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Cancer Investigation Sep 2023Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers, closely associated with cirrhosis and fibrosis. This study aimed to assess the antitumor...
Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers, closely associated with cirrhosis and fibrosis. This study aimed to assess the antitumor activity of oleic acid-liposomes (uncoated liposomes) upon coating with albumin against HCC. The studies revealed the high safety of the prepared uncoated and albumin-coated liposomes to normal HFB-4 cells (EC of 35.57 ± 0.17 and 79.133 ± 2.92 µM, respectively) with significant anticancer activity against HepG-2 cells with IC of 56.29 ± 0.91 and 26.74 ± 0.64 µM, respectively. The albumin-coated liposomes revealed superior apoptosis induction potential (80.7%) with significant upregulation of p53 gene expression (7.0-fold), compared to OA. The study revealed that the administration of uncoated or albumin-coated liposomes (100 mg/kg) for six weeks markedly retarded the DENA-induced HCC in Wistar albino rates through regulating the liver enzymes, total bilirubin level, pro-inflammatory cytokines, and oxidative stress. Accordingly, the current study supports the and chemo-preventive feature of albumin-coated liposomes against HCC through modulation of apoptosis, improvement of the immune response, reduction of inflammation, and restoration of impaired oxidative stress, which is the first reported to the best of our knowledge.
Topics: Humans; Carcinoma, Hepatocellular; Liposomes; Liver Neoplasms; Oleic Acid; Albumins
PubMed: 37486094
DOI: 10.1080/07357907.2023.2241083 -
Journal of Agricultural and Food... Oct 2023Obesity and its associated conditions, such as nonalcoholic fatty liver disease (NAFLD), are risk factors for health. The aim of this study was to explore the effects of...
Obesity and its associated conditions, such as nonalcoholic fatty liver disease (NAFLD), are risk factors for health. The aim of this study was to explore the effects of glutamine (Gln) on liver steatosis induced by a high-fat diet (HFD) and HEPG2 cells induced by oleic acid. Gln demonstrated a positive influence on hepatic homeostasis by suppressing acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) and promoting sirtuin 1 (SIRT1) expression while improving glucose metabolism by regulating serine/threonine protein kinase (AKT)/factor forkhead box O1 (FOXO1) signals in vivo and in vitro. Obese Gln-fed mice had higher colonic short-chain fatty acid (SCFA) contents and lower inflammation factor protein levels in the liver, HEPG2 cells, and jejunum. Gln-treated obese mice had an effective decrease in abundance. These findings indicate that Gln serves as a nutritional tool in managing obesity and related disorders.
Topics: Animals; Mice; Mice, Obese; Glutamine; Diet, High-Fat; Gastrointestinal Microbiome; Liver; Non-alcoholic Fatty Liver Disease; Lipid Metabolism; Obesity; Glycolipids; Mice, Inbred C57BL
PubMed: 37847053
DOI: 10.1021/acs.jafc.3c05566 -
PloS One 2024On a global scale, lung cancer(LC) is the most commonly occurring form of cancer. Nonetheless, the process of screening and detecting it in its early stages presents...
On a global scale, lung cancer(LC) is the most commonly occurring form of cancer. Nonetheless, the process of screening and detecting it in its early stages presents significant challenges. Earlier research endeavors have recognized metabolites as potentially reliable biomarkers for LC. However, the majority of these studies have been limited in scope, featuring inconsistencies in terms of the relationships and levels of association observed.Moreover, there has been a lack of consistency in the types of biological samples utilized in previous studies. Therefore, the main objective of our research was to explore the correlation between metabolites and Non-small cell lung cancer (NSCLC).Thorough two-sample Mendelian randomization (TSMR) analysis, we investigated potential cause-and-effect relationships between 1400 metabolites and the risk of NSCLC.The analysis of TSMR revealed a significant causal impact of 61 metabolites on NSCLC.To ensure the reliability and validity of our findings, we perform FDR correction for P-values by Benjaminiand Hochberg(BH) method, Our results indicate that Oleate/vaccenate (18:1) levels and Caffeine to paraxanthine ratio may be causally associated with an increased risk of NSCLC [Oleate/vaccenate(18:1)levels: OR = 1.171,95%CI: 1.085-1.265, FDR = 0.036; Caffeine to paraxanthine ratio: OR = 1.386, 95%CI:1.191-1.612,FDR = 0.032].
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Caffeine; Mendelian Randomization Analysis; Oleic Acid; Reproducibility of Results; Genome-Wide Association Study
PubMed: 38517880
DOI: 10.1371/journal.pone.0300904 -
PeerJ 2023Forkhead box a2 (Foxa2) is proven to be an insulin-sensitive transcriptional regulator and affects hepatic steatosis. This study aims to investigate the mechanism by...
OBJECTIVE
Forkhead box a2 (Foxa2) is proven to be an insulin-sensitive transcriptional regulator and affects hepatic steatosis. This study aims to investigate the mechanism by which Foxa2 affects nonalcoholic fatty liver disease (NAFLD).
METHODS
Animal and cellular models of NAFLD were constructed using high-fat diet (HFD) feeding and oleic acid (OA) stimulation, respectively. NAFLD mice received tail vein injections of either an overexpressing negative control (oe-NC) or Foxa2 (oe-Foxa2) for four weeks. HepG2 cells were transfected with oe-NC and oe-Foxa2 for 48 h before OA stimulation. Histological changes and lipid accumulation were assessed using hematoxylin-eosin staining and oil red O staining, respectively. Expression of Foxa2, NF-κB/IKK pathway proteins, lipid synthesis proteins, and fatty acid β-oxidation protein in HFD mice and OA-induced HepG2 cells was detected using western blot.
RESULTS
Foxa2 expression was downregulated in HFD mice and OA-induced HepG2 cells. Foxa2 overexpression attenuated lipid accumulation and liver injury, and reduced the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, or triglyceride in HFD mice and OA-induced HepG2 cells. Moreover, Foxa2 overexpression decreased the expression of lipid synthesis proteins and increased fatty acid β-oxidation protein expression in the liver tissues. Furthermore, overexpression of Foxa2 downregulated the expression of p-NF-κB/NF-κB and p-IKK/IKK in OA-induced HepG2 cells. Additionally, lipopolysaccharide (NF-κB/IKK pathway activator) administration reversed the downregulation of lipid synthesis proteins and the upregulation of fatty acid β-oxidation protein.
CONCLUSION
Foxa2 expression is downregulated in NAFLD. Foxa2 ameliorated hepatic steatosis and inhibited the activation of the NF-κB/IKK signaling pathway.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; NF-kappa B; Signal Transduction; Oleic Acid; Hepatocyte Nuclear Factor 3-beta
PubMed: 38084145
DOI: 10.7717/peerj.16466 -
European Journal of Clinical Nutrition Apr 2024Prior observational studies have suggested correlations between saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) with cognitive function. However,...
BACKGROUND
Prior observational studies have suggested correlations between saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) with cognitive function. However, causal relationships remains unclear.
METHODS
We assessed the causal impact of two SFAs (palmitic acid [PA] and stearic acid [SA]) and two MUFAs (oleic acid [OA] and palmitoleic acid [POA]) on cognitive function-related traits, and dementia-related traits by univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses.
RESULTS
UVMR indicated β of 0.060 (P = 4.05E-06) for cognitive performance score and 0.066 (P = 4.21E-04) for fluid intelligence per standard deviation (SD) increase in OA level. MVMR indicated: (i) β of -0.608 (P = 8.37E-05) for fluid intelligence score per SD increase in POA; (ii) β of 0.074 (P = 0.018) for fluid intelligence score per SD increase in OA; (iii) β of 0.029 (P = 0.033) for number of incorrect matches in round per SD increase in PA; and (iv) β of 0.039 (P = 0.032) for number of incorrect matches in round per SD increase in SA. In addition, a secondary MVMR analysis after excluding the effect of polyunsaturated fatty acids suggested that: (i) β of -0.043 (P = 1.97E-02) for cognitive performance score per SD increase in PA and (ii) β of -0.079 (P = 1.79E-03) for cognitive performance score per SD increase in SA.
CONCLUSIONS
Overall, UVMR and MVMR suggest that OA may be beneficial for cognitive function, while POA, PA, and SA may have detrimental effects on cognitive function.
PubMed: 38632331
DOI: 10.1038/s41430-024-01437-5 -
Food Chemistry Aug 2024Esterification of anthocyanins with saturated fatty acids have been widely investigated, while that with unsaturated fatty acids is little understood. In this study,...
Esterification of anthocyanins with saturated fatty acids have been widely investigated, while that with unsaturated fatty acids is little understood. In this study, crude extract (purity ∼ 35 %) of cyanidin-3-O-glucoside (C3G) from black bean seed coat was utilized as reaction substrate, and enzymatically acylated with unsaturated fatty acid (oleic acid). Optimization of various reaction parameters finally resulted in the highest acylation rate of 54.3 %. HPLC-MS/MS and NMR analyses elucidated the structure of cyanidin-3-O-glucoside-oleic acid ester (C3G-OA) to be cyanidin-3-O-(6″-octadecene)-glucoside. Introduction of oleic acid into C3G improved the lipophilicity, antioxidant ability, and antibacterial activity. Further, the color and substance stability analyses showed that the susceptibility of C3G and C3G-OA to different thermal, peroxidative, and illuminant treatments were highly pH dependent, which suggested individual application guidelines. Moreover, C3G-OA showed lower toxicity to normal cell (QSG-7701) and better inhibitory effect on the proliferation of HepG2 cells than C3G, which indicated its potential anti-tumor bioactivity.
Topics: Anthocyanins; Humans; Oleic Acid; Esterification; Plant Extracts; Antioxidants; Hep G2 Cells; Phaseolus; Anti-Bacterial Agents; Molecular Structure
PubMed: 38520989
DOI: 10.1016/j.foodchem.2024.139079 -
Journal of Oleo Science 2024Unsaturated fatty acids, such as oleic and linoleic acids, are easily oxidized by exposure to temperature and light in the presence of air to form unsaturated fatty acid... (Comparative Study)
Comparative Study
Unsaturated fatty acids, such as oleic and linoleic acids, are easily oxidized by exposure to temperature and light in the presence of air to form unsaturated fatty acid hydroperoxides as primary oxidation products. However, the catabolic rates of unsaturated fatty acid hydroperoxides in the human body remain unknown. In this study, ethyl esters of C-labeled linoleic acid (*C18:2-EE) and oleic acid (*C18:1-EE) and their hydroperoxides (*C18:2-EE-OOH and *C18:1-EE-OOH, respectively) prepared by the photo-oxidation of *C18:2-EE and *C18:1-EE, respectively, were administered to mice and their catabolic rates were determined by measuring the expired CO levels. *C18:2-EE-OOH and *C18:1-EE-OOH were β-oxidized faster than *C18:2-EE and *C18:1-EE, respectively. Notably, rapid β-oxidation of *C18:2-EE-OOH and *C18:1-EE-OOH was similar to that of medium-chain fatty acids, such as octanoic acid. Then, degradation products of C18:2-EE-OOH and C18:1-EE-OOH were analyzed under gastric conditions by gas chromatography/mass spectrometry. Major decomposition products of C18:2-EE-OOH and C18:1-EE-OOH were medium-chain compounds, such as octanoic acid ethyl ester, 9-oxo-nonanoic acid ethyl ester, and 10-oxo-8-decenoic acid ethyl esters, indicating that C18:2-EE-OOH and C18:1-EE-OOH isomers formed during photo-oxidation were decomposed under acidic conditions. These findings support previous reports that dietary lipid hydroperoxides are not absorbed into the intestine as lipid hydroperoxides but as degradation products. This is the first study to suggest that dietary lipid hydroperoxides decompose during gastric digestion to form medium-chain compounds that are directly absorbed into the liver via the portal vein and rapidly catabolized via β-oxidation.
Topics: Animals; Oxidation-Reduction; Oleic Acid; Linoleic Acid; Carbon Dioxide; Carbon Isotopes; Mice; Male; Hydrogen Peroxide
PubMed: 38825538
DOI: 10.5650/jos.ess23236 -
Food Research International (Ottawa,... Oct 2023In this study, the effects of starch- oleic acid (OA)- chlorogenic acid (CA) molecular interaction on OA oxidation during thermal processing were investigated based on...
Introduction of chlorogenic acid into thermal processed starch- oleic acid system controls the ordered structure and inhibits oleic acid oxidation through molecular interactions.
In this study, the effects of starch- oleic acid (OA)- chlorogenic acid (CA) molecular interaction on OA oxidation during thermal processing were investigated based on structural analysis, oxidation characteristics and quantum calculations. The results showed that in the ternary system, on the one hand, OA could enter the spiral cavity of starch through hydrophobic forces and form V-type crystalline structure, which delayed its oxidation. On the other hand, CA could further inhibit the oxidation of OA through free radical reaction and did not affect the molecular interactions between OA and starch due to the steric hindrance and hydrophily. Notably, starch-OA-CA interactions could effectively decrease total oxidation value (19.07), prolong the induction time of oxidation (114.6 min) and reduce the abundance of oxidation products through hydrogen atom transfer reactions with active phenolic hydroxyl to protect the α-methylene groups at C=C. Overall, these results provided insights into functional property regulation by the interaction of starch-based multi-component systems.
Topics: Chlorogenic Acid; Oleic Acid; Hydroxyl Radical; Oxidation-Reduction; Starch
PubMed: 37689918
DOI: 10.1016/j.foodres.2023.113164 -
Journal of Molecular Cell Biology Apr 2024Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the commonest causes of liver dysfunction. Adipose triglyceride lipase (ATGL) is...
Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the commonest causes of liver dysfunction. Adipose triglyceride lipase (ATGL) is closely related to lipid turnover and hepatic steatosis as the speed-limited triacylglycerol lipase in liver lipolysis. However, the expression and regulation of ATGL in NAFLD remain unclear. Herein, our results showed that ATGL protein levels were decreased in the liver tissues of high-fat diet (HFD)-fed mice, naturally obese mice, and cholangioma/hepatic carcinoma patients with hepatic steatosis, as well as in the oleic acid-induced hepatic steatosis cell model, while ATGL mRNA levels were not changed. ATGL protein was mainly degraded through the proteasome pathway in hepatocytes. Beta-transducin repeat containing (BTRC) was upregulated and negatively correlated with the decreased ATGL level in these hepatic steatosis models. Consequently, BTRC was identified as the E3 ligase for ATGL through predominant ubiquitination at the lysine 135 residue. Moreover, adenovirus-mediated knockdown of BTRC ameliorated steatosis in HFD-fed mouse livers and oleic acid-treated liver cells via upregulating the ATGL level. Taken together, BTRC plays a crucial role in hepatic steatosis as a new ATGL E3 ligase and may serve as a potential therapeutic target for treating NAFLD.
Topics: Humans; Mice; Animals; Non-alcoholic Fatty Liver Disease; Ubiquitin-Protein Ligases; Oleic Acid; WD40 Repeats; Liver; Liver Neoplasms; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 37873692
DOI: 10.1093/jmcb/mjad064 -
Biochemical and Biophysical Research... May 2024Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear....
Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.
Topics: Humans; Hep G2 Cells; Proprotein Convertase 9; Mitophagy; Oleic Acid; Cholesterol, LDL; Fatty Liver; Lipid Metabolism; Cholesterol; Triglycerides; Protein Kinases; Ubiquitin-Protein Ligases; Liver; Dioxoles; Lignans; SOXC Transcription Factors
PubMed: 38531220
DOI: 10.1016/j.bbrc.2024.149815