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1.
Biotechnol Biofuels Bioprod ; 17(1): 32, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402213

RESUMO

BACKGROUND: Eicosapentaenoic acid (EPA) is widely used in the functional food and nutraceutical industries due to its important benefits to human health. Oleaginous microorganisms are considered a promising alternative resource for the production of EPA lipids. However, the storage of EPA in triglyceride (TG) becomes a key factor limiting its level. RESULTS: This study aimed to incorporate more EPA into TG storage through metabolic engineering. Firstly, key enzymes for TG synthesis, the diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (GPAT) genes from Schizochytrium sp. HX-308 were expressed in Yarrowia lipolytica to enhance lipid and EPA accumulation. In addition, engineering the enzyme activity of DGATs through protein engineering was found to be effective in enhancing lipid synthesis by replacing the conserved motifs "HFS" in ScDGAT2A and "FFG" in ScDGAT2B with the motif "YFP". Notably, combined with lipidomic analysis, the expression of ScDGAT2C and GPAT2 enhanced the storage of EPA in TG. Finally, the accumulation of lipid and EPA was further promoted by identifying and continuing to introduce the ScACC, ScACS, ScPDC, and ScG6PD genes from Schizochytrium sp., and the lipid and EPA titer of the final engineered strain reached 2.25 ± 0.03 g/L and 266.44 ± 5.74 mg/L, respectively, which increased by 174.39% (0.82 ± 0.02 g/L) and 282.27% (69.70 ± 0.80 mg/L) compared to the initial strain, respectively. CONCLUSION: This study shows that the expression of lipid synthesis genes from Schizochytrium sp. in Y. lipolytica effectively improves the synthesis of lipids and EPA, which provided a promising target for EPA-enriched microbial oil production.

2.
Chemosphere ; 352: 141442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346516

RESUMO

Most previous studies have focused primarily on the adverse effects of environmental chemicals on organisms of good healthy. Although global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached approximately 25%, the impact of environmentally persistent organic chemicals on organisms with NAFLD is substantially unknown. Polyhalogenated carbazoles (PHCZs) as emerging contaminants have been frequently detected in the environment and organisms. In this study, we investigated the impact of the most frequently detected PHCZs, 3,6-dichlorocarbazole (36-CCZ), on zebrafish with high-fat diet (HFD)-induced NAFLD. After 4 weeks exposure to environmentally relevant concentrations of 36-CCZ (0.16-0.45 µg/L), the accumulation of lipid in zebrafish liver dramatically increased, and the transcription of genes involved in lipid synthesis, transport and oxidation was significantly upregulated, demonstrating that 36-CCZ had exacerbated the NAFLD in zebrafish. Lipidomic analysis indicated that 36-CCZ had significantly affected liver lipid metabolic pathways, mainly including glycerolipids and glycerophospholipids. Additionally, fifteen lipids were identified as potential lipid biomarkers for 36-CCZ exacerbation of NAFLD, including diacylglycerols (DGs), triglycerides (TGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidic acid (PA), and phosphatidylinositol (PI). These findings demonstrate that long-term exposure to 36-CCZ can promote the progression of NAFLD, which will contribute to raising awareness of the health risks of PHCZs.


Assuntos
Carbazóis , Hepatopatia Gordurosa não Alcoólica , Perciformes , Animais , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Peixe-Zebra/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Triglicerídeos/metabolismo , Perciformes/metabolismo , Biomarcadores/metabolismo , Dieta Hiperlipídica
3.
Food Res Int ; 173(Pt 2): 113402, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803738

RESUMO

With the diversity of consumer demands for healthy food, stricter requirements have been put forward for the product quality of sea eel (Astroconger myriaster). From the common experience, remarkable differences could be observed between different parts of the sea eel. The textures, basic nutritional compositions, and lipid compositions from seven parts of sea eel were investigated to reach a comprehensive evaluation of the nutritional value. Sea eel was high-fat fish which contained 21.65% to 22.84% crude fat from part one to part seven. The seventh segment exhibited a lower moisture content (51.32%) and higher contents of protein (22.76%), ash (2.46%), carbohydrate (0.80%). The third and fourth parts remained higher hardness and good water-holding capacity. Sea eel had sixteen fatty acids, and the tail possessed a higher proportion of n - 3/n - 6 polyunsaturated fatty acids. Twenty-seven lipid species were determined in sea eel, and highly unsaturated fatty acids mainly stemmed from triglycerides, while saturated fatty acids mainly existed as diglycerides. Section six and seven were primarily diglycerides and monoglycerides. According to the characteristics of different parts, it can provide support for standardized segmentation of sea eel and quality control of different parts.


Assuntos
Diglicerídeos , Ácidos Graxos Ômega-3 , Animais , Lipidômica , Enguias , Valor Nutritivo , Ácidos Graxos Insaturados , Ácidos Graxos
4.
Food Res Int ; 172: 113147, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689910

RESUMO

Nowadays, plant-based milk consumption, as part of a healthy diet, is continuously increasing. In this paper, for the first time a lipidomic analysis on molecular species of triacylglycerol (TG) fraction of plant-based beverages (almond, soy, coconut) was performed by liquid chromatography quadrupole time-of-flight mass spectrometry. A total of 557 TG molecular species was measured, showing significantly different profiles between milk alternatives, compared with bovine milk. The most abundant TG molecular species were TG 18:1_18:1_18:1 and 18:1_18:1_18:2 for almond, TG 18:2_18:2_18:2 and 16:0_18:2_18:2 for soy, TG 12:0_10:0_12:0 and 12:0_12:0_14:0 for coconut. Unconventional fatty acids were detected in almond and soy. The main TG with ethereal linkage were TG-O 56:2, TG-O 56:4, and TG-O 56:5, while the main oxygenated TG was TG 54:5;1O. A total of 30 molecular species were identified as biomarkers for milk differentiation by principal component analysis, providing an interesting support for milk authentication and detection of adulteration on a larger sampling.


Assuntos
Leite , Prunus dulcis , Animais , Cocos , Lipidômica
5.
Front Physiol ; 14: 1244158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37772059

RESUMO

Glucosylceramides (GlcCer) are lipids that impact signaling pathways, serve as critical components of cellular membranes, and act as precursors for hundreds of other complex glycolipid species. Abnormal GlcCer metabolism is linked to many diseases, including cancers, diabetes, Gaucher disease, neurological disorders, and skin disorders. A key hurdle to fully understanding the role of GlcCer in disease is the development of methods to accurately detect and quantify these lipid species in a model organism. This will allow for the dissection of the role of this pool in vivo with a focus on all the individual types of GlcCer. In this review, we will discuss the analysis of the GlcCer population specifically in the nematode Caenorhabditis elegans, focusing on the mass spectrometry-based methods available for GlcCer quantification. We will also consider the combination of these approaches with genetic interrogation of GlcCer metabolic genes to define the biological role of these unique lipids. Furthermore, we will explore the implications and obstacles for future research.

6.
Int J Mol Sci ; 24(18)2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37762567

RESUMO

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. This study investigated 297 and 202 lipids in saliva and plasma samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (>2-fold, p < 0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes. Total triglycerides (TGs) increased (>2-3-fold) in plasma and saliva samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC for both sample types. A common ceramide species (d18:1/24:0) and phosphatidylinositol 38:4 decreased in both plasma and saliva by approximately two-fold. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. We identified 27 salivary and 10 plasma lipids as candidate markers for NSCLC through statistical evaluations. Moreover, this study highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Plasma , Ceramidas , Cromatografia Líquida de Alta Pressão , Triglicerídeos
7.
Eur J Cell Biol ; 102(3): 151337, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37392580

RESUMO

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides' fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest information on ceramide synthase inhibitors, their application in diseases including cancer therapy, and discuss approaches for drug discovery in the field of ceramide synthase inhibitors. We finally discussed strategies for developing strategies to use lipids and ceramides analysis in biological fluids for developing early biomarkers for cancer.


Assuntos
Ceramidas , Neoplasias , Humanos , Ceramidas/farmacologia , Apoptose , Autofagia
8.
Nutrients ; 15(14)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37513513

RESUMO

Combining exercise with fasting is known to boost fat mass-loss, but detailed analysis on the consequential mobilization of visceral and subcutaneous WAT-derived fatty acids has not been performed. In this study, a subset of fasted male rats (66 h) was submitted to daily bouts of mild exercise. Subsequently, by using gas chromatography-flame ionization detection, the content of 22 fatty acids (FA) in visceral (v) versus subcutaneous (sc) white adipose tissue (WAT) depots was compared to those found in response to the separate events. Findings were related to those obtained in serum and liver samples, the latter taking up FA to increase gluconeogenesis and ketogenesis. Each separate intervention reduced scWAT FA content, associated with increased levels of adipose triglyceride lipase (ATGL) protein despite unaltered AMP-activated protein kinase (AMPK) Thr172 phosphorylation, known to induce ATGL expression. The mobility of FAs from vWAT during fasting was absent with the exception of the MUFA 16:1 n-7 and only induced by combining fasting with exercise which was accompanied with reduced hormone sensitive lipase (HSL) Ser563 and increased Ser565 phosphorylation, whereas ATGL protein levels were elevated during fasting in association with the persistently increased phosphorylation of AMPK at Thr172 both during fasting and in response to the combined intervention. As expected, liver FA content increased during fasting, and was not further affected by exercise, despite additional FA release from vWAT in this condition, underlining increased hepatic FA metabolism. Both fasting and its combination with exercise showed preferential hepatic metabolism of the prominent saturated FAs C:16 and C:18 compared to the unsaturated FAs 18:1 n-9 and 18:2 n-6:1. In conclusion, depot-specific differences in WAT fatty acid molecule release during fasting, irrelevant to their degree of saturation or chain length, are mitigated when combined with exercise, to provide fuel to surrounding organs such as the liver which is correlated with increased ATGL/ HSL ratios, involving AMPK only in vWAT.


Assuntos
Ácidos Graxos , Esterol Esterase , Ratos , Masculino , Animais , Esterol Esterase/metabolismo , Ácidos Graxos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Lipase/metabolismo , Lipólise/fisiologia , Obesidade/metabolismo , Jejum/metabolismo , Tecido Adiposo/metabolismo
9.
Therap Adv Gastroenterol ; 16: 17562848231168199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153496

RESUMO

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported. Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment. Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116). Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model. Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers. Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

10.
Biomed Pharmacother ; 162: 114719, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37080088

RESUMO

Cistanche deserticola Y. C. Ma (CD), known as "desert ginseng", has been found to have hepatoprotective effect. This research aimed to investigate the quality control and its alleviating effect on alcoholic liver injury in mice. In this study, for the first time, a sensitive and efficient ultra-high-performance liquid chromatography with quadrupole ion-trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed to rapidly characterize nine representative phenylethanoid glycosides (PhGs) in the CD extract within 14 min, offering a reference for the quality control standard of this plant. In addition, we found that the CD extract significantly inhibited the weight loss, decreased the liver index, and attenuated excessive lipid deposition, inflammatory and oxidative stress in the mice liver. With the help of the high-throughput lipidomics technique, we discovered that CD markedly reversed 17 lipid metabolites and their involved linoleic acid, arachidonic acid and glycerophospholipid metabolic pathways. As these metabolites are mainly associated with lipid metabolism and liver damage, we further used molecular biological tests to found that CD could regulate the upstream genes and proteins of the lipid metabolism pathway, including adenosine 5'-monophosphate-activated protein kinase (AMPK), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxidase proliferators activate receptors α (PPARα). In conclusion, this study elucidates the modulatory effects of CD on lipid metabolism disorders in alcoholic fatty liver from holistic system and provides a reference for further research and development of CD as a therapeutic agent.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Cistanche , Medicamentos de Ervas Chinesas , Camundongos , Animais , Cistanche/química , Etanol , Medicamentos de Ervas Chinesas/química , Fígado/metabolismo , Lipídeos
11.
Metabolites ; 13(4)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37110211

RESUMO

This cross-sectional study aimed to investigate differences in skin surface lipids (SSL) and explore related metabolic pathways among females of different ages in Henan Province. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to determine the lipid composition of the skin surface of 58 female volunteers who were divided into three age groups. Statistical analysis was performed using Progenesis QI, Ezinfo, and MetaboAnalyst. Multivariate and enrichment analysis were used to identify the different SSL among the groups. A total of 530 lipid entities were identified and classified into eight classes. Among these, 63 lipids were significantly different between the groups. Lower levels of glycerolipids (GLs) and sphingolipids (SPs) were observed in the middle-aged group, while higher levels of GLs were found in the elder group. GLs belonged to the largest and statistically significant enrichment of lipid metabolic pathways, and the lipid individuals enriched to the sphingoid bases metabolism were the most and statistically significant. These findings suggest that there are differences in hand SSL among females of different ages, which may be related to GLs and sphingoid bases metabolism.

12.
Diabetes Ther ; 14(3): 553-567, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36732434

RESUMO

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in type 1 diabetes (T1D). However, there is a need for daily practice tools for identifying those more prone to suffer from these events. We aimed to assess the relationships between nuclear magnetic resonance (1H NMR)-based lipidomic analysis and several CVD risk variables (including preclinical carotid atherosclerosis) in individuals with T1D at high risk. METHODS: We included patients with T1D without CVD, with at least one of the following: age ≥ 40 years, diabetic kidney disease, or ≥ 10 years of evolution with another risk factor. The presence of plaque (intima-media thickness > 1.5 mm) was determined by standardized ultrasonography protocol. Lipidomic analysis was performed by 1H NMR. Bivariate and multivariate-adjusted differences in 1H NMR lipidomics were evaluated. RESULTS: We included n = 131 participants (49.6% female, age 46.4 ± 10.3 years, diabetes duration 27.0 ± 9.5 years, 47.3% on statins). Carotid plaques were present in 28.2% of the individuals (n = 12, with ≥ 3 plaques). Glucose (HbA1c), anthropometric (body mass index and waist circumference), and insulin resistance-related (fatty liver index and estimated glucose disposal rate) variables were those most associated with 1H NMR-derived lipidomic analysis (p < 0.01 for all). Regarding preclinical atherosclerosis, sphingomyelin was independently associated with carotid plaque presence (for 0.1 mmol/L increase, OR 0.50 [0.28-0.86]; p = 0.013), even after adjusting for age, sex, hypertension, statin use, mean 5-year HbA1c and diabetes duration. Furthermore, linoleic acid and ω-6 fatty acids remained independently associated with higher plaque burden (≥ 3 plaques) in multivariate models (0.17 [0.03-0.93] and 0.27 [0.07-0.97], respectively; p < 0.05 for both). CONCLUSION: In our preliminary study of individuals with T1D at high risk, several 1H NMR-derived lipidomic parameters were independently associated with preclinical atherosclerosis. Specifically, ω-6 fatty acids and linoleic acid seem promising for identifying those with higher plaque burden.

13.
J Lipid Res ; 64(3): 100343, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36773847

RESUMO

Evaluating lipid profiles in human tissues and biofluids is critical in identifying lipid metabolites in dysregulated metabolic pathways. Due to various chemical characteristics, single-run lipid analysis has not yet been documented. Such approach is essential for analyzing pathology-related lipid metabolites. Age-related macular degeneration, the leading cause of vision loss in western countries, is emblematic of this limitation. Several studies have identified alterations in individual lipids but the majority are based on targeted approaches. In this study, we analyzed and identified approximately 500 lipid species in human biofluids (plasma and erythrocytes) and ocular tissues (retina and retinal pigment epithelium) using the complementarity of hydrophilic interaction liquid chromatography (HILIC) and reversed-phase chromatography (RPC), coupled to high-resolution mass spectrometry. For that, lipids were extracted from human eye globes and blood from 10 subjects and lipidomic analysis was carried out through analysis in HILIC and RPC, alternately. Furthermore, we illustrate the advantages and disadvantages of both techniques for lipid characterization. RPC showed greater sensitivity in hydrophobicity-based lipid separation, detecting diglycerides, triglycerides, cholesterol, and cholesteryl esters, whereas no signal of these molecules was obtained in HILIC. However, due to coelution, RPC was less effective in separating polar lipids like phospholipids, which were separated effectively in HILIC in both ionization modes. The complementary nature of these analytical approaches was essential for the detection and identification of lipid classes/subclasses, which can then provide distinct insights into lipid metabolism, a determinant of the pathophysiology of several diseases involving lipids, notably age-related macular degeneration.


Assuntos
Lipidômica , Degeneração Macular , Humanos , Lipidômica/métodos , Espectrometria de Massas/métodos , Cromatografia Líquida/métodos , Fosfolipídeos
14.
Food Chem ; 398: 133880, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35986997

RESUMO

A jeotgal-like product was processed from Chinook salmon (Oncorrhynchus tshawytscha) roe. Physicochemical, biochemical, and microbiological compositions were studied during 30 days of fermentation. Fermentation decreased water activity (aw) and pH value. Total bacterial and LAB counts (log CFU/g) increased up to 12 days of processing and then no further changes occurred. Saturated fatty acids (SFA) decreased (p < 0.05), monounsaturated fatty acids (MUFA) did not change (p > 0.05), whereas fermentation time improved polyunsaturated fatty acids (PUFA) content significantly (p < 0.05). Astaxanthin, lutein and phospholipids (PC, LPC, PE, LPE and LPS) concentrations were found to increase, while cholesterol and tocopherol contents were decreased at the end of the fermentation (p < 0.05). This study indicates that the nutritional value of salmon roe can be enhanced by fermentation.


Assuntos
Ácidos Graxos , Salmão , Animais , Colesterol , Ácidos Graxos Monoinsaturados , Ácidos Graxos Insaturados
15.
mBio ; 13(6): e0229722, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36445081

RESUMO

Grass carp is an important commercial fish in China that is plagued by various diseases, especially the hemorrhagic disease induced by grass carp reovirus (GCRV). Nevertheless, the mechanism by which GCRV hijacks the host metabolism to complete its life cycle is unclear. In this study, we performed lipidomic analysis of grass carp liver samples collected before and after GCRV infection. GCRV infection altered host lipid metabolism and increased de novo fatty acid synthesis. Increased de novo fatty acid synthesis induced accumulation of lipid droplets (LDs). LDs are associated with GCRV viroplasms, as well as viral proteins and double-stranded RNA. Pharmacological inhibition of LD formation led to the disappearance of viroplasms, accompanied by decreased viral replication capacity. Moreover, transmission electron microscopy revealed LDs in close association with the viroplasms and mounted GCRV particles. Collectively, these data suggest that LDs are essential for viroplasm formation and are sites for GCRV replication and assembly. Our results revealed the detailed molecular events of GCRV hijacking host lipid metabolism to benefit its replication and assembly, which may provide new perspective for the prevention and control of GCRV. IMPORTANCE Grass carp reovirus (GCRV) is the most virulent pathogen in the genus Aquareovirus, which belongs to the family Reoviridae. GCRV-induced hemorrhagic disease is a major threat to the grass carp aquaculture industry. Viruses are obligate intracellular parasites that require host cell machinery to complete their life cycle; the mechanism by which GCRV hijacks the host metabolism to benefit viral replication and assembly remains unclear. Our study demonstrated that GCRV infection alters host lipid metabolism and increases de novo fatty acid synthesis. The increased de novo fatty acid synthesis induced accumulation of LDs, which act as sites or scaffolds for GCRV replication and assembly. Our findings illustrate a typical example of how the virus hijacks cellular organelles for replication and assembly and hence may provide new insights for the prevention and control of GCRV.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Reoviridae , Reoviridae , Animais , Gotículas Lipídicas , Reoviridae/fisiologia , Infecções por Reoviridae/genética , Ácidos Graxos
17.
Hypertension ; 79(10): 2274-2287, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35993233

RESUMO

BACKGROUND: Systemic inflammation caused by dysfunctional macrophages is a crucial pathogenetic event in preeclampsia (PE). Trophoblast-derived extracellular vesicles (T-EVs) are potent immune cell signaling modulators in pregnancy. Herein, we aimed to investigate T-EVs' effect and mechanism on macrophage polarization and its role in PE pathogenesis, which remain unclear. METHODS: Flow cytometry and immunochemistry were used to determine placental macrophage phenotypes. T-EVs were immuno-isolated via placental alkaline phosphatase antibody and identified by transmission electron microscopy and nanoparticle tracking analysis. Quantitative real-time polymerase chain reaction and flow cytometry were used to examine the effects of T-EVs on macrophage polarization, and correlation analysis of T-EVs lipidomics and macrophages transcriptome were performed to explore how T-EVs modulate macrophages. Animal experiments were established to investigate the relationship among PE, T-EVs, and macrophages. RESULTS: Macrophages shift from the M2 to M1 phenotype in the preeclamptic placenta. Also, T-EVs from women with PE (PE-EVs) significantly upregulated M1 gene markers and significantly downregulated CD163 expression in macrophages compared with T-EVs in women with normal pregnancies (NP-EVs). Mechanistically, correlation analysis with T-EVs lipidome and the transcriptome of macrophages treated with PE-EVs or NP-EVs indicated that 37 lipids altered in PE-EVs considerably affected classical inflammatory biological pathways in macrophages. Finally, animal experiments revealed that PE-EVs triggered PE-like symptoms in pregnant mice, which were alleviated after macrophage depletion. CONCLUSIONS: T-EVs from women with PE could promote preeclampsia by inducing macrophage imbalance polarization, signifying a potential novel interventional target for the prevention and management of PE.


Assuntos
Vesículas Extracelulares , Pré-Eclâmpsia , Animais , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Macrófagos/metabolismo , Camundongos , Placenta/metabolismo , Gravidez , Trofoblastos/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-35819473

RESUMO

BACKGROUND: Occult hypoperfusion describes the absence of sufficient microcirculation despite normal vital signs. It is known to be associated with prolonged elevation of serum lactate and later complications in severely injured patients. We hypothesized that changes in circulating lipids are related to responsiveness to resuscitation. The purpose of this study is investigating the relation between responsiveness to resuscitation and lipidomic course after poly trauma. METHODS: Twenty-five male pigs were exposed a combined injury of blunt chest trauma, liver laceration, controlled haemorrhagic shock, and femoral shaft fracture. After 1 h, animals received resuscitation and fracture stabilization. Venous blood was taken regularly and 233 specific lipids were analysed. Animals were divided into two groups based on serum lactate level at the end point as an indicator of responsiveness to resuscitation (<2 mmol/L: responder group (R group), ≧2 mmol/L: occult hypoperfusion group (OH group)). RESULTS: Eighteen animals met criteria for the R group, four animals for the OH group, and three animals died. Acylcarnitines showed a significant increase at 1 h compared to baseline in both groups. Six lipid subgroups showed a significant increase only in R group at 2 h. There was no significant change at other time points. CONCLUSIONS: Six lipid groups increased significantly only in the R group at 2 h, which may support the idea that they could serve as potential biomarkers to help us to detect the presence of occult hypoperfusion and insufficient resuscitation. We feel that further study is required to confirm the role and mechanism of lipid changes after trauma.

19.
Prostaglandins Other Lipid Mediat ; 162: 106651, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35680078

RESUMO

Cystinuria is a genetic disorder of cystine transport, including defective protein b0,+AT (encoded by SLC7A9), and/or rBAT (encoded by SLC3A1). Patients present hyperexcretion of cystine in the urine, recurrent cystine lithiasis, and progressive decline in kidney function. Moreover, heterodimer transport is defective. To date, little omics data are accessible regarding this metabolic disease caused by membrane proteins. Since membrane function is closely related to changes in the lipidome, we decided to explore the changes in kidney tissue of a self-established cystinuria rat model by performing lipidomic analysis by LC-MS/MS. Our results demonstrated that Slc7a9 deficiency changed the lipid profile of the renal cortex and induced vital modifications in the lipidome, including major alterations in ChE, LPA, and PA. Among those alterations, this lipidomic study highlights the lipid changes that participate in inflammatory responses during cystinuria. As a result, lipid research, perhaps has great potential, for it may lead to the identification of novel therapeutic targets for the prevention and treatment of cystinuria.


Assuntos
Cistinúria , Sistemas de Transporte de Aminoácidos Básicos/genética , Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Animais , Cromatografia Líquida , Cistina/metabolismo , Cistinúria/genética , Cistinúria/metabolismo , Rim/metabolismo , Metabolismo dos Lipídeos , Lipidômica , Lipídeos , Ratos , Espectrometria de Massas em Tandem
20.
Food Res Int ; 156: 111199, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35651051

RESUMO

This study evaluated the protective effect of parsley (Petroselinum crispum Mill.) against lipid and cholesterol oxidation in omelets prepared by air frying, pan frying, and microwaving. The bioactive composition and in vitro antioxidant capacity of parsley extract was characterized. Compounds such as phenolic acids and their derivatives (p-coumaric acid, p-coumaric acid 4-O-hexoside) and flavonoids (apigenin 7-glucoside, quercetin-O-pentosyl-hexoside) were identified in parsley by UHPLC-ESI-MS. Moreover, the presence of these bioactive constituents was investigated in omelets. Cooking induced lipid oxidation and increased the level of cholesterol oxidation products (COPs) in control omelets, which was more pronounced after air frying and microwaving. The total content of COPs increased from 40.69 ± 2.26 µg/g (raw) to 821.05 ± 13.77 µg/g (air frying), 805.21 ± 14.50 µg/g (microwaving), and 311.07 ± 13.84 µg/g (pan frying). The addition of parsley proved to be effective reducing COPs formation, mainly in air-fried samples with 0.75% parsley (81.73% of protection). Chromatographic analyses revealed the thermo-degradation of parsley compounds, since only two flavonoids detected in parsley were found in omelets containing the herb after cooking. Nonetheless, these findings indicate the potential application of parsley as a natural inhibitor of cholesterol and lipid oxidation in food systems such as omelets.


Assuntos
Antioxidantes , Petroselinum , Antioxidantes/química , Colesterol/química , Flavonoides , Oxirredução
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