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1.
Lipids ; 59(2): 41-53, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38287648

RESUMO

High-fat diets have been associated with colorectal cancer (CRC) risk, and the role of polyunsaturated fatty acids (PUFAs) has been reported to vary based on the length of PUFAs. We explored the association between dietary omega-6 and omega-3 PUFAs intake and CRC. We analyzed 865 CRC patients and 3206 controls from a case-control study of Iran (IROPICAN study). We used multivariate logistic regression models to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between PUFAs intake and CRC risk. Our results showed that gamma-linolenic acid (18:3 n-6, GLA), arachidonic acid (20:4n-6, ARA), a-linolenic acid (Cis-18:3n-3, ALA), eicosapentaenoic acid (20:5n-3, EPA), docosahexaenoic acid (22:6n-3, DHA) consumption was not associated with the risk of CRC. However, the OR of linoleic acid (18: 2n-6, LA) intake was 1.47 (95% CI 1.01-2.14, p = 0.04) for proximal colon and that of docosapentaenoic acid (22:5n-3, DPA) intake was 1.33 (95% CI 1.05-1.69, p = 0.01) for rectum. This study indicates a high level of LA is associated with an increased risk of proximal colon cancer, and DPA intake was positively associated with rectum cancer risk. Furthermore, our study noted a high intake of n-6 (from vegetable oils) compared to n-3 PUFAs (from fish and seafood) in this population. Public awareness and government support is needed to increase fish and seafood production and consumption in Iran.


Assuntos
Neoplasias Colorretais , Ácidos Graxos Ômega-3 , Animais , Humanos , Irã (Geográfico)/epidemiologia , Estudos de Casos e Controles , Ácidos Graxos Insaturados , Ácido Eicosapentaenoico , Ácidos Docosa-Hexaenoicos , Ácido Linoleico , Ácido gama-Linolênico , Ingestão de Alimentos , Neoplasias Colorretais/epidemiologia , Ácidos Graxos
2.
J Biol Chem ; 300(1): 105563, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101568

RESUMO

Intermediary metabolites and flux through various pathways have emerged as key determinants of post-translational modifications. Independently, dynamic fluctuations in their concentrations are known to drive cellular energetics in a bi-directional manner. Notably, intracellular fatty acid pools that drastically change during fed and fasted states act as precursors for both ATP production and fatty acylation of proteins. Protein fatty acylation is well regarded for its role in regulating structure and functions of diverse proteins; however, the effect of intracellular concentrations of fatty acids on protein modification is less understood. In this regard, we unequivocally demonstrate that metabolic contexts, viz. fed and fasted states, dictate the extent of global fatty acylation. Moreover, we show that presence or absence of glucose that influences cellular and mitochondrial uptake/utilization of fatty acids and affects palmitoylation and oleoylation, which is consistent with their intracellular abundance in fed and fasted states. Employing complementary approaches including click-chemistry, lipidomics, and imaging, we show the top-down control of cellular metabolic state. Importantly, our results establish the crucial role of mitochondria and retrograde signaling components like SIRT4, AMPK, and mTOR in orchestrating protein fatty acylation at a whole cell level. Specifically, pharmacogenetic perturbations that alter either mitochondrial functions and/or retrograde signaling affect protein fatty acylation. Besides illustrating the cross-talk between carbohydrate and lipid metabolism in mediating bulk post-translational modification, our findings also highlight the involvement of mitochondrial energetics.


Assuntos
Acilação , Ácidos Graxos , Metabolismo dos Lipídeos , Processamento de Proteína Pós-Traducional , Proteínas , Trifosfato de Adenosina/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Química Click , Jejum/fisiologia , Ácidos Graxos/metabolismo , Glucose/metabolismo , Lipidômica , Lipoilação , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas/química , Proteínas/metabolismo , Sirtuínas/metabolismo , Serina-Treonina Quinases TOR/metabolismo
3.
Bioengineering (Basel) ; 10(12)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38136003

RESUMO

Fatty acids have been supplied for diverse non-food, industrial applications from plant oils and animal fats for many decades. Due to the massively increasing world population demanding a nutritious diet and the thrive to provide feedstocks for industrial production lines in a sustainable way, i.e., independent from food supply chains, alternative fatty acid sources have massively gained in importance. Carbohydrate-rich side-streams of agricultural production, e.g., molasses, lignocellulosic waste, glycerol from biodiesel production, and even CO2, are considered and employed as carbon sources for the fermentative accumulation of fatty acids in selected microbial hosts. While certain fatty acid species are readily accumulated in native microbial metabolic routes, other fatty acid species are scarce, and host strains need to be metabolically engineered for their high-level production. We report the metabolic engineering of Pichia pastoris to produce palmitoleic acid from glucose and discuss the beneficial and detrimental engineering steps in detail. Fatty acid secretion was achieved through the deletion of fatty acyl-CoA synthetases and overexpression of the truncated E. coli thioesterase 'TesA. The best strains secreted >1 g/L free fatty acids into the culture medium. Additionally, the introduction of C16-specific ∆9-desaturases and fatty acid synthases, coupled with improved cultivation conditions, increased the palmitoleic acid content from 5.5% to 22%.

4.
Int J Mol Sci ; 24(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37373478

RESUMO

The seeds of Moringa oleifera (horseradish tree) contain about 40% of one of the most stable vegetable oils (Moringa seed oil). Therefore, the effects of Moringa seed oil on human SZ95 sebocytes were investigated and were compared with other vegetable oils. Immortalized human SZ95 sebocytes were treated with Moringa seed oil, olive oil, sunflower oil, linoleic acid and oleic acid. Lipid droplets were visualized by Nile Red fluorescence, cytokine secretion via cytokine antibody array, cell viability with calcein-AM fluorescence, cell proliferation by real-time cell analysis, and fatty acids were determined by gas chromatography. Statistical analysis was performed by the Wilcoxon matched-pairs signed-rank test, the Kruskal-Wallis test and Dunn's multiple comparison test. The vegetable oils tested stimulated sebaceous lipogenesis in a concentration-dependent manner. The pattern of lipogenesis induced by Moringa seed oil and olive oil was comparable to lipogenesis stimulated by oleic acid with also similar fatty acid secretion and cell proliferation patterns. Sunflower oil induced the strongest lipogenesis among the tested oils and fatty acids. There were also differences in cytokine secretion, induced by treatment with different oils. Moringa seed oil and olive oil, but not sunflower oil, reduced the secretion of pro-inflammatory cytokines, in comparison to untreated cells, and exhibited a low n-6/n-3 index. The anti-inflammatory oleic acid detected in Moringa seed oil probably contributed to its low levels of pro-inflammatory cytokine secretion and induction of cell death. In conclusion, Moringa seed oil seems to concentrate several desired oil properties on sebocytes, such as high content level of the anti-inflammatory fatty acid oleic acid, induction of similar cell proliferation and lipogenesis patterns compared with oleic acid, lipogenesis with a low n-6/n-3 index and inhibition of secretion of pro-inflammatory cytokines. These properties characterize Moringa seed oil as an interesting nutrient and a promising ingredient in skin care products.


Assuntos
Moringa oleifera , Moringa , Humanos , Moringa oleifera/química , Azeite de Oliva/farmacologia , Azeite de Oliva/análise , Sementes/química , Ácidos Graxos/análise , Óleos de Plantas/química , Ácido Oleico/farmacologia , Ácido Oleico/análise , Citocinas/análise
5.
Sensors (Basel) ; 23(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37177451

RESUMO

Soybean oil produces harmful substances after long durations of frying. A rapid and nondestructive identification approach for soybean oil was proposed based on photoacoustic spectroscopy and stacking integrated learning. Firstly, a self-designed photoacoustic spectrometer was built for spectral data collection of soybean oil with various frying times. At the same time, the actual free fatty acid content and acid value in soybean oil were measured by the traditional titration experiment, which were the basis for soybean oil quality detection. Next, to eliminate the influence of noise, the spectrum from 1150 cm-1 to 3450 cm-1 was selected to remove noise by ensemble empirical mode decomposition. Then three dimensionality reduction methods of principal component analysis, successive projection algorithm, and competitive adaptive reweighting algorithm were used to reduce the dimension of spectral information to extract the characteristic wavelength. Finally, an integrated model with three weak classifications was used for soybean oil detection by stacking integrated learning. The results showed that three obvious absorption peaks existed at 1747 cm-1, 2858 cm-1, and 2927 cm-1 for soluble sugars and unsaturated oils, and the model based on stacking integrated learning could improve the classification accuracy from 0.9499 to 0.9846. The results prove that photoacoustic spectroscopy has a good detection ability for edible oil quality detection.


Assuntos
Óleos de Plantas , Óleo de Soja , Óleo de Soja/análise , Óleo de Soja/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Óleos de Plantas/análise
6.
J Dairy Sci ; 106(4): 2395-2407, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36797184

RESUMO

The form of a lipid supplement, its degree of saturation, and its fatty acid (FA) profile greatly influence digestibility and cow productive response. The objective in this study was to examine the effect of fat supplements that differ in their form or FA profile on nutrient digestibility and cow performance. Forty-two mid-lactation cows (128 ± 53 d) were assigned to 3 treatment groups according to milk yield, days in milk, and body weight. For 13 wk, the cows were fed rations that contained (on a dry matter basis) (1) 2.4% of calcium salts of fatty acids (CSFA) consisting of 45% palmitic acid (PA) and 35% oleic acid (OA; CS45:35); (2) 2.4% of CSFA consisting of 80% PA and 10% OA (CS80:10); or (3) 2.0% of free FA consisting of 80% PA and 10% OA (FF80:10). Rumen samples were taken to measure the ammonia and volatile FA concentrations, and fecal samples were taken to measure the digestibility. Preplanned comparisons were CS45:35 versus CS80:10 to assess 2 CSFA supplements with different FA profiles, and CS80:10 versus FF80:10 to assess similar FA profiles in different forms. Compared with CS45:35, CS80:10 decreased the milk yields, increased the fat percentage, and tended to increase the energy-corrected milk (ECM) yields. The fat percentage of milk was highest in the FF80:10 cows (4.02%), intermediate in the CS80:10 cows (3.89%), and lowest in the CS45:35 cows (3.75%). Compared with CS80:10, FF80:10 increased milk yields (50.1 vs. 49.4 kg/d, respectively), tended to increase fat percentage, and increased 4% fat-corrected milk (4% FCM; 49.1 vs. 47.7 kg/d, respectively) and ECM yields (49.5 vs. 48.2 kg/d, respectively). Treatment had no effect on dry matter intake (DMI), and compared with CS80:10 cows, the calculated energy balance was lower in the FF80:10 cows. The 4% FCM/DMI and ECM/DMI ratios were higher in the FF80:10 group compared with the CS80:10 group. Compared with the CS80:10 cows, the FF80:10 cows had a lower rumen pH, higher propionate, lower acetate/propionate ratio, and higher total VFA. Compared with CS45:35 cows, the apparent total-tract digestibilities of neutral detergent fiber and acid detergent fiber were higher in CS80:10 cows; whereas, the apparent total-tract digestibilities of dry matter, organic matter, protein, neutral detergent fiber, and acid detergent fiber were higher in the CS80:10 cows compared with the FF80:10 cows. Compared with the CS80:10 group, the apparent digestibility of total FA was 13.0 percentage points lower in the FF80:10 cows (79.1 vs. 66.1%, respectively), and similarly, the digestibilities of 16-carbon and 18-carbon FA were lower in the FF80:10 cows than in the CS80:10 cows. In conclusion, the form, more than the FA profile of fat supplements, influenced digestibility. Further, the CSFA supplements were more digestible than the free fatty acids, regardless of the FA profile. However, energy partitioning toward production appeared to be higher in the FF80:10 cows, although the digestibility of nutrients was lower than in the CSFA product with a similar FA profile.


Assuntos
Dieta , Ácidos Graxos , Feminino , Bovinos , Animais , Ácidos Graxos/metabolismo , Dieta/veterinária , Detergentes/metabolismo , Propionatos/metabolismo , Digestão , Suplementos Nutricionais , Ácido Palmítico , Leite/metabolismo , Lactação , Ácidos Graxos não Esterificados/metabolismo , Ração Animal/análise
7.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36638067

RESUMO

Increased concentrations of free fatty acids (FFAs) induce reactive oxygen species (ROSs) generation and endoplasmic reticulum (ER) stress, thus, increasing the risk of fatty liver in dairy cows during the periparturient period. In non-ruminants, Taraxasterol (Tara; a pentacyclic triterpenoid found in medicinal plants) plays an important role in anti-inflammatory and antioxidant reactions. Whether Tara can alleviate or prevent fatty liver in ruminants is unknown. We addressed whether Tara supply could dampen lipid accumulation, ROSs production, and ER stress caused by FFAs in calf hepatocytes. Primary calf hepatocytes were isolated from five healthy calves (1 d old, female, 30-40 kg, fasting, rectal temperature 38.7-39.7 °C). In the first experiment, hepatocytes were incubated with various concentrations of Tara (2.5, 5, and 10 µg/mL) for 12 h prior to the 1.2-mM FFAs challenge. Results indicated that the level of ROSs was lowest with 5 µg/mL Tara. Thus, to further characterize the molecular mechanisms whereby Tara protects from FFAs-induced lipid deposition in calf hepatocytes, we performed incubations with 5 µg/mL Tara for 12 h prior to a 1.2-mM FFAs challenge for an additional 12 h. Results indicated that 1.2-mM FFAs challenge increased mitochondrial membrane potential (MMP), enhanced expression of proteins and mRNA associated with ER stress (PERK, IRE1, GRP78, ATF6, and CHOP) and fatty acid synthesis (FASN, ACC1, and SREBP-1c), and ultimately led to increased lipid droplet synthesis. In contrast, Tara treatment alleviated these negative effects after 1.2-mM FFAs challenge. To determine whether Tara protects against FFAs-induced lipid droplet synthesis by alleviating oxidative stress, hepatocytes were treated with 5 µg/mL Tara for 22 h prior to H2O2 (440 µM) challenge for 2 h. Compared with H2O2 treatment alone, results revealed a marked decrease in ROSs, MMP, and protein abundance of ER stress (GRP78, ATF6, and CHOP) and lipid droplet synthesis in response to Tara prior to H2O2 challenge. Data suggested that the increase in mitochondrial ROSs production contributes to lipid accumulation in calf hepatocytes. Collectively, our in vitro data indicate that Tara alleviates fatty acid-induced lipid deposition. Further research is warranted to ascertain that Tara can be helpful in the therapeutic management of early lactating cows to control or alleviate excessive hepatic lipid deposition.


Fatty liver is a common occurrence in the early postpartum period, partly due to the large influx of fatty acids into the liver during adipose tissue lipolysis. Because there is a linkage between fatty acid metabolism, oxidative stress, and lipid deposition in hepatocytes of nonruminant animals, we evaluated the potential therapeutic roles of Taraxasterol on reactive oxygen species and endoplasmic reticulum (ER) stress in vitro. This compound found in medicinal plants alleviated oxidative and ER stress and reduced lipid accumulation. Thus, it may represent a novel therapeutic tool for the management of dairy cows around parturition.


Assuntos
Doenças dos Bovinos , Fígado Gorduroso , Feminino , Bovinos , Animais , Ácidos Graxos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fígado/metabolismo , Chaperona BiP do Retículo Endoplasmático , Lactação , Peróxido de Hidrogênio/metabolismo , Metabolismo dos Lipídeos , Hepatócitos/metabolismo , Fígado Gorduroso/veterinária , Estresse do Retículo Endoplasmático , Ácidos Graxos não Esterificados/metabolismo , Doenças dos Bovinos/metabolismo
8.
J Lipid Res ; 64(3): 100337, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36716821

RESUMO

Liver function indicators are often impaired in patients with type 2 diabetes mellitus (T2DM), who present higher concentrations of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase than individuals without diabetes. However, the mechanism of liver injury in patients with T2DM has not been clearly elucidated. In this study, we performed a lipidomics analysis on the liver of T2DM mice, and we found that phosphatidylethanolamine (PE) levels were low in T2DM, along with an increase in diglyceride, which may be due to a decrease in the levels of phosphoethanolamine cytidylyltransferase (Pcyt2), thus likely affecting the de novo synthesis of PE. The phosphatidylserine decarboxylase pathway did not change significantly in the T2DM model, although both pathways are critical sources of PE. Supplementation with CDP-ethanolamine (CDP-etn) to increase the production of PE from the CDP-etn pathway reversed high glucose and FFA (HG&FFA)-induced mitochondrial damage including increased apoptosis, decreased ATP synthesis, decreased mitochondrial membrane potential, and increased reactive oxygen species, whereas supplementation with lysophosphatidylethanolamine, which can increase PE production in the phosphatidylserine decarboxylase pathway, did not. Additionally, we found that overexpression of PCYT2 significantly ameliorated ATP synthesis and abnormal mitochondrial morphology induced by HG&FFA. Finally, the BAX/Bcl-2/caspase3 apoptosis pathway was activated in hepatocytes of the T2DM model, which could also be reversed by CDP-etn supplements and PCYT2 overexpression. In summary, in the liver of T2DM mice, Pcyt2 reduction may lead to a decrease in the levels of PE, whereas CDP-etn supplementation and PCYT2 overexpression ameliorate partial mitochondrial function and apoptosis in HG&FFA-stimulated L02 cells.


Assuntos
Diabetes Mellitus Tipo 2 , Fosfatidiletanolaminas , Camundongos , Animais , Fosfatidiletanolaminas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , RNA Nucleotidiltransferases/metabolismo , Etanolaminas/farmacologia , Etanolaminas/metabolismo , Hepatócitos/metabolismo , Mitocôndrias/metabolismo , Apoptose , Trifosfato de Adenosina/metabolismo
9.
Food Chem ; 411: 135529, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36689869

RESUMO

The flowers of Quararibea funebris tree are an important component of tejate, a traditional Mexican beverage. The flowers exhibited a high concentration of total polyphenolic compounds, total carotenoids, and vitamin C. UPLC analysis revealed the presence of salicylic acid, kaemferol-3-O-glucoside, trans-cinnamic acid, rutin, scopoletin, l-phenylalanine, 4-coumaric acid and quercetin-3-glucoside, among others metabolites. The flowers exhibited volatile compounds as isolongifolene, α-cedrene, 2,5,5-trimethyl-2,3,4,5,6,7-hexahydro-1H-2,4a-ethanonaphthalene, while that linoleic acid, palmitic acid, and linolenic acid were the major fatty acids present in the oil extract. Magnesium, potassium, and calcium were the minerals most abundant in the flowers. In addition the methanolic extract of the flowers exhibited antimicrobial properties against the tested pathogenic microbial strains. In conclusion, these results showed that the Q. funebris flowers not only have an aromatic and flavoring power for the Tejate beverage, but also contains compounds with antioxidant, antimicrobial, and nutraceutical potential, which helps to explain its therapeutic uses.


Assuntos
Anti-Infecciosos , Bombacaceae , Antioxidantes/farmacologia , Antioxidantes/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Antibacterianos/farmacologia , Flores/química , Suplementos Nutricionais/análise
10.
Biosci Rep ; 43(2)2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36645186

RESUMO

BACKGROUND: Multiple studies have assessed the role of Cassiae semen (CS) in regulating lipid metabolism. However, the mechanism of action of CS on non-alcoholic fatty liver disease (NAFLD) has seen rare scrutiny. OBJECTIVE: The objective of this study was to explore the regulatory mechanism of CS on lipid metabolism in NAFLD. METHODS: Components of CS ethanol extract (CSEE) were analyzed and identified using UPLC-Q-Orbirap HRMS. The candidate compounds of CS and its relative targets were extracted from the Traditional Chinese Medicine Systems Pharmacology, Swiss-Target-Prediction, and TargetNet web server. The Therapeutic Target Database, Genecards, Online Mendelian Inheritance in Man, and DisGeNET were searched for NAFLD targets. Binding affinity between potential core components and key targets was established employing molecular docking simulations. After that, free fatty acid (FFA)-induced HepG2 cells were used to further validate part of the network pharmacology results. RESULTS: Six genes, including Caspase 3 (CASP3), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA), epidermal growth factor receptor (EGFR), and amyloid ß (A4) precursor protein (APP) were identified as key targets. The mitogen-activated protein kinase (MAPK) signaling pathway was found to associate closely with CS's effect on NAFLD. Per molecular docking findings, toralactone and quinizarin formed the most stable combinations with hub genes. About 0.1 (vs. FFA, P<0.01) and 0.2 (vs. FFA, P<0.05) mg/ml CSEE decreased lipid accumulation in vitro by reversing the up-regulation of CASP3, EGFR, and APP and the down-regulation of PIK3CA. CONCLUSION: CSEE can significantly reduce intracellular lipid accumulation by modulating the MAPK signaling pathway to decrease CASP3 and EGFR expression.


Assuntos
Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Humanos , Caspase 3 , Farmacologia em Rede , Metabolismo dos Lipídeos , Peptídeos beta-Amiloides , Simulação de Acoplamento Molecular , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Receptores ErbB , Classe I de Fosfatidilinositol 3-Quinases , Sementes , Lipídeos , Medicamentos de Ervas Chinesas/farmacologia
11.
Nutrients ; 14(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36145157

RESUMO

Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women <20 weeks' gestation, BMI ≥ 29 kg/m2. Eligible women (n = 154) were randomized to receive vitamin D3 (1600 IU/day) or placebo. Assessments were performed <20, 24−28 and 35−37 weeks and at birth. Linear regression models were used to assess effects of vitamin D on maternal and cord blood lipids. In the vitamin D group significantly higher total 25-OHD and 25-OHD3 levels were found in maternal and cord blood compared with placebo. Adjusted regression models did not reveal any differences in triglycerides, LDL-C, HDL-C, free fatty acids, ketone bodies or leptin between groups. Neonatal sum of skinfolds was comparable between the two groups, but correlated positively with cord blood 25-OH-D3 (r = 0.34, p = 0.012). Vitamin D supplementation in pregnancy increases maternal and cord blood vitamin D significantly resulting in high rates of vitamin D sufficiency. Maternal and cord blood lipid parameters were unaffected by Vitamin D3 supplementation.


Assuntos
Diabetes Gestacional , Deficiência de Vitamina D , Distribuição da Gordura Corporal , Colecalciferol/uso terapêutico , LDL-Colesterol , Diabetes Gestacional/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos não Esterificados , Feminino , Humanos , Recém-Nascido , Corpos Cetônicos , Leptina , Estilo de Vida , Obesidade , Sobrepeso , Gravidez , Resultado da Gravidez , Gestantes , Triglicerídeos , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas
12.
Molecules ; 27(15)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35956860

RESUMO

Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil-water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 µg/mL (82.4 µM) and 11.7 µg/mL (41.4 µM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management.


Assuntos
Produtos Biológicos , Sesamum , Animais , Produtos Biológicos/uso terapêutico , Gorduras na Dieta , Digestão , Ácido Linoleico/farmacologia , Lipase , Obesidade/tratamento farmacológico , Ácido Oleico/farmacologia , Orlistate/farmacologia , Ratos , Suínos , Triglicerídeos
13.
Neurochem Int ; 155: 105300, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35151771

RESUMO

The arcuate nucleus of hypothalamus (ARC) integrates circulating factors that signal energy status. The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are widely distributed in the periphery and central nervous systems (CNS) and play important roles on energy balance. The present study aimed to investigate the responses of microinjection of VIP and PACAP in the ARC on metabolic changes and food intake. In addition, the activity of neurons in the ARC following intracerebroventricular (ICV) microinjection of these peptides was also evaluated. Microinjection of VIP or PACAP in the ARC decreased fasting-induced hyperphagia and food intake, decreased total lipids, and increased free fatty acids plasma concentrations. VIP microinjection in the ARC induced hyperglycemia and decreased total cholesterol level; and PACAP reduced triglycerides concentration. ICV microinjection of VIP and PACAP enhanced neuronal activation in the ARC, associated with lower fasting-induced hyperphagia and plasma metabolic changes (only VIP). These results suggest that VIP and PACAP play important roles in ARC, inducing hypophagia and peripheral metabolic changes, as hyperglycemia, increased free fatty acids and decreased total lipids plasma levels.


Assuntos
Núcleo Arqueado do Hipotálamo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Peptídeo Intestinal Vasoativo , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Comportamento Alimentar , Hipotálamo/metabolismo , Lipídeos/sangue , Neurônios/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia
14.
Drug Chem Toxicol ; 45(1): 347-352, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31736373

RESUMO

In recent years, herbal tea consumption becomes popular because of the potential health benefits and attractive flavors. However, there is also a growing concern that herbal supplements contribute to the drug-drug/drug-herb interactions and hepatotoxicity. In this study, FL83B mouse hepatocytes were used as an in vitro mode of hepatotoxicity induced by free fatty acids, including palmitic acid (PA) and oleic acid (OA), ethanol, and acetaminophen. Herbal tea extracts were obtained from eight common herbal plants, including Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., Urtica dioica L., Hemerocallis fulva (L.) L., Citrus maxima (Burm.) Merr., Citrus limon (L.) Osbeck, and Ficus formosana Maxim. MTT assay was used to evaluate the impact of these herbal tea extracts on hepatoxocitity. We found that these herbal tea extracts per se did not exhibit hepatotoxicity, and had no effect on OA-induced hepatotoxicity. However, extracts from Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., and Hemerocallis fulva (L.) L. exhibited protective effect against PA-induced hepatotoxicity. In addition, herbal tea extracts from Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., Urtica dioica L., Hemerocallis fulva (L.) L., and Ficus formosana Maxim. exhibited protective effect against acetaminophen-induced hepatotoxicity. Interestingly, all these herbal tea extracts enhanced ethanol-induced hepatotoxicity. Our results suggest that herbal tea extracts have differential effects on different modes of hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Chás de Ervas , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Etanol/toxicidade , Ácidos Graxos não Esterificados , Hepatócitos , Camundongos , Extratos Vegetais/toxicidade
15.
Food Chem ; 374: 131793, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-34915370

RESUMO

The analysis of free fatty acids (FFAs) in edible oils, especially their fine structure, can provide information for nutritional value evaluation and authentication. Here, a strategy based on epoxidation reaction by mCPBA combined with tandem MS was developed to identify and relatively quantify FFAs, including CC location isomers, which can rapidly distinguish different edible oils. Notably, low-abundant FFAs can be detected directly in the presence of high-abundant triacylglycerol (TAG) without complicated pretreatment. We identified a series of CC location isomers via mCPBA-nanoESI-MS/MS, among them, FA 24:1 (Δ13) and FA 24:1 (Δ17) were first identified in edible oils, and the predominant UFAs was FA 18:1 (Δ9), which occupies 98.35% of FA 18:1 in peanut oil while 89.68% in rapeseed oil. The results demonstrated that the proposed method could provide further in-depth CC positional information of oils, promoting the development of structural determination of fatty acids in food chemistry.


Assuntos
Ácidos Graxos não Esterificados , Espectrometria de Massas em Tandem , Ácidos Graxos , Óleos de Plantas , Óleo de Brassica napus
16.
Microbiol Spectr ; 9(3): e0145521, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34762519

RESUMO

The bacterial pathogen Acinetobacter baumannii has emerged as an urgent threat to health care systems. The prevalence of multidrug resistance in this critical human pathogen is closely associated with difficulties in its eradication from the hospital environment and its recalcitrance to treatment during infection. The development of resistance in A. baumannii is in part due to substantial plasticity of its genome, facilitating spontaneous genomic evolution. Many studies have investigated selective pressures imposed by antibiotics on genomic evolution, but the influence of high-abundance bioactive molecules at the host-pathogen interface on mutation and rates of evolution is poorly understood. Here, we studied the roles of host fatty acids in the gain in resistance to common antibiotics. We defined the impact of the polyunsaturated fatty acids arachidonic acid and docosahexaenoic acid on the development of resistance to erythromycin in A. baumannii strain AB5075_UW using a microevolutionary approach. We employed whole-genome sequencing and various phenotypic analyses to characterize microbe-lipid-antibiotic interactions. Cells exposed to erythromycin in the presence of the fatty acids displayed significantly lower rates of development of resistance to erythromycin and, importantly, tetracycline. Subsequent analyses defined diverse means by which host fatty acids influence the mutation rates. This work has highlighted the critical need to consider the roles of host fatty acids in A. baumannii physiology and antimicrobial resistance. Collectively, we have identified a novel means to curb the development of resistance in this critical human pathogen. IMPORTANCE The global distribution of multidrug resistance in A. baumannii has necessitated seeking not only alternative therapeutic approaches but also the means to limit the development of resistance in clinical settings. Highly abundant host bioactive compounds, such as polyunsaturated fatty acids, are readily acquired by A. baumannii during infection and have been illustrated to impact the bacterium's membrane composition and antibiotic resistance. In this work, we show that in vitro supplementation with host polyunsaturated fatty acids reduces the rate at which A. baumannii gains resistance to erythromycin and tetracycline. Furthermore, we discover that the impact on resistance development is closely associated with the primary antimicrobial efflux systems of A. baumannii, which represent one of the major drivers of clinical resistance. Overall, this study emphasizes the potential of host macromolecules in novel approaches to circumvent the difficulties of multidrug resistance during A. baumannii treatment, with fatty acid supplements such as fish oil providing safe and cost-effective ways to enhance host tolerance to bacterial infections.


Assuntos
Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Ácido Araquidônico/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Eritromicina/farmacologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/crescimento & desenvolvimento , Membrana Celular/química , Genoma Bacteriano/genética , Humanos , Testes de Sensibilidade Microbiana , Taxa de Mutação , Seleção Genética/genética , Tetraciclinas/farmacologia , Sequenciamento Completo do Genoma
17.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638772

RESUMO

Free fatty acids (FFAs) are generated by the reaction of lipases with membrane lipids. Generated polyunsaturated fatty acids (PUFAs) containing more than two double bonds have toxic effects in photosynthetic organisms. In the present study, we examined the effect of exogenous FFAs in the growth medium on the activity of photosystem II (PSII) under strong light in the cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis). PUFAs but not monounsaturated fatty acids accelerated the rate of photodamage to PSII by inactivating electron transfer at the oxygen-evolving complex. Moreover, supplemented PUFAs were specifically incorporated into the sn-2 position of phosphatidylglycerol (PG), which usually contains C16 fatty acids at the sn-2 position in Synechocystis cells. The disruption of the gene for an acyl-ACP synthetase reduced the effect of PUFAs on the photoinhibition of PSII. Thus, the specific incorporation of PUFAs into PG molecules requires acyl-ACP synthetase and leads to an unstable PSII, thereby accelerating photodamage to PSII. Our results are a breakthrough into elucidating the molecular mechanism of the toxicity of PUFAs to photosynthetic organisms.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Fosfatidilgliceróis/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Synechocystis/metabolismo
18.
MethodsX ; 8: 101334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34430240

RESUMO

Acid oils and fatty acid distillates are by-products from the refining of edible oils and fats. They are used as feed ingredients, but their highly variable composition sometimes affects the productive parameters of the animals. Thus, their quality control and standardization are necessary. The official methods recommended for crude and refined fats and oils must be modified to give reliable results when applied to acid oils and fatty acid distillates. This article summarizes the drawbacks that were encountered during the setup of the analytical methods and how were they overcome by adapting the methods to these type of fat samples. Some methods such as the determinations of fatty acid composition, tocopherol and tocotrienol content, unsaponifiable matter, acidity and peroxide value had to be minimally adapted. However, others such as the determinations of moisture and volatile matter, insoluble impurities, lipid classes and p-anisidine value showed important drawbacks that required a more significant adaptation.•All the analytical methods have been successfully applied to acid oils and fatty acid distillates.•A detailed description of the sample preparation for analysis and applied analytical methods is provided as a compendium of methods in the supplementary material.•These methods will be extremely useful to improve the quality control of these heterogeneous feed ingredients.

19.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445533

RESUMO

Aeromonas spp. cause many diseases in aquaculture habitats. Hermetia illucens (Hi) larvae were used as feed-in aquacultures and in eradicating pathogenic fish bacteria. In the present study, we applied consecutive extractions of the same biomass of BSFL fat using the acidic water-methanol solution. The major constituents of the sequential extracts (SEs) were free fatty acids (FFAs), and fatty acids derivatives as identified by gas chromatography spectrometry (GC-MS). Our improved procedure enabled gradual enrichment in the unsaturated fatty acids (USFAs) content in our SEs. The present study aimed to compare the composition and antimicrobial properties of SEs. Among actual fish pathogens, A. hydrophila and A. salmonicida demonstrated multiple drug resistance (MDR) against different recommended standard antibiotics: A. salmonicida was resistant to six, while A. hydrophila was resistant to four antibiotics from ten used in the present study. For the first time, we demonstrated the high dose-dependent antibacterial activity of each SE against Aeromonas spp., especially MDR A. salmonicida. The bacteriostatic and bactericidal (MIC/MBC) activity of SEs was significantly enhanced through the sequential extractions. The third sequential extract (AWME3) possessed the highest activity against Aeromonas spp.: inhibition zone diameters were in the range (21.47 ± 0.14-20.83 ± 0.22 mm) at a concentration of 40 mg/mL, MIC values ranged between 0.09 and 0.38 mg/mL for A. hydrophila and A. salmonicida, respectively. AWME3 MBC values recorded 0.19 and 0.38 mg/mL, while MIC50 values were 0.065 ± 0.004 and 0.22 ± 0.005 mg/mL against A. hydrophila and A. salmonicida, respectively. Thus, the larvae fat from Hermitia illucens may serve as an excellent reservoir of bioactive molecules with good capacity to eradicate the multidrug-resistant bacteria, having promising potential for practical application in the aquaculture field.


Assuntos
Aeromonas/patogenicidade , Antibacterianos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ácidos Graxos/farmacologia , Doenças dos Peixes/prevenção & controle , Larva/química , Extratos de Tecidos/farmacologia , Animais , Dípteros , Doenças dos Peixes/microbiologia , Peixes
20.
Phytomedicine ; 89: 153620, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34218216

RESUMO

BACKGROUND: Xin-Ke-Shu (XKS), a commonly used traditional Chinese medicine, has been clinically proven to be effective for treatment of acute myocardial ischemia (AMI). Numerous studies underscore the important role of fatty acid metabolism in the pathogenesis of AMI. PURPOSE: This study examined the relationship between free fatty acids (FFAs) and AMI and the contributions of individual herbs found in XKS to provide a basis for the study of the compatible principle of XKS. METHODS: UFLC-MS/MS-based targeted metabolomics was performed to analyze the levels of 15 FFAs in the plasma and myocardium of isoproterenol (ISO)-induced AMI rats treated with XKS and the subtracted prescriptions of XKS. Electrocardiogram data, H&E staining, biochemical analysis and western blotting were assayed to illustrate the cardioprotection of XKS and its subtracted prescription in AMI. Correlation analysis was used to reveal the relationship between the levels of FFAs and overexpressed proteins/biochemical enzymes. RESULTS: We found aberrant fatty acid metabolism in AMI rats. In both plasma and myocardium, the concentrations of most of quantified FFAs were significantly altered, whereas the concentrations of stearic acid and behenic acid were similar between the control and AMI groups. Correlation analysis revealed that palmitic acid, oleic acid, linoleic acid and arachidonic acid were potentially the most relevant FFAs to inflammatory and apoptotic proteins and CK-MB. Moreover, XKS effectively alleviated pathological alterations, FFA metabolism abnormity, inflammation and apoptosis found in the myocardium of AMI rats. Notably, the removal of Salvia miltiorrhiza and Pueraria lobata from XKS resulted in markedly regulation loss of cardioprotection during AMI, especially mediation loss of FFA metabolism. The other three herbs of XKS also played a role in improving AMI. CONCLUSION: Fatty acid metabolism aberrance occurred during AMI. S. miltiorrhiza and P. lobata play vital roles in the anti-inflammatory and anti-apoptotic action partially by regulating FFA levels. Our findings revealed potential novel clinical FFAs for predicting AMI and extended the insights into the compatible principle of XKS in which S. miltiorrhiza and P. lobata can potently modulate FFA metabolism.


Assuntos
Medicamentos de Ervas Chinesas , Ácidos Graxos não Esterificados/metabolismo , Isquemia Miocárdica , Pueraria , Salvia miltiorrhiza , Animais , Medicamentos de Ervas Chinesas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Pueraria/química , Ratos , Salvia miltiorrhiza/química , Espectrometria de Massas em Tandem
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