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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 -
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 -
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 -
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 -
Biomolecules May 2024Epidemiological and clinical evidence have extensively documented the role of obesity in the development of endometrial cancer. However, the effect of fatty acids on...
Epidemiological and clinical evidence have extensively documented the role of obesity in the development of endometrial cancer. However, the effect of fatty acids on cell growth in endometrial cancer has not been widely studied. Here, we reported that palmitic acid significantly inhibited cell proliferation of endometrial cancer cells and primary cultures of endometrial cancer and reduced tumor growth in a transgenic mouse model of endometrial cancer, in parallel with increased cellular stress and apoptosis and decreased cellular adhesion and invasion. Inhibition of cellular stress by N-acetyl-L-cysteine effectively reversed the effects of palmitic acid on cell proliferation, apoptosis, and invasive capacity in endometrial cancer cells. Palmitic acid increased the intracellular formation of lipid droplets in a time- and dose-dependent manner. Depletion of lipid droplets by blocking DGAT1 and DGAT2 effectively increased the ability of palmitic acid to inhibit cell proliferation and induce cleaved caspase 3 activity. Collectively, this study provides new insight into the effect of palmitic acid on cell proliferation and invasion and the formation of lipid droplets that may have potential clinical relevance in the treatment of obesity-driven endometrial cancer.
Topics: Female; Palmitic Acid; Endometrial Neoplasms; Humans; Lipid Droplets; Animals; Cell Proliferation; Mice; Apoptosis; Cell Line, Tumor; Diacylglycerol O-Acyltransferase; Mice, Transgenic
PubMed: 38786008
DOI: 10.3390/biom14050601 -
Experimental Cell Research Aug 2023Lipotoxicity caused by excess free fatty acids, particularly saturated fatty acids (SFAs) such as palmitic acid (PA), is one of the most important pathogenesis of...
Lipotoxicity caused by excess free fatty acids, particularly saturated fatty acids (SFAs) such as palmitic acid (PA), is one of the most important pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, unsaturated fatty acids (UFAs), such as oleic acid (OA), are nontoxic and can combat SFA-induced toxicity through alleviation of cell apoptosis, endoplasmic reticulum stress (ER stress) and lipids metabolism disorder. However, whether OA is able to regulate autophagy is largely unknown. So, this study aims to investigate the mechanism underlying OA mediated modulation of autophagy in hepatocytes and mice with NAFLD. In vitro, human hepatoma cell line HepG2 cells, human normal liver cells L-02 and mouse normal liver cells AML12 were treated with palmitic acid (PA)/tunicamycin (TM) or/and OA for 48 h. In vivo, C57/BL6 mice were fed with high fat diet (HFD) to induce NAFLD. And the HFD was partial replaced by olive oil to observe the protective effects of olive oil. We demonstrated that PA/TM impaired cell viability and induced cellular apoptosis in HepG2 cells and L-02 cells. Moreover, PA/TM induced autophagy impairment by reducing the nuclear translocation of transcription factor EB (TFEB) and inhibiting the activity of CTSB. However, OA substantially alleviated PA/TM induced cellular apoptosis and autophagy dysfunction in hepatocytes. Additionally, restoring autophagy function is able to reduce ER stress. Similarly, HFD for 20 weeks successfully established NAFLD model in C57/BL6 mice, and significant autophagy impairment were observed in liver tissues. Noteworthily, 30% replacement of HFD with olive oil had profoundly reversed NAFLD. It significantly impoved steatosis, and reduced autophagy dysfunction, ER stress and apoptosis in liver tissue. Conclusively, these data demonstrated that OA is able to effectively impove autophagy dysfunction under the context of both PA and ER stress inducer induced lipotoxicity, and OA mediated regulation of lysosome dysfunction through TFEB plays an important role, suggesting that the regulation of ER stress-autophagy axis is a critical mechanism in OA driven protection in NAFLD.
Topics: Mice; Humans; Animals; Non-alcoholic Fatty Liver Disease; Oleic Acid; Olive Oil; Liver; Hepatocytes; Palmitic Acid; Autophagy; Endoplasmic Reticulum Stress; Diet, High-Fat
PubMed: 37253404
DOI: 10.1016/j.yexcr.2023.113655 -
Prostaglandins, Leukotrienes, and... Jun 2021Adipose tissue resident macrophages play an important role in the regulation of the inflammatory response. Monounsaturated fatty acids assist in the prevention of...
Adipose tissue resident macrophages play an important role in the regulation of the inflammatory response. Monounsaturated fatty acids assist in the prevention of cardiovascular diseases via an anti-inflammatory effect. However, the mechanisms by which monounsaturated fatty acids, such as palmitoleic acid, regulate the inflammatory response has not been well investigated. In this study, we found that a high concentration of palmitic acid induced J774A.1 murine macrophages toward a pro-inflammatory state, possibly through the activation of the TLR2 or TLR4 genes, and their downstream signaling pathways. In contrast, palmitoleic acid induced a protective effect against inflammation in macrophage of non-obese rodents by inducing an alternative activation pathway via reducing TLR2 or TLR4 signaling. This study indicates that the balance of palmitic acid (saturated fatty acid) and palmitoleic acid (monounsaturated fatty acid) effects macrophage activation. The potential therapeutic impact of palmitoleic acid to ameliorate non-obese-mediated inflammation warrants further investigation.
Topics: Animals; Anti-Infective Agents; Cell Line; Fatty Acids, Monounsaturated; Gene Expression Regulation; Macrophage Activation; Macrophages; Mice; Palmitic Acid; Rats; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
PubMed: 33930845
DOI: 10.1016/j.plefa.2021.102270 -
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 -
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