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Cell Cycle (Georgetown, Tex.) May 2022Obesity is associated with elevated levels of free fatty acids (FFAs). Excessive saturated fatty acids (SFAs) exhibit significant deleterious cytotoxic effects in many...
Obesity is associated with elevated levels of free fatty acids (FFAs). Excessive saturated fatty acids (SFAs) exhibit significant deleterious cytotoxic effects in many types of cells. However, the effects of palmitic acid (PA), the most common circulating SFA, on cell cycle progression in neuronal cells have not been well-examined. The aim of this study was to examine whether PA affects the proliferation and cell cycle progression in mouse neuroblastoma Neuro-2a (N2a) cells. Our studies found that 200 µM PA significantly decreased DNA synthesis and mitotic index in N2a cells as early as 4 h following treatment. 24 h treatment with 200 µM PA significantly decreased the percentage of diploid (2 N) cells while dramatically increasing the percentage of tetraploid (4 N) cells as compared to the BSA control. Moreover, our studies found that 24 h treatment with 200 µM PA increased the percentage of binucleate cells as compared to the BSA control. Our studies also found that unsaturated fatty acids (UFAs), including linoleic acid, oleic acid, α-linolenic acid, and docosahexaenoic acid, were able to abolish PA-induced decrease of 2 N cells, increase of 4 N cells, and accumulation of binucleate cells. Taken together, these results suggest that PA may affect multiple aspects of the cell cycle progression in N2a cells, including decreased DNA synthesis, G2/M arrest, and cytokinetic failure, which could be abolished by UFAs. 4-PBA, 4-Phenylbutyric Acid; ALA, α-linolenic acid; BrdU, 5-bromo-2'-deoxyuridine; DAPI, 4',6-diamidino-2-phenylindole; ER, endoplasmic reticulum; FFA, free fatty acids; FITC, fluorescein isothiocyanate; LA, linoleic acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; N2a, Neuro-2a; NAC, N-acetyl cysteine; OA, oleic acid; PA, palmitic acid; pHH3, Phosphorylation of histone H3; PI, propidium iodide; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; UFA, unsaturated fatty acids.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cytokinesis; DNA; Fatty Acids; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; G2 Phase Cell Cycle Checkpoints; Linoleic Acids; Mice; Oleic Acids; Palmitic Acid; alpha-Linolenic Acid
PubMed: 35171079
DOI: 10.1080/15384101.2022.2040769 -
Scientific Reports Mar 2021Saturated fatty acids such as palmitic acid promote inflammation and insulin resistance in peripheral tissues, contrasting with the protective action of polyunsaturated...
Saturated fatty acids such as palmitic acid promote inflammation and insulin resistance in peripheral tissues, contrasting with the protective action of polyunsaturated fatty acids such docosahexaenoic acid. Palmitic acid effects have been in part attributed to its potential action through Toll-like receptor 4. Beside, resistin, an adipokine, also promotes inflammation and insulin resistance via TLR4. In the brain, palmitic acid and resistin trigger neuroinflammation and insulin resistance, but their link at the neuronal level is unknown. Using human SH-SY5Yneuroblastoma cell line we show that palmitic acid treatment impaired insulin-dependent Akt and Erk phosphorylation whereas DHA preserved insulin action. Palmitic acid up-regulated TLR4 as well as pro-inflammatory cytokines IL6 and TNFα contrasting with DHA effect. Similarly to palmitic acid, resistin treatment induced the up-regulation of IL6 and TNFα as well as NFκB activation. Importantly, palmitic acid potentiated the resistin-dependent NFkB activation whereas DHA abolished it. The recruitment of TLR4 to membrane lipid rafts was increased by palmitic acid treatment; this is concomitant with the augmentation of resistin-induced TLR4/MYD88/TIRAP complex formation mandatory for TLR4 signaling. In conclusion, palmitic acid increased TLR4 expression promoting resistin signaling through TLR4 up-regulation and its recruitment to membrane lipid rafts.
Topics: Cell Line, Tumor; Humans; Inflammation; Insulin Resistance; Neoplasm Proteins; Neuroblastoma; Palmitic Acid; Resistin
PubMed: 33686181
DOI: 10.1038/s41598-021-85018-7 -
International Journal of Biological... Apr 2022The starch-palmitic acid complex nanoparticles were prepared by Cyperus esculentus starch with enzymatic hydrolysis for different times and then complexed with palmitic...
The starch-palmitic acid complex nanoparticles were prepared by Cyperus esculentus starch with enzymatic hydrolysis for different times and then complexed with palmitic acid. The FACE and C CP/MAS NMR analysis showed that there were more amylose molecules formed and complexed with palmitic acid when starch was treated by enzymatic hydrolysis for 4 h. With the enzymatic hydrolysis time increasing from 0 h to 4 h, the mean size of starch-palmitic acid complex nanoparticles increased from 500 ± 38.83 nm to 567.2 ± 22.32 nm, the size distribution became more uniform, and the crystallinity increased from 14.99% to 47.72%. The starch-palmitic acid complex nanoparticles could be used as a kind of stabilizers to stabilize Pickering emulsions. Rheological properties and storage stability of Pickering emulsions indicted that starch-palmitic acid complex nanoparticles can better stabilize. The starch-palmitic acid complex nanoparticles could be used as stabilizer of Pickering emulsion and encapsulation of bioactive compounds.
Topics: Emulsions; Nanoparticles; Palmitic Acid; Particle Size; Starch
PubMed: 35134453
DOI: 10.1016/j.ijbiomac.2022.01.170 -
Biochemical and Biophysical Research... Jul 2022Hepatic lipid accumulation is an initiation factor in fatty liver disease, and promoting a reduction in hepatic lipid accumulation is an important treatment strategy....
Hepatic lipid accumulation is an initiation factor in fatty liver disease, and promoting a reduction in hepatic lipid accumulation is an important treatment strategy. DEAD box RNA helicase 17 (DDX17) is a member of the DEAD-box family and a molecular chaperone. Previous studies have demonstrated that DDX17 is a transcriptional coregulator of tumorigenesis, inflammation, and macrophage cholesterol efflux. The liver is the main site for lipid metabolism, and metabolic (dysfunction)-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases. However, the impact of DDX17 on hepatic lipid accumulation has not been verified. In this study, we found, for the first time, that oleic acid/palmitic acid (OA/PA)-induced lipid accumulation was largely abrogated by DDX17 overexpression in both HepG2 (a human hepatocellular carcinoma line) and Hep1-6 (a murine hepatocellular carcinoma line) cells, and this effect was due to a marked reduction in cellular triglyceride (TG) content. Moreover, the overexpression of DDX17 was accompanied by a significant decrease in the expression of genes involved in de novo fatty acid synthesis (FAS, ACC, and SCD-1) in both HepG2 and Hep1-6 cells. In conclusion, DDX17 protected against OA/PA-induced lipid accumulation in hepatocytes through de novo lipogenesis inhibition.
Topics: Animals; Carcinoma, Hepatocellular; DEAD-box RNA Helicases; Hep G2 Cells; Hepatocytes; Humans; Lipid Metabolism; Lipogenesis; Liver; Liver Neoplasms; Mice; Non-alcoholic Fatty Liver Disease; Oleic Acid; Palmitic Acid
PubMed: 35533489
DOI: 10.1016/j.bbrc.2022.04.129 -
Cell Metabolism Jan 2022Diet can influence tumor aggressiveness. Recently in Nature, a study by Pascual et al. provided evidence that dietary palmitic acid induces an epigenetic memory by...
Diet can influence tumor aggressiveness. Recently in Nature, a study by Pascual et al. provided evidence that dietary palmitic acid induces an epigenetic memory by modulating particular histone methylation marks in cancer cells. This allows cancer cells to activate extracellular matrix secretion from Schwann cells of the tumor microenvironment, which ultimately potentiates metastasis initiation.
Topics: Epigenomics; Humans; Methylation; Neoplasms; Palmitic Acid; Tumor Microenvironment
PubMed: 34986339
DOI: 10.1016/j.cmet.2021.12.015 -
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 -
Nutrients Aug 2023Metabolic endotoxemia (ME) is characterized by a 2-3-fold increase in blood endotoxin levels and low-grade systemic inflammation without apparent infection. ME is...
Metabolic endotoxemia (ME) is characterized by a 2-3-fold increase in blood endotoxin levels and low-grade systemic inflammation without apparent infection. ME is usually accompanied by metabolic syndrome, characterized by central obesity and hyperlipidemia. According to numerous studies, ME may lead to functional brain disorders, including cognitive decline, depression, and dementia. In the current in vitro study, we aimed to determine the direct and indirect impact of endotoxin (LPS) and palmitic acid (PA), representing saturated fatty acids, on the inflammatory and oxidative stress response in the human microglial HMC3 cells unstimulated and stimulated with IFNγ. The study's results revealed that direct HMC3 cell exposition to endotoxin and PA increased inflammatory response measured as levels of IL-6 and MCP-1 released into the medium and PGE2 levels in cell lysates. Moreover, direct HMC3 cell treatment with PA and LPS induced oxidative stress, i.e., ROS and COX-2 production and lipid peroxidation. On the contrary, an indirect effect of LPS and PA on microglial cells, assessed as the impact of macrophage metabolites, was much lower regarding the inflammatory response, although still associated with oxidative stress. Interestingly, IFNγ had a protective effect on microglial cells, reducing the production of pro-inflammatory mediators and oxidative stress in HMC3 cells treated directly and indirectly with LPS and PA.
Topics: Humans; Microglia; Palmitic Acid; Endotoxemia; Lipopolysaccharides; Inflammation
PubMed: 37571401
DOI: 10.3390/nu15153463 -
Veterinary Medicine and Science Nov 2021Restricted placental angiogenesis is an important cause of intrauterine growth retardation in piglets. During pregnancy, sow obesity can result in an increase in...
Restricted placental angiogenesis is an important cause of intrauterine growth retardation in piglets. During pregnancy, sow obesity can result in an increase in placental lipid deposition, subsequently inhibiting placental angiogenesis and fetal development. However, the effect of different types of fatty acids on placental angiogenesis is still unclear. Trophoblast cells and vascular endothelial cells constitute two important types of placental tissue. In this study, we used palmitic acid (C16:0) and eicosapentaenoic acid (C20:5, n-3), respectively, to treat porcine trophectoderm cells (pTr2) and porcine iliac artery endothelial cells (PIEC) to study the effects of saturated fatty acids and n-3 polyunsaturated fatty acids (PUFAs) on placental angiogenesis in vitro. We found that C16:0 caused significant cytotoxicity in pTr2 and PIEC (p < 0.01) and inhibited the proliferation and migration of PIEC (p < 0.01), whereas C20:5 treatment exhibited very low cytotoxicity and minimal inhibition of cellular proliferation. Meanwhile, a low concentration of C16:0 had no effect on the tube formation in PIEC, whereas C20:5 significantly promoted tube formation of PIEC (p < 0.01). These results suggested that saturated fatty acids and n-3 PUFAs had different effects on placental angiogenesis. As essential functional fatty acid, n-3 PUFA might be effective measure in alleviating the placental lipotoxicity caused by sow obesity during pregnancy.
Topics: Animals; Eicosapentaenoic Acid; Endothelial Cells; Fatty Acids, Omega-3; Female; Palmitic Acid; Placenta; Pregnancy; Swine
PubMed: 34547178
DOI: 10.1002/vms3.577 -
Food Chemistry May 2022The physical properties of butter are impacted by the fatty acid and triacylglycerol composition of the milkfat. Increased butter hardness and melting temperature...
The physical properties of butter are impacted by the fatty acid and triacylglycerol composition of the milkfat. Increased butter hardness and melting temperature results in decreased consumer satisfaction since these affect the culinary performance and spreadability. During the winter of 2021, consumers reported anecdotal evidence of an increase in butter hardness, leading to news reports blaming the increased hardness on palm oil-based supplementation of cows' feed. Commercial butter samples were collected from across Canada to test the correlation between fatty acid and triacylglycerol composition, and hardness. We determined that palmitic acid (r = 0.74) and dipalmitoyloleate (r = 0.72) were significantly and positively correlated to commercial butter hardness (P < 0.01). However, due to restricted access to existing historical data on the chemical composition of milk fat and hardness of butter, it was not possible to compare the firmness of butter in 2021 with butter produced in the past.
Topics: Animals; Butter; Cattle; Fatty Acids; Female; Milk; Palmitic Acid; Triglycerides
PubMed: 34995963
DOI: 10.1016/j.foodchem.2021.131991 -
Frontiers in Immunology 2022Weight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing diabetes and cardiovascular disease....
INTRODUCTION
Weight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing diabetes and cardiovascular disease. We previously reported that male mice retain obesity-associated immunological changes even after weight loss, suggesting that immune cells may remember the state of obesity. Therefore, we hypothesized that cycles of weight gain and loss, otherwise known as weight cycling, can induce innate memory in adipose macrophages.
METHODS
Bone marrow derived macrophages were primed with palmitic acid or adipose tissue conditioned media in a culture model of innate immune memory. Mice also put on low fat or high fat diets over 14-27 weeks to induce weight gain, weight loss, and weight cycling.
RESULTS
Priming cells with palmitic acid or adipose tissue conditioned media from obese mice increased maximal glycolysis and oxidative phosphorylation and increased LPS-induced TNFα and IL-6 production. Palmitic acid effects were dependent on TLR4 and impaired by methyltransferase inhibition and AMPK activation. While weight loss improved glucose tolerance in mice, adipose macrophages were primed for greater activation to subsequent stimulation by LPS as measured by cytokine production. In the model of weight cycling, adipose macrophages had elevated metabolism and secreted higher levels of basal TNFα, suggesting that weight loss can also prime macrophages for heighted activation to weight regain.
DISCUSSION
Together, these data suggest that weight loss following obesity can prime adipose macrophages for enhanced inflammation upon weight regain. This innate immune memory response may contribute to worsened glucose tolerance following weight cycling.
Topics: Male; Mice; Animals; Tumor Necrosis Factor-alpha; Weight Cycling; Trained Immunity; Palmitic Acid; Culture Media, Conditioned; Lipopolysaccharides; Insulin Resistance; Adipose Tissue; Obesity; Macrophages; Weight Gain; Diabetes Mellitus; Weight Loss; Glucose
PubMed: 36713396
DOI: 10.3389/fimmu.2022.984859