-
Journal of Cardiovascular Pharmacology Oct 2017Biologically active epoxyeicosatrienoic acid (EET) regioisomers are synthesized from arachidonic acid by cytochrome P450 epoxygenases of endothelial, myocardial, and... (Review)
Review
Biologically active epoxyeicosatrienoic acid (EET) regioisomers are synthesized from arachidonic acid by cytochrome P450 epoxygenases of endothelial, myocardial, and renal tubular cells. EETs relax vascular smooth muscle and decrease inflammatory cell adhesion and cytokine release. Renal EETs promote sodium excretion and vasodilation to decrease hypertension. Cardiac EETs reduce infarct size after ischemia-reperfusion injury and decrease fibrosis and inflammation in heart failure. In diabetes, EETs improve insulin sensitivity, increase glucose tolerance, and reduce the renal injury. These actions of EETs emphasize their therapeutic potential. To minimize metabolic inactivation, 14,15-EET agonist analogs with stable epoxide bioisosteres and carboxyl surrogates were developed. In preclinical rat models, a subset of agonist analogs, termed EET-A, EET-B, and EET-C22, are orally active with good pharmacokinetic properties. These orally active EET agonists lower blood pressure and reduce cardiac and renal injury in spontaneous and angiotensin hypertension. Other beneficial cardiovascular actions include improved endothelial function and cardiac antiremodeling actions. In rats, EET analogs effectively combat acute and chronic kidney disease including drug- and radiation-induced kidney damage, hypertension and cardiorenal syndrome kidney damage, and metabolic syndrome and diabetes nephropathy. The compelling preclinical efficacy supports the prospect of advancing EET analogs to human clinical trials for kidney and cardiovascular diseases.
Topics: 8,11,14-Eicosatrienoic Acid; Administration, Oral; Animals; Blood Pressure; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Humans; Hypertension; Kidney Diseases; Muscle, Smooth, Vascular; Structure-Activity Relationship; Vasodilation
PubMed: 28937442
DOI: 10.1097/FJC.0000000000000523 -
Frontiers in Endocrinology 2022The aim of this study was to investigate the metabolic differences between invasive and non-invasive nonfunctioning pituitary adenomas (NFPAs), determine the expression...
OBJECTIVE
The aim of this study was to investigate the metabolic differences between invasive and non-invasive nonfunctioning pituitary adenomas (NFPAs), determine the expression of an M2 macrophage marker in NFPAs, and analyze the effects of metabolic changes in invasive NFPAs on M2 macrophage infiltrates.
METHODS
Tissue samples of NFPAs from patients who underwent transsphenoidal or craniotomy surgery from January 2021 to August 2021 were collected. NFPA tissues were analyzed based on a gas chromatography-mass spectrometry non-targeted metabolomics platform, and immunohistochemical staining for M2 macrophage marker CD206 was performed.
RESULTS
We evaluated 15 invasive and 21 non-invasive NFPAs. A total of 22 metabolites were identified through non-targeted metabolomics analysis. Among them, the expression of 1-octadecanol, inosine 5'-monophosphate, adenosine 5'-monophosphate, guanosine 5'-monophosphate, creatinine, desmosterol, taurine, hypotaurine, lactic acid, and succinic acid was upregulated in invasive NFPAs, while that of 1-oleoylglycerol, arachidonic acid, cis-11-eicosenoic acid, docosahexaenoic acid, glyceric acid, hypoxanthine, linoleic acid, lysine, oleic acid, uracil, valine, and xanthine was downregulated. Immunohistochemical analysis suggested that the number of CD206-positive cells was higher in invasive NFPAs than in non-invasive NFPAs.
CONCLUSION
Invasive and non-invasive NFPAs showed distinct metabolite profiles. The levels of succinic acid and lactic acid were higher in invasive NFPAs, and the high expression of the M2 macrophage marker was verified in invasive NFPAs.
Topics: Adenoma; Biomarkers; Humans; Lactic Acid; Macrophages; Pituitary Neoplasms; Succinic Acid
PubMed: 35898456
DOI: 10.3389/fendo.2022.901884 -
Animal Bioscience Oct 2022The objective of this study was to identify polymorphism in olfactomedin like 3 (OLFML3) gene, and association analysis with meat quality, carcass characteristics,...
Association study and expression analysis of olfactomedin like 3 gene related to meat quality, carcass characteristics, retail meat cut, and fatty acid composition in sheep.
OBJECTIVE
The objective of this study was to identify polymorphism in olfactomedin like 3 (OLFML3) gene, and association analysis with meat quality, carcass characteristics, retail meat cut, and fatty acid composition in sheep, and expression quantification of OLFML3 gene in phenotypically divergent sheep.
METHODS
A total of 328 rams at the age of 10 to 12 months with an average body weight of 26.13 kg were used. A novel polymorphism was identified using high-throughput sequencing in sheep and genotyping of OLFML3 polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Among 328 rams, 100 rams representing various sheep genotypes were used for association study and proc general linear model was used to analyse association between genotypes and phenotypic traits. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for the expression analysis of OLFML3 mRNA in phenotypically divergent sheep population.
RESULTS
The findings revealed a novel polymorphism in the OLFML3 gene (g.90317673 C>T). The OLFML3 gene revealed three genotypes: CC, CT, and TT. The single nucleotide polymorphism (SNP) was found to be significantly (p<0.05) associated with meat quality traits such as tenderness and cooking loss; carcass characteristics such as carcass length; retail meat cut such as pelvic fat in leg, intramuscular fat in loin and tenderloin, muscle in flank and shank; fatty acids composition such as tridecanoic acid (C13:0), palmitoleic acid (C16:1), heptadecanoic acid (C17:0), ginkgolic acid (C17:1), linolenic acid (C18:3n3), arachidic acid (C20:0), eicosenoic acid (C20:1), arachidonic acid (C20:4n6), heneicosylic acid (C21:0), and nervonic acid (C24:1). The TT genotype was associated with higher level of meat quality, carcass characteristics, retail meat cut, and some fatty acids composition. However, the mRNA expression analysis was not different among genotypes.
CONCLUSION
The OLFML3 gene could be a potential putative candidate for selecting higher quality sheep meat, carcass characteristics, retail meat cuts, and fatty acid composition in sheep.
PubMed: 35507851
DOI: 10.5713/ab.21.0406 -
Journal of Clinical Sleep Medicine :... Feb 2022Obstructive sleep apnea (OSA) is a clinical syndrome characterized by recurrent episodes of apnea or hypopnea of the upper airway, leading to increased negative...
STUDY OBJECTIVES
Obstructive sleep apnea (OSA) is a clinical syndrome characterized by recurrent episodes of apnea or hypopnea of the upper airway, leading to increased negative intrathoracic pressure, sleep fragmentation, intermittent hypoxia during sleep, and increased risk for morbidity and mortality of affected patients. The gut microbiome plays a key role in OSA pathogenesis, and fecal metabolic profiling reflects the gut microbial functional readout and mediates host-microbiome interactions.
METHODS
Herein, we conducted a cohort study to explore fecal metabolic signatures distinguishing OSA (44 patients) from healthy controls (22 healthy controls) by untargeted gas chromatography-time-of-flight mass spectroscopy.
RESULTS
Significant metabolic signatures were detected in stool samples of patients with OSA: 246 metabolites of 24 ontology classes were identified, and 48 metabolites of 6 ontology classes were shifted. An enrichment of arachidonic acid, docosahexaenoic acid, and 11Z-eicosenoic acid and reduction in stearic acid, 5-hydroxyindoleacetic acid, gluconic acid, and α-hyodeoxycholic acid were observed in stool samples from patients with OSA. Fecal variance resulted in alterations in potential metabolic activities and was thereby strongly associated with host phenotypes, such as pulse blood oxygen saturation and apnea-hypopnea index. The prediction model based on feces metabolomics was established to distinguish OSA from healthy controls with high accuracy.
CONCLUSIONS
This study revealed the metabolomic signatures of patients with OSA in feces, and the findings provide evidence of an association between metabolome and OSA.
CITATION
Dong Y, Wang P, Lin J, et al. Characterization of fecal metabolome changes in patients with obstructive sleep apnea. . 2022;18(2):575-586.
Topics: Cohort Studies; Feces; Humans; Metabolome; Metabolomics; Sleep Apnea, Obstructive
PubMed: 34534066
DOI: 10.5664/jcsm.9668 -
Journal of Oleo Science May 2021The n-3 type polyunsaturated fatty acids (n-3PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), from fish oil exhibit health benefits such as...
The n-3 type polyunsaturated fatty acids (n-3PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), from fish oil exhibit health benefits such as triacylglycerol- and cholesterol-lowering effects. Some pelagic fishes contain long-chain monounsaturated fatty acids (LC-MUFAs) such as eicosenoic acid (C20:1), which exert health-promoting effects. However, no study has evaluated beneficial effects of n-3PUFA and LC-MUFA combination. Here, we investigated effects of simultaneous treatment with n-3PUFA (EPA and DHA) and LC-MUFA (cis-5-C20:1 and cis-7-C20:1) and found that n-3PUFA and LC-MUFA combination significantly decreased lipid accumulation and reduced total cholesterol in HepG2 cells. Cholesterol level was significantly lower in DHA + cis-7-C20:1 group than in DHA + EPA group. These results suggest the importance of LC-MUFA as a functional molecule in fish oil.
Topics: Cholesterol; Docosahexaenoic Acids; Drug Combinations; Drug Synergism; Eicosapentaenoic Acid; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fish Oils; Hep G2 Cells; Humans; Lipid Metabolism
PubMed: 33840667
DOI: 10.5650/jos.ess20341 -
Gastroenterology May 2024Gastric carcinogenesis develops within a sequential carcinogenic cascade from precancerous metaplasia to dysplasia and adenocarcinoma, and oncogenic gene activation can...
BACKGROUND & AIMS
Gastric carcinogenesis develops within a sequential carcinogenic cascade from precancerous metaplasia to dysplasia and adenocarcinoma, and oncogenic gene activation can drive the process. Metabolic reprogramming is considered a key mechanism for cancer cell growth and proliferation. However, how metabolic changes contribute to the progression of metaplasia to dysplasia remains unclear. We have examined metabolic dynamics during gastric carcinogenesis using a novel mouse model that induces Kras activation in zymogen-secreting chief cells.
METHODS
We generated a Gif-rtTA;TetO-Cre;Kras (GCK) mouse model that continuously induces active Kras expression in chief cells after doxycycline treatment. Histologic examination and imaging mass spectrometry were performed in the GCK mouse stomachs at 2 to 14 weeks after doxycycline treatment. Mouse and human gastric organoids were used for metabolic enzyme inhibitor treatment. The GCK mice were treated with a stearoyl- coenzyme A desaturase (SCD) inhibitor to inhibit the fatty acid desaturation. Tissue microarrays were used to assess the SCD expression in human gastrointestinal cancers.
RESULTS
The GCK mice developed metaplasia and high-grade dysplasia within 4 months. Metabolic reprogramming from glycolysis to fatty acid metabolism occurred during metaplasia progression to dysplasia. Altered fatty acid desaturation through SCD produces a novel eicosenoic acid, which fuels dysplastic cell hyperproliferation and survival. The SCD inhibitor killed both mouse and human dysplastic organoids and selectively targeted dysplastic cells in vivo. SCD was up-regulated during carcinogenesis in human gastrointestinal cancers.
CONCLUSIONS
Active Kras expression only in gastric chief cells drives the full spectrum of gastric carcinogenesis. Also, oncogenic metabolic rewiring is an essential adaptation for high-energy demand in dysplastic cells.
Topics: Animals; Stomach Neoplasms; Humans; Fatty Acids; Proto-Oncogene Proteins p21(ras); Energy Metabolism; Organoids; Mice; Metaplasia; Disease Models, Animal; Carcinogenesis; Chief Cells, Gastric; Cell Transformation, Neoplastic; Mice, Transgenic; Glycolysis; Adenocarcinoma; Disease Progression; Precancerous Conditions
PubMed: 38272100
DOI: 10.1053/j.gastro.2024.01.027 -
Plant Diversity Feb 2021Nervonic acid (NA, cis-15-tetracosenoic acid) is a very long-chain monounsaturated fatty acid that has been shown to be a core component of nerve fibers and nerve cells....
Nervonic acid (NA, cis-15-tetracosenoic acid) is a very long-chain monounsaturated fatty acid that has been shown to be a core component of nerve fibers and nerve cells. It can be used to treat and prevent many neurological diseases. At present, commercially available NA is mainly derived from seeds, which contain about 5%-6% NA in their seed oil. The aim of this study were to identify and analyze NA-containing species that could be used as NA resource plants. For this purpose, 46 species seeds were collected in China and in some or all of the seed oils from these species 15 fatty acids were detected, including linoleic acid, oleic acid (C18:1, C18:1), erucic acid, palmitic acid, NA, linolenic acid (C18:3, C18:3), eicosenoic acid (C20:1, C20:1), stearic acid, behenic acid, tetracosanoic acid, arachidic acid, and docosadienoic acid. Nervonic acid was detected in all samples, but the content was highly variable among species. NA content over 9% was detected in eleven species, of which had the highest levels (13.90%). The seed oil content, seed weight, and fatty acid profiles varied among species, but the comprehensive evaluation value (W) showed that could be a new potential NA resources plant. The results also showed that NA was significantly negatively correlated with palmitic acid, oleic acid, and eicosenoic acid, but positively correlated with eicosadienoic acid, behenic acid, erucic acid, and tetracosanoic acid, which indicate the probable pathway for NA biosynthesis in plants. This study has identified species that may serve as NA resources and will help guide subsequent species breeding programs.
PubMed: 33778229
DOI: 10.1016/j.pld.2020.10.003 -
Journal of Oleo Science Apr 2022The study aims to identify the fatty acid composition in Prinsepia utilis seeds collected from diverse populations of Western Himalaya, India. The seeds contained higher...
The study aims to identify the fatty acid composition in Prinsepia utilis seeds collected from diverse populations of Western Himalaya, India. The seeds contained higher saturated fatty acid (SFA-43.09%; Average of all populations) followed by polyunsaturated fatty acid (PUFA - 29.57%) and monounsaturated fatty acid (MUFA - 25.53%), however variations among growing populations was measured. The correlation analysis reveals a significant (p < 0.05) negative connection between 10-Octadecenoic acid methyl ester (FA1), and altitude. Edaphic factors like available nitrogen showed significantly (p < 0.05) but the negative correlation with cis-11-Eicosenoic acid, methyl ester (FA10; p < 0.001), Docosanoic acid, methyl ester (FA11; p < 0.05), Heptadecanoic acid, methyl ester (FA14; p < 0.05), and Tricosanoic acid, methyl ester (FA29; p < 0.05). Antioxidant activity did not show any variation in the seed oil of different populations but varied among the concentrations (5-50 µL) used. IC values of DPPH activity was significantly (p < 0.05) varied connect ranged from 11.31-24.21 µL/mL among the different populations. These variations in fatty acid composition and IC values of the DPPH activity can be one of the indicators for selecting a promising population that would be harnessed for its potential in nutraceuticals and cosmeceuticals industries.
Topics: Antioxidants; Dietary Supplements; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; India; Seeds
PubMed: 35283413
DOI: 10.5650/jos.ess21262 -
Genes Oct 2022Bladder cancer (BLCA) is a common malignancy of the urinary system. The gut microbiome produces various metabolites that play functional roles in tumorigenesis and tumor...
Bladder cancer (BLCA) is a common malignancy of the urinary system. The gut microbiome produces various metabolites that play functional roles in tumorigenesis and tumor progression. However, the integrative analysis of the gut microbiome and metabolome in BLCA has still been lacking. Thus, the aim of this study was to identify microbial and functional characteristics and metabolites in BLCA in a Chinese population. Metagenomics, targeted metabolomics, bioinformatics, and integrative analysis were used in fecal samples of BLCA patients and healthy individuals. We found gut microbiomes were significantly dysregulated in BLCA patients, including , , , , and . We also found 11Z-eicosenoic acid, 3-methoxytyrosine, abrine, aniline-2-sulfonate, arachidic acid, conjugated linoleic acids, elaidic acid, glycylleucine, glycylproline, leucyl-glycine, linoelaidic acid, linoleic acid, nicotinamide hypoxanthine dinucleotide, oleic acid, petroselinic acid, and ricinoleic acid to be significantly decreased, while cholesterol sulfate was significantly increased in BLCA patients. Integration of metagenomics and metabolomics revealed interactions between gut microbiota and metabolites and the host. We identified the alterations of gut microbiomes and metabolites in BLCA in a Chinese population. Moreover, we preliminarily revealed the associations between specific gut microbiomes and metabolites. These findings determined potential causative links among gut dysbiosis, dysregulated metabolites, and BLCA.
Topics: Humans; Metagenome; Urinary Bladder Neoplasms; Metabolome; Metabolomics; China
PubMed: 36360204
DOI: 10.3390/genes13111967 -
Molecules (Basel, Switzerland) Aug 2021Propolis is a resinous natural product collected by honeybees ( and others) from tree exudates that has been widely used in folk medicine. The present study was carried...
Propolis is a resinous natural product collected by honeybees ( and others) from tree exudates that has been widely used in folk medicine. The present study was carried out to investigate the fatty acid composition, chemical constituents, antioxidant, and xanthine oxidase (XO) inhibitory activity of Jordanian propolis, collected from Al-Ghour, Jordan. The hexane extract of Jordanian propolis contained different fatty acids, which are reported for the first time by using GC-FID. The HPLC was carried out to identify important chemical constituents such as fatty acids, polyphenols and α-tocopherol. The antioxidant and xanthine oxidase inhibitory activities were also monitored. The major fatty acid identified were palmitic acid (44.6%), oleic acid (18:1∆, 24.6%), arachidic acid (7.4%), stearic acid (5.4%), linoleic acid (18:2∆, 3.1%), caprylic acid (2.9%), lignoceric acid (2.6%), -11,14-eicosaldienoic acid (20:2∆, 2.4%), palmitoleic acid (1.5%), -11-eicosenoic acid (1.2%), α-linolenic acid (18:3∆, 1.1%), -13,16-docosadienoic acid (22:2∆, 1.0%), along with other fatty acids. The major chemical constituents identified using gradient HPLC-PDA analysis were pinocembrin (2.82%), chrysin (1.83%), luteolin-7--glucoside (1.23%), caffeic acid (1.12%), caffeic acid phenethyl ester (CAPE, 0.79%), apigenin (0.54%), galangin (0.46%), and luteolin (0.30%); while the minor constituents were hesperidin, quercetin, rutin, and vanillic acid. The percentage of α-tocopherol was 2.01 µg/g of the lipid fraction of propolis. Antioxidant properties of the extracts were determined via DPPH radical scavenging. The DPPH radical scavenging activities (IC) of different extracts ranged from 6.13 to 60.5 µg/mL compared to ascorbic acid (1.21 µg/mL). The xanthine oxidase inhibition (IC) ranged from 75.11 to 250.74 µg/mL compared to allopurinol (0.38 µg/mL). The results indicate that the various flavonoids, phenolic compounds, α-tocopherol, and other constituents which are present in propolis are responsible for the antioxidant and xanthine oxidation inhibition activity. To evaluate the safety studies of propolis, the pesticide residues were also monitored by LC-MS-MS 4500 Q-Trap. Trace amounts of pesticide residue (ng/mL) were detected in the samples, which are far below the permissible limit as per international guidelines.
Topics: Antioxidants; Caffeic Acids; Chromatography, High Pressure Liquid; Chromatography, Liquid; Fatty Acids; Flavonoids; Free Radical Scavengers; Pesticide Residues; Phenols; Phenylethyl Alcohol; Propolis; Rutin
PubMed: 34443664
DOI: 10.3390/molecules26165076