonly used in materials science to measure the change in heat flow as energy is absorbed or released from a sample during heating, and it was used to characterize a series of experimental and commercial fat supplements. Our hypothesis was that products with very high enrichment of either PA or SA would differ in thermal characteristics compared with those that include moderate levels of a second FA because of the formation of secondary crystalline structures, which may contribute to decreased digestibility. First, replicated runs demonstrated low variation in melting temperature (MT) and enthalpy (coefficient of variation <4%). The effect of physical form was evaluated by comparing an initial thermal cycle to a second, successive thermal cycle after samples had resolidified in the test pan. Melting temperature was slightly increased by 1.3°C by the second cycle compared with the first, but there was no change in enthalpy. Next, supplements with 98% SA, 98% PA, and an SA/PA (44%/55%) blend with undetectable levels of unsaturated FA were compared. Melting temperature of the SA/PA mixture was 61.2°C and similar to the expected MT of PA (62.9°C). However, the MT of the high-purity SA and PA were increased to 73.7°C and 67.8°C, respectively, and enthalpy increased by 12.5% compared with the SA/PA blend. An FA stock highly enriched in SA (>98%) had the highest MT, and one moderately enriched in PA (∼85%) that contained 10.1% unsaturated FA had the lowest enthalpy value of all FA supplements and experimental stocks that were characterized. Differential scanning calorimetry may be useful to screen and design supplements with improved physical properties that may be associated with digestibility.
Topics: Animal Feed; Animals; Calorimetry, Differential Scanning; Cattle; Diet; Dietary Supplements; Digestion; Fatty Acids; Female; Lactation; Milk; Palmitic Acid; Stearic Acids; Thermodynamics
PubMed: 32747096
DOI: 10.3168/jds.2019-18131 -
Neurotoxicity Research Oct 2020Lipotoxicity is a pathological condition resulting from the excessive accumulation of fatty acids, like palmitic acid (PA), within the cell. This pathological phenomenon...
Lipotoxicity is a pathological condition resulting from the excessive accumulation of fatty acids, like palmitic acid (PA), within the cell. This pathological phenomenon induces deleterious metabolic changes in cells and is associated with neurodegenerative diseases, dyslipidemia, and obesity. Recent evidence has demonstrated that tibolone, a synthetic steroid, protects cellular damage through various mechanisms; but its underlying actions upon lipotoxic damage are unknown. In this study, we assessed the effects of tibolone administration on normal human astrocytes subject to supraphysiological levels of palmitic acid as a model to induce cytotoxicity. Our results demonstrated that tibolone attenuated lipotoxic damage of PA in normal human astrocytes by reducing PI uptake in 53%, prevented cardiolipin loss by 17%, reduced fragmented/condensed nuclei by 50.81% and attenuated the production of superoxide ions by around 20%. In conclusion, these data suggest that protective effects of tibolone against lipotoxicity may be mediated, in part, through modulation of the different cellular mechanisms of astrocytes.
Topics: Astrocytes; Cell Line; Cell Survival; Humans; Membrane Potential, Mitochondrial; Neurons; Norpregnenes; Palmitic Acid
PubMed: 32638213
DOI: 10.1007/s12640-020-00247-4 -
Food and Chemical Toxicology : An... May 2014In this study, we identified the toxic mechanism following the accumulation of palmitic acid (PA), a saturated fatty acid, in human Chang liver cells. After PA exposure...
In this study, we identified the toxic mechanism following the accumulation of palmitic acid (PA), a saturated fatty acid, in human Chang liver cells. After PA exposure for 24 h, the mitochondria and the endoplasmic reticulum (ER) became dilated, and lipid droplets and organelles were observed within autophagosomes. Cell viability decreased with an ATP reduction and the G2/M phase arrest. The expression of SOD-2, but not of SOD-1, markedly increased after PA exposure, which also elevated the number of cells generating ROS. PA enhanced the levels of proteins related to apoptosis, necroptosis, autophagy, and ER stress. Moreover, the inhibition of caspases, p53, necroptosis, or ER stress substantially rescued PA-induced cytotoxicity and, similarly, the inhibition of caspases and ER stress counteracted PA-induced changes in the cell cycle. Conversely, the inhibition of necroptosis and p53 signaling accelerated the changes in the cell cycle triggered by PA exposure. Blocking autophagy exacerbated PA-induced cytotoxicity and alterations in the cell cycle and caused disappearance of cellular components. These results suggest that PA induces apoptosis accompanied by autophagy through mitochondrial dysfunction and ER stress, which are triggered by oxidative stress in Chang liver cells and that blocking autophagy accelerates cell damage following PA exposure.
Topics: Cells, Cultured; Humans; Microscopy, Electron, Transmission; Palmitic Acid; Reactive Oxygen Species
PubMed: 24486139
DOI: 10.1016/j.fct.2014.01.027 -
Molecules (Basel, Switzerland) Jun 2021Tripalmitin-(PPP, 81.2%), 1,3-dipalmitoyl-2-oleoylglycerol-(POP, 64.4%), 1,2-dipalmitoyl-3-oleoylglycerol-(PPO, 86.5%), and 1,3-dioleoyl-2-palmitoylglycerol-(OPO,...
Tripalmitin-(PPP, 81.2%), 1,3-dipalmitoyl-2-oleoylglycerol-(POP, 64.4%), 1,2-dipalmitoyl-3-oleoylglycerol-(PPO, 86.5%), and 1,3-dioleoyl-2-palmitoylglycerol-(OPO, 50.2%)-rich lipids with different regiospecific positions of palmitic acid (P) were synthesized via acetone fractionation and lipase-catalyzed acidolysis, and their physicochemical and hydrolytic characteristics were compared. Triacylglycerols (TAGs) with higher content of P, wherein P was at the -1 (or 3) position, had higher melting points, crystallization temperatures, and packing densities of fat crystals compared to those with a lower content of P, and with P at the -2 position. The in vitro digestion degree calculated as released fatty acid (FA) (%) at 30, 60, and 120 min was in the following order: OPO-rich > PPO-rich > POP-rich lipids. At 120 min, in vitro digestion of the OPO-rich lipid released 92.6% of fatty acids, resulting in the highest digestibility, while 89.7% and 87.2% of fatty acids were released from the OPO-rich and PPO-rich lipids, respectively. Over the digestion period, the TAG and monoacylglycerol (MAG) contents decreased, while the diacylglycerol (DAG) content initially increased and then decreased, and the 1,2-DAG content exceeded the 1,3-DAG content. Therefore, the content and stereospecific position of P attached to a specific TAG affected the physicochemical and in vitro digestion characteristics of the lipids.
Topics: Digestion; Lipase; Monoglycerides; Palmitic Acid; Triglycerides
PubMed: 34209258
DOI: 10.3390/molecules26134015 -
Molecules (Basel, Switzerland) Mar 2022Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. An elevated fatty acid plasma concentration leads to podocyte injury and DN progression. This...
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. An elevated fatty acid plasma concentration leads to podocyte injury and DN progression. This study aimed to identify and characterize cellular mechanisms of natural compounds that inhibit palmitic acid (PA)-induced human podocyte injury. By screening 355 natural compounds using a cell viability assay, 3-hydroxyterphenyllin (3-HT) and candidusin A (CDA), isolated from the marine-derived fungus PSU-AMF169, were found to protect against PA-induced podocyte injury, with half-maximal inhibitory concentrations (IC) of ~16 and ~18 µM, respectively. Flow cytometry revealed that 3-HT and CDA suppressed PA-induced podocyte apoptosis. Importantly, CDA significantly prevented PA-induced podocyte barrier impairment as determined by 70 kDa dextran flux. Reactive oxygen species (ROS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) direct scavenging assays indicated that both compounds exerted an anti-oxidative effect via direct free radical-scavenging activity. Moreover, 3-HT and CDA upregulated the anti-apoptotic Bcl2 protein. In conclusion, 3-HT and CDA represent fungus-derived bioactive compounds that have a novel protective effect on PA-induced human podocyte apoptosis via mechanisms involving free radical scavenging and Bcl2 upregulation.
Topics: Apoptosis; Diabetic Nephropathies; Fungi; Humans; Palmitic Acid; Podocytes; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Terphenyl Compounds
PubMed: 35408508
DOI: 10.3390/molecules27072109 -
Food Research International (Ottawa,... Jun 2024The oxidation and degradation of fats lead to a decrease in the nutritional value of food and pose safety concerns. Saturated fatty acids also hold a significant...
The oxidation and degradation of fats lead to a decrease in the nutritional value of food and pose safety concerns. Saturated fatty acids also hold a significant position in the field of lipid oxidation. In this study, the oxidation products of methyl palmitate were investigated by using gas chromatography mass spectrometry (GC-MS). Seven monohydroperoxides and 72 secondary oxidation products were detected. Combined with density functional theory (DFT) calculations, the formation mechanisms of oxidation products can be summarized into four stages. The initial stage involved the formation of monohydroperoxides and alkanes, followed by the subsequent stage involving methyl x-oxo(hydroxy)hexadecanoates. The third stage involved the formation of methyl ketones, carboxylic acids, and aldehydes, while the final stage involved lactones. Meanwhile, methyl ketones were the most abundant oxidation product, approximately 25 times more abundant than aldehydes; the calculated results agreed well with the experimental results. The establishment of a comprehensive thermal oxidation mechanism for palmitic acid provided a new foundation for future lipid oxidation analyses.
Topics: Oxidation-Reduction; Gas Chromatography-Mass Spectrometry; Hot Temperature; Aldehydes; Palmitates; Palmitic Acid; Ketones; Carboxylic Acids
PubMed: 38729730
DOI: 10.1016/j.foodres.2024.114372 -
The American Journal of Clinical... Aug 2019Direct comparisons between SFAs varying in chain length, specifically palmitic acid (16:0) and stearic acid (18:0), relative to the latter's metabolic product, oleic... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of diets enriched in stearic, oleic, and palmitic acids on inflammation, immune response, cardiometabolic risk factors, and fecal bile acid concentrations in mildly hypercholesterolemic postmenopausal women-randomized crossover trial.
BACKGROUND
Direct comparisons between SFAs varying in chain length, specifically palmitic acid (16:0) and stearic acid (18:0), relative to the latter's metabolic product, oleic acid (18:1), on cardiometabolic risk factors are limited.
OBJECTIVE
The aim of this study was to determine the relative comparability of diets enriched in palmitic acid, stearic acid, and oleic acid on inflammation and coagulation markers, T lymphocyte proliferation/ex-vivo cytokine secretion, plasma cardiometabolic risk factors, and fecal bile acid concentrations.
METHODS
Hypercholesterolemic postmenopausal women (n = 20, mean ± SD age 64 ± 7 y, BMI 26.4 ± 3.4 kg/m2, LDL cholesterol ≥ 2.8 mmol/L) were provided with each of 3 diets [55% energy (%E) carbohydrate, 15%E protein, 30%E fat, with ∼50% fat contributed by palmitic acid, stearic acid, or oleic acid in each diet; 5 wk/diet phase] using a randomized crossover design with 2-wk washouts between phases. Outcome measures were assessed at the end of each phase.
RESULTS
Fasting LDL-cholesterol and non-HDL-cholesterol concentrations were lower after the stearic acid and oleic acid diets than the palmitic acid diet (all P < 0.01). Fasting HDL-cholesterol concentrations were lower after the stearic acid diet than the palmitic acid and oleic acid diets (P < 0.01). The stearic acid diet resulted in lower lithocholic acid (P = 0.01) and total secondary bile acid (SBA) concentrations (P = 0.04) than the oleic acid diet. All other outcome measures were similar between diets. Lithocholic acid concentrations were positively correlated with fasting LDL-cholesterol concentrations (r = 0.33; P = 0.011). Total SBA, lithocholic acid, and deoxycholic acid concentrations were negatively correlated with fasting HDL cholesterol (r = -0.51 to -0.44; P < 0.01) concentrations and positively correlated with LDL cholesterol:HDL cholesterol (r = 0.37-0.54; P < 0.01) ratios.
CONCLUSIONS
Dietary stearic acid and oleic acid had similar effects on fasting LDL-cholesterol and non-HDL-cholesterol concentrations and more favorable ones than palmitic acid. Unlike oleic acid, the hypocholesterolemic effect of stearic acid may be mediated by inhibition of intestinal hydrophobic SBA synthesis. These findings add to the data suggesting there should be a reassessment of current SFA dietary guidance and Nutrient Facts panel labeling.This trial was registered at clinicaltrials.gov as NCT02145936.
Topics: Adult; Aged; Aged, 80 and over; Bile Acids and Salts; Cardiovascular Diseases; Cross-Over Studies; Feces; Female; Humans; Hypercholesterolemia; Inflammation; Middle Aged; Oleic Acid; Palmitic Acid; Postmenopause; Risk Factors; Stearic Acids
PubMed: 31179489
DOI: 10.1093/ajcn/nqz095 -
Journal of Oleo Science Jun 2018Most natural lipids contain a complex mixture of individual triacylglycerols (TAGs). An in-depth knowledge of the mixing behavior of TAGs is necessary for the rational... (Review)
Review
Most natural lipids contain a complex mixture of individual triacylglycerols (TAGs). An in-depth knowledge of the mixing behavior of TAGs is necessary for the rational design and engineering of food materials. The binary phase diagram of TAGs is a simplified model that can be explored to help foster an understanding of the phase behavior of complex fats and oils. This article reviews recent research on the binary phase behavior of saturated-unsaturated mixed-acid TAGs, with special emphasis on the stearicunsaturated and palmitic-unsaturated diacid TAGs. The occurrence of polymorphic forms and mutual solubility of TAG mixtures are strongly related to the glycerol conformation of the saturated-oleic diacid TAGs; it appears to be most influenced by the chain-length mismatch in saturated-elaidic diacid TAGs. In addition, the polymorphism of pure enantiomers and racemic mixture of chiral TAGs was also reviewed, while the effect of chirality on mixing behavior was discussed.
Topics: Fatty Acids, Unsaturated; Food; Oleic Acid; Oleic Acids; Palmitic Acid; Phase Transition; Stearic Acids; Triglycerides
PubMed: 29760333
DOI: 10.5650/jos.ess17263 -
Natural Product Research Mar 2024Obesity is a metabolic disorder with excessive body fat accumulation, increasing incidence of chronic metabolic diseases. Hypertrophic obesity is associated with local...
Obesity is a metabolic disorder with excessive body fat accumulation, increasing incidence of chronic metabolic diseases. Hypertrophic obesity is associated with local oxidative stress and inflammation. Herein, we evaluated the activity of micromolar concentrations of α-lipoic acid (ALA) on palmitic acid (PA)-exposed murine hypertrophic 3T3-L1 adipocytes, focussing on the main molecular pathways involved in adipogenesis, inflammation, and insulin resistance. ALA, starting from 1 µM, decreased adipocytes hypertrophy, reducing PA-triggered intracellular lipid accumulation, PPAR-γ levels, and FABP4 gene expression, and counteracted PA-induced intracellular ROS levels and NF-κB activation. ALA reverted PA-induced insulin resistance, restoring PI3K/Akt axis and inducing GLUT-1 and glucose uptake, showing insulin sensitizing properties since it increased their basal levels. In conclusion, this study supports the potential effects of low micromolar ALA against hypertrophy, inflammation, and insulin resistance in adipose tissue, suggesting its important role as pharmacological supplement in the prevention of conditions linked to obesity and metabolic syndrome.
Topics: Animals; Mice; Thioctic Acid; Palmitic Acid; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipocytes; Hypertrophy; Obesity; Inflammation
PubMed: 37129014
DOI: 10.1080/14786419.2023.2207137