Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Methods for Oxygen Determination in an NMR Bioreactor as a Surrogate Marker for Metabolomic Studies in Living Cell Cultures

Tue, 21/11/2023 - 12:00
Anal Chem. 2023 Nov 21. doi: 10.1021/acs.analchem.3c02314. Online ahead of print.ABSTRACTNuclear magnetic resonance (NMR) approaches have been described as a powerful method for measuring oxygen in tissue cultures and body fluids by using relaxation time dependencies of substances on pO2. The present NMR study describes methods to longitudinally monitor global, in situ intracellular, and spatially resolved oxygen tension in culture media and 3D cell cultures using relaxation times of water without the need to use external sensors. 1H NMR measurements of water using a modified inversion recovery pulse scheme were employed for global, i.e., intra- and extracellular oxygen estimation in an NMR-bioreactor. The combination of 1H relaxation time T1 and diffusion measurements of water was employed for in situ cellular oxygen content determination. Spatially selective water relaxation time estimations were used for spatially resolved oxygen quantification along the NMR tube length. The inclusion in a study protocol of the presented techniques for oxygen quantification, as a surrogate marker of oxidative phosphorylation (OXPHOS), provides the possibility to measure mitochondrial respiration and metabolic changes simultaneously.PMID:37989262 | DOI:10.1021/acs.analchem.3c02314

High-Throughput f-LAESI-IMS-MS for Mapping Biological Nitrogen Fixation One Cell at a Time

Tue, 21/11/2023 - 12:00
Anal Chem. 2023 Nov 21. doi: 10.1021/acs.analchem.3c03651. Online ahead of print.ABSTRACTFor the characterization of the metabolic heterogeneity of cell populations, high-throughput single-cell analysis platforms are needed. In this study, we utilized mass spectrometry (MS) enhanced with ion mobility separation (IMS) and coupled with an automated sampling platform, fiber-based laser ablation electrospray ionization (f-LAESI), for in situ high-throughput single-cell metabolomics in soybean (Glycine max) root nodules. By fully automating the in situ sampling platform, an overall sampling rate of 804 cells/h was achieved for high numbers (>500) of tissue-embedded plant cells. This is an improvement by a factor of 13 compared to the previous f-LAESI-MS configuration. By introducing IMS, the molecular coverage improved, and structural isomers were separated on a millisecond time scale. The enhanced f-LAESI-IMS-MS platform produced 259 sample-related peaks/cell, almost twice as much as the 131 sample-related peaks/cell produced by f-LAESI-MS without IMS. Using the upgraded system, two types of metabolic heterogeneity characterization methods became possible. For unimodal metabolite abundance distributions, the metabolic noise reported on the metabolite level variations within the cell population. For bimodal distributions, the presence of metabolically distinct subpopulations was established. Discovering these latent cellular phenotypes could be linked to the presence of different cell states, e.g., proliferating bacteria in partially occupied plant cells and quiescent bacteroids in fully occupied cells in biological nitrogen fixation, or spatial heterogeneity due to altered local environments.PMID:37989253 | DOI:10.1021/acs.analchem.3c03651

Childhood socioeconomic position and sex-specific trajectories of metabolic traits across early life: prospective cohort study

Tue, 21/11/2023 - 12:00
EBioMedicine. 2023 Nov 20;98:104884. doi: 10.1016/j.ebiom.2023.104884. Online ahead of print.ABSTRACTBACKGROUND: Socioeconomic inequalities in cardiovascular disease risk begin early in life and are more pronounced in females than males later in life. Causal atherogenic traits explaining this are not well understood. We explored sex-specific associations between childhood socioeconomic position (SEP) and molecular measures of systemic metabolism across early life.METHODS: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort in southwest England. Pregnant women with an expected delivery date between 1991 and 1992 were invited to participate. Maternal education was the primary indicator of SEP. Concentrations of 148 metabolic traits from targeted metabolomics (nuclear magnetic resonance spectroscopy) from research clinics at ages 7, 15, 18 and 25 years were analysed. The sex-specific slope index of inequality (SII) in trajectories of metabolic traits was estimated using multilevel models.FINDINGS: Total number of participants included was 6537 (12,543 repeated measures). Lower maternal education was associated with more adverse levels of several atherogenic lipids and key metabolic traits among females at age 7 years, but not males. For instance, SII for very small very-low-density lipoprotein (VLDL) concentrations was 0.16SD (95% CI: 0.01, 0.30) among females and -0.02SD (95% CI: -0.16, 0.13) among males. Between 7 and 25 years, inequalities widened among females and emerged among males particularly for VLDL particle concentrations, apolipoprotein-B concentrations, and inflammatory glycoprotein acetyls. For instance, at 25 years, SII for very small VLDL concentrations was 0.36SD (95% CI: 0.20, 0.52) and 0.22SD (95% CI: 0.04, 0.40) among females and males respectively.INTERPRETATION: Prevention of socioeconomic inequalities in cardiovascular disease risk requires a life course approach beginning at the earliest opportunity, especially among females.FUNDING: The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). KON is supported by a Health Research Board (HRB) of Ireland Investigator Led Award (ILP-PHR-2022-008). JB, GDS and KT work in a unit funded by the UK MRC (MC_UU_00011/1 and MC UU 00011/3) and the University of Bristol. OR is supported by a UKRI Future Leaders Fellowship (MR/S03532X/1). These funding sources had no role in the design and conduct of this study. This publication is the work of the authors and KON will serve as guarantor for the contents of this paper.PMID:37989036 | DOI:10.1016/j.ebiom.2023.104884

Neurotoxicity of the Cu(OH)<sub>2</sub> Nanopesticide through Perturbing Multiple Neurotransmitter Pathways in Developing Zebrafish

Tue, 21/11/2023 - 12:00
Environ Sci Technol. 2023 Nov 21. doi: 10.1021/acs.est.3c06284. Online ahead of print.ABSTRACTThe copper hydroxide [Cu(OH)2] nanopesticide is an emerging agricultural chemical that can negatively impact aquatic organisms. This study evaluated the behavioral changes of zebrafish larvae exposed to the Cu(OH)2 nanopesticide and assessed its potential to induce neurotoxicity. Metabolomic and transcriptomic profiling was also conducted to uncover the molecular mechanisms related to potential neurotoxicity. The Cu(OH)2 nanopesticide at 100 μg/L induced zebrafish hypoactivity, dark avoidance, and response to the light stimulus, suggestive of neurotoxic effects. Altered neurotransmitter-related pathways (serotoninergic, dopaminergic, glutamatergic, GABAergic) and reduction of serotonin (5-HT), dopamine (DA), glutamate (GLU), γ-aminobutyric acid (GABA), and several of their precursors and metabolites were noted following metabolomic and transcriptomic analyses. Differentially expressed genes (DEGs) were associated with the synthesis, transport, receptor binding, and metabolism of 5-HT, DA, GLU, and GABA. Transcripts (or protein levels) related to neurotransmitter receptors for 5-HT, DA, GLU, and GABA and enzymes for the synthesis of GLU and GABA were downregulated. Effects on both the glutamatergic and GABAergic pathways in zebrafish were specific to the nanopesticide and differed from those in fish exposed to copper ions. Taken together, the Cu(OH)2 nanopesticide induced developmental neurotoxicity in zebrafish by inhibiting several neurotransmitter-related pathways. This study presented a model for Cu(OH)2 nanopesticide-induced neurotoxicity in developing zebrafish that can inform ecological risk assessments.PMID:37988762 | DOI:10.1021/acs.est.3c06284

A Novel mechanism of herbicide action through disruption of pyrimidine biosynthesis

Tue, 21/11/2023 - 12:00
Proc Natl Acad Sci U S A. 2023 Nov 28;120(48):e2313197120. doi: 10.1073/pnas.2313197120. Epub 2023 Nov 21.ABSTRACTA lead aryl pyrrolidinone anilide identified using high-throughput in vivo screening was optimized for efficacy, crop safety, and weed spectrum, resulting in tetflupyrolimet. Known modes of action were ruled out through in vitro enzyme and in vivo plant-based assays. Genomic sequencing of aryl pyrrolidinone anilide-resistant Arabidopsis thaliana progeny combined with nutrient reversal experiments and metabolomic analyses confirmed that the molecular target of the chemistry was dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the fourth step in the de novo pyrimidine biosynthesis pathway. In vitro enzymatic and biophysical assays and a cocrystal structure with purified recombinant plant DHODH further confirmed this enzyme as the target site of this class of chemistry. Like known inhibitors of other DHODH orthologs, these molecules occupy the membrane-adjacent binding site of the electron acceptor ubiquinone. Identification of a new herbicidal chemical scaffold paired with a novel mode of action, the first such finding in over three decades, represents an important leap in combatting weed resistance and feeding a growing worldwide population.PMID:37988466 | DOI:10.1073/pnas.2313197120

Metabolomics, the future of biomarkers?

Tue, 21/11/2023 - 12:00
Eur J Emerg Med. 2023 Nov 21. doi: 10.1097/MEJ.0000000000001097. Online ahead of print.NO ABSTRACTPMID:37988452 | DOI:10.1097/MEJ.0000000000001097

Assessing the causal association between human blood metabolites and the risk of gout

Tue, 21/11/2023 - 12:00
Eur J Clin Invest. 2023 Nov 21:e14129. doi: 10.1111/eci.14129. Online ahead of print.ABSTRACTBACKGROUND: The occurrence of gout is closely related to metabolism, but there is still a lack of evidence on the causal role of metabolites in promoting or preventing gout.METHODS: We applied a two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and gout using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. We also performed a metabolic pathway analysis to identify potential metabolic pathways.RESULTS: After screening, 486 metabolites were retained for MR analysis. After screening by IVW and sensitivity analysis, 14 metabolites were identified with causal effect on gout (P < 0.05), among which hexadecanedioate was the most significant candidate metabolite associated with a lower risk of gout (IVW OR = 0.50; 95% CI = 0.38-0.67; P = 1.65 × 10-6 ). Metabolic pathway analysis identified one pathway that may be associated with the disease.CONCLUSION: This MR study combining genomics with metabolomics provides a novel insight into the causal role of blood metabolites in the risk of gout, which implies that examination of certain blood metabolites would be a feasible strategy for screening populations with a higher risk of gout.PMID:37988199 | DOI:10.1111/eci.14129

A Simple, Rapid, and Effective Heparinase Protocol to Enable Nucleic Acid Study from Frozen Heparinized Plasma

Tue, 21/11/2023 - 12:00
Methods Protoc. 2023 Nov 20;6(6):112. doi: 10.3390/mps6060112.ABSTRACTCell-free RNAs (cfRNAs) are promising analytes as non-invasive biomarkers and have even greater potential if tied in with metabolomics. Plasma is an optimal source for cfRNAs but is often derived from a variety of anticoagulants. Plasma obtained in heparin is suitable for metabolomics but is difficult to utilize for qPCR-based downstream analysis. In the present study, we aimed to develop a simple, time-efficient, and cost-effective heparinase protocol, followed by library preparation and sequencing of human plasma cfRNAs drawn and stored in heparin at -80 °C for several years. Blood was collected in CPT™ sodium heparin tubes from patients with chronic HCV infection (NCT02400216) at the National Institutes of Health (NIH) Clinical Center. Plasma cfRNAs were treated with heparinase I and used for library preparation and next-generation sequencing (NGS). Heparinase treatment maintained RNA integrity and allowed for successful library preparation for all the study subjects even with 7 ng of cfRNAs as starting material. The classification report derived from Pavian R package v1.2.0 showed no artificial reads. The abundance of chordate over microbial reads suggests no addition of experimental error through heparinase I treatment. We report a novel and practical approach to heparinase treatment for human plasma collected and frozen in sodium heparin for several years. This is an effective demonstration of utilizing heparin plasma for NGS and downstream transcriptomic research, which could then be integrated with metabolomics from the same samples, maximizing efficiency and minimizing blood draws.PMID:37987359 | DOI:10.3390/mps6060112

Frontiers in NMR metabolomics

Tue, 21/11/2023 - 12:00
Magn Reson Chem. 2023 Dec;61(12):627. doi: 10.1002/mrc.5400.NO ABSTRACTPMID:37987217 | DOI:10.1002/mrc.5400

NMR metabolomic modelling of age and lifespan: a multi-cohort analysis

Tue, 21/11/2023 - 12:00
medRxiv. 2023 Nov 8:2023.11.07.23298200. doi: 10.1101/2023.11.07.23298200. Preprint.ABSTRACTMetabolomic age models have been proposed for the study of biological aging, however they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. 98 metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈ 31,000 individuals, age range 24-86 years). We used non-linear and penalised regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with ageing risk factors and phenotypes. Within the UK Biobank (N≈ 102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, chronic obstructive pulmonary disease) and all-cause mortality. Cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47-0.65 in the training set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with chronological age were modest ( r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06 / metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.PMID:37986811 | PMC:PMC10659522 | DOI:10.1101/2023.11.07.23298200

Widely targeted metabolic profiling provides insights into variations in bioactive compounds and antioxidant activity of sesame, soybean, peanut, and perilla

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113586. doi: 10.1016/j.foodres.2023.113586. Epub 2023 Oct 14.ABSTRACTOilseeds are important sources of diversified nutraceuticals with marked health attributes. Thus, a better understanding of metabolome differences between common oilseeds will be conducive to the food pharmacy. This study aimed to compare the metabolite profiles and antioxidant activity of sesame, soybean, peanut, and perilla seeds and reveal the variation in bioactive compounds. LC-MS-based widely targeted metabolic profiling identified a total of 975 metabolites, of which 753 were common to the four crops. Multivariate analyses unveiled a crop-specific accumulation of metabolites, with 298-388 DAMs (differentially accumulated metabolites) identified. Amino acid metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis, and lipid metabolism were the most differentially regulated pathways. Furthermore, we revealed the variation in the relative content of 48, 20, 18, 9, 18, 11, and 6 differentially accumulated bioactive flavonoids, phenolic acids, amino acids, vitamins, terpenoids, alkaloids, and coumarins, respectively. Most of the flavonoids accumulated highly in soybean, followed by perilla. Sesame exhibited a better amino acid profile than other oilseeds. DPPH and FRAP assays showed that the antioxidant activity of perilla seed extracts was the highest, followed by soybean, peanut, and sesame. Our results provide data support for the comprehensive use of sesame, perilla, soybean, and peanut seeds in food, and pharmaceutical industries.PMID:37986527 | DOI:10.1016/j.foodres.2023.113586

Untargeted metabolomics provide new insights into the implication of Lactobacillus helveticus strains isolated from natural whey starter in methylglyoxal-mediated browning

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113644. doi: 10.1016/j.foodres.2023.113644. Epub 2023 Oct 26.ABSTRACTHard cheeses may occasionally show a brown discolouration during ripening due to multifactorial phenomena that involve bacteria and give rise to pyrazines arising from methylglyoxal. The present work aimed at developing a novel approach to investigate the role of natural starters in browning. To this object, 11 strains of L. helveticus were incubated in a medium containing 10 % rennet casein dissolved in whey, and then growth was monitored by measuring pH and number of genomes/mL. Browning was assessed through CIELab analysis, methylglyoxal production was determined by targeted mass spectrometry, and untargeted metabolomics was used to extrapolate marker compounds associated with browning discoloration. The medium allowed the growth of all the strains tested and differences in colour were observed, especially for strain A7 (ΔE* value 15.92 ± 0.27). Noteworthy, this strain was also the higher producer of methylglyoxal (2.44 µg/mL). Metabolomics highlighted pyrazines and β-carboline compounds as markers of browning at 42 °C and 16 °C, respectively. Moreover, multivariate statistics pointed out differences in free amino acids and oligopeptides linked to proteolysis, while 1,2-propanediol and S-Lactoylglutathione suggested specific detoxification route in methylglyoxal-producing strains. Our model allowed detecting differences in browning amid strains, paving the way towards the study of individual L. helveticus strains to identify the variables leading to discoloration or to study the interaction between different strains in natural whey starters.PMID:37986486 | DOI:10.1016/j.foodres.2023.113644

Impact of storage time on non-volatile metabolites and fungal communities in Liupao tea using LC-MS based non-targeted metabolomics and high-throughput sequencing

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113615. doi: 10.1016/j.foodres.2023.113615. Epub 2023 Oct 25.ABSTRACTLong-term storage of Liupao tea (LPT) is usually believed to enhance its quality and commercial value. The non-volatile metabolites variations and the fungal succession play a key role for organoleptic qualities during the storage procedure. To gain in-depth understanding the impact of storage time on the quality of LPT, two different brands of LPT with different storage time, including Maosheng LPTs (MS) with 0, 5, 10 and 15 years and Tianyu LPTs (TY) with 0, 3, 5, 8 and 10 years, were resorted to investigate the changes of non-volatile metabolites and fungi as well as their correlation by multi-omics. A total of 154 and 119 differential metabolites were identified in these two different brands of MS and TY, respectively, with the aid of high-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry. In both categories of LPTs, the transformation of differential metabolites in the various stages referred to the formation of alkaloids, increase of organic acids, biosynthesis of terpenoids as well as glycosylation and methylation of flavonoids. Thereinto, glycosylation and methylation of flavonoids were the critical stages for distinguishing MS and TY, which were discovered in MS and TY stored for about 10 and 8 years, respectively. Moreover, the results of high-throughput sequencing showed that the key fungal genera in the storage of LPTs consisted of Eurotium, Aspergillus, Blastobotrys, Talaromyces, Thermomyces and Trichomonascus. It was confirmed on the basis of multivariate analysis that the specific fungal genera promoted the transformation of metabolites, affecting the tea quality to some extent. Therefore, this study provided a theoretical basis for the process optimization of LPT storage.PMID:37986470 | DOI:10.1016/j.foodres.2023.113615

Metabolomic and transcriptomic integrated analysis revealed the decrease of monoterpenes accumulation in table grapes during long time low temperature storage

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113601. doi: 10.1016/j.foodres.2023.113601. Epub 2023 Oct 14.ABSTRACTLow temperature is the commonly used technique for maintaining the quality of table grapes during postharvest storage. However, this technique could strongly affect the aromatic flavor of fruit. Monoterpenes are the key compounds contributing to the Muscat aromas of grapes. The detailed information and molecular mechanisms underlying the changes in monoterpenes during postharvest low temperature storage have not been thoroughly characterized. In this study, the effects of low temperature storage on the free and bound monoterpene profiles in four cultivars of table grape were determined at both the transcriptomic and metabolomic levels. A total of 27 compounds in both free and bound forms were identified in the four cultivars and showed quantitative differences between the cultivars. Hierarchical cluster and principal component analysis indicated that the free and bound monoterpene profiles were remarkably affected by the low temperature storage. The monoterpenes in the same biosynthesis pathway were clustered together and showed similar evolution trends during low temperature storage. And the content of most of free monoterpenes underwent a rapid decline during low-temperature storage at a certain stage, but the time was different in 4 grape cultivars. Transcriptomic analysis revealed that the expression of DXS, HDR, GPPS and TPS genes involved in the monoterpene synthesis pathway were consistent with the changes in the accumulation of monoterpene compounds. While the expression of HMGS, HMGR genes in MVA pathway and branch genes GGPPS and FPPS were negatively correlated with the accumulation of monoterpenes. The findings provide new insights into the underlying mechanisms of the berry aroma flavor change during low temperature storage.PMID:37986463 | DOI:10.1016/j.foodres.2023.113601

Unveiling targeted spatial metabolome of rice seed at the dough stage using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry imaging

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113578. doi: 10.1016/j.foodres.2023.113578. Epub 2023 Oct 10.ABSTRACTRice (Oryza sativa) seeds contain a variety of metabolites, which not only provide energy for their own growth and development, but also are an important source of nutrition for humans. It is crucial to study the distribution of metabolites in rice seeds, but the spatial metabolome of rice seeds is rarely investigated. In this study, Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) imaging was used to reveal the spatial distribution of free soluble sugars (glucose, fructose, sucrose, and maltose), amino acids (9 essential amino acids and 2 amino acids affecting rice eating quality: L-aspartic acid and L-glutamic acid), and 4 metabolites in the flavonoids synthesis pathway (cinnamic acid, naringenin chalcone, naringenin, and dihydrokaempferol) in rice seed at the dough stage. It was found that the 4 free soluble sugars present similar spatial distribution, mainly distributed in the seed cortex and embryo with high abundance. The majority of amino acids are also concentrated in the rice cortex and embryo, while the others are abundant in the whole seed. Besides cinnamic acid distributed in the seed cortex and embryo, the naringenin chalcone, naringenin, and dihydrokaempferol were also found in the endosperm and had lower content. Furthermore, a colocalization phylogenetic tree according to the spatial distribution imaging of each metabolite was constructed. This study revealed the distribution diversity of metabolites in different segmentations of rice seed at the dough stage, providing clues for the nutritional differences between brown rice and white rice, and serving as a reference for people to target a healthy diet.PMID:37986446 | DOI:10.1016/j.foodres.2023.113578

Synergistic effect rescue animal model from NASH caused by diet-inflammation inducer

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113562. doi: 10.1016/j.foodres.2023.113562. Epub 2023 Oct 10.ABSTRACTExcessive intake of pro-inflammatory fatty acids is related to the development of insulin resistance, impaired oxidative stress enzymes, and lipid disorders, leading to inflammation and development of non-alcoholic steatohepatitis (NASH). Diet and physical exercise are considered to prevent and treat metabolic disorders caused by chronic inflammatory states (responsible for insulin resistance and diabetes type 2) in individuals with obesity and nonalcoholic fatty liver diseases (NAFLD). Our investigation tested the hypothesis that Hass avocado oil, a monounsaturated fatty acid and a source of phytosterol, may improve liver and metabolic parameters without adverse effects when combined with physical exercise. Rats ingested a high-fat diet for seven weeks and were then subjected to more six weeks with a standard diet, Hass avocado-oil ingestion, and swimming. The intervention showed significantly improvements by synergistic effect between Hass avocado-oil and swimming exercise (P < 0.05), including improving adiponectin, leptin, and fasting blood glucose levels, alleviating insulin resistance, reducing serum TNF-α, improving glutathione enzyme levels, and decreasing lipotoxicity in the liver and blood and serum triacylglycerides in blood (P < 0.05). Liver tissue markers of apoptosis and necrosis such as CK-18 filaments and dimethylamine (DMA) were significantly higher in the intervention group (P < 0.05). We were unable to fully confirm our hypothesis. Although the synergistic effects between Hass avocado-oil and the swimming regimen offer a promising chance of recovering liver health by improving 10 health biological markers, we must not ignore the cellular damage due to apoptosis and necrosis in liver cells and DMA. The data on metabolomic profile and avocado-oil-treated livers highlight the need for further investigation.PMID:37986439 | DOI:10.1016/j.foodres.2023.113562

Role of short germination and milling on physical properties, amino acid and metabolomic profiles of high amylose rice fractions

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113556. doi: 10.1016/j.foodres.2023.113556. Epub 2023 Oct 4.ABSTRACTShort germination is a process that can improve bioactive compounds in rice. This work aimed investigate the physical properties, phenolic compounds (PC), antioxidant activity and amino acids composition of husk + bran, brown and milled rice with high amylose content after short germination (16 h). α-amylase activity (Falling Number, FN) and enthalpy (ΔH) were unchanged (p < 0.05). RVA curve profiles were similar, even though after short germination and milling. Globally, metabolomics analysis identified 117 PC, in which 111 (bound), 104 (free) and 21 revealed in both extracts. p-Coumaric, trans-ferulic and ferulic acids were the most abundant PC revealed in all fractions. The portion husk + bran showed the highest level of total antioxidant activity (709.90 µmol TE) in both free and bound fractions. In terms of total amino acids, there was no statistical difference (p < 0.05) among non-germinated and germinated samples, contrary to free amino acids content. Glutamic acid (Glu) presented the highest values combining short germination and milling (1725-1900 mg/100 g) consequently, leads to higher value of GABA (12.21 mg/100 g). The combination of short germination and milling demonstrated a good strategy to improve the nutritional quality of rice, unless the thermal and pasting properties have been altered, contribute to potential health benefits on human nutrition.PMID:37986434 | DOI:10.1016/j.foodres.2023.113556

Effect of lactic acid bacteria co-fermentation on antioxidant activity and metabolomic profiles of a juice made from wolfberry and longan

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113547. doi: 10.1016/j.foodres.2023.113547. Epub 2023 Oct 4.ABSTRACTLactic acid bacteria (LAB) fermentation is frequently employed to improve the nutritional, functional, and sensory characteristics of foods. Our study explored the effects of co-fermentation with Lacticaseibacillus paracasei ZH8 and Lactococcus lactis subsp. lactis YM313 on the physicochemical properties, antioxidant activity, and metabolomic profiles of wolfberry-longan juice (WLJ). Fermentation was carried out at 35 °C for 15 h. The results suggest that WLJ is a favorable substrate for LAB growth, reaching a total viable count exceeding 8 log CFU/mL after fermentation. LAB fermentation increased acidity, reduced the sugar content, and significantly impacted the juice color. The total phenolic and flavonoid contents of the WLJ and the antioxidant capacities based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), ABTS radical scavenging abilities and FRAP were significantly improved by LAB fermentation. Nontargeted metabolomics analysis suggested that the contents of small molecule substances in WLJ were considerably affected by LAB fermentation. A total of 374 differential metabolites were identified in the juice before and after fermentation, with 193 significantly upregulated metabolites and 181 siginificantly downregulated metabolites. The regulation of metabolites is important for improving the flavor and functions of juices, such as L-eucylproline, Isovitexin, Netivudine, 3-Phenyllactic acid, vanillin, and ethyl maltol, ect. This study provides a theoretical foundation for developing plant-based foods fermented with LAB.PMID:37986427 | DOI:10.1016/j.foodres.2023.113547

Multi-omics analysis reveals the microbial interactions of S. cerevisiae and L. plantarum on Suanyu, Chinese traditional fermented fish

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113525. doi: 10.1016/j.foodres.2023.113525. Epub 2023 Sep 27.ABSTRACTS. cerevisiae and L. plantarum play important roles in Suanyu fermentation. This study investigated the interaction between S. cerevisiae and L. plantarum during fermentation and its impact on metabolic pathways. Co-culturing S. cerevisiae and L. plantarum increased pH to 5.72, reduced TVB-N to 9.47 mg/mL, and achieved high utilization rates of sugars (98.9%) and proteins (73.7%). During microbial interactions, S. cerevisiae and L. plantarum produced antibiotics, including phenyllactate and Gentamicin C1a, inhibiting the growth of each other. S. cerevisiae used S-adenosyl-l-methionine to counteract acid production of L. plantarum, establishing dominance in Suanyu fermentation. Microbial interactions influenced carbohydrate and energy metabolism pathways, such as nicotinate and nicotinamide metabolism and purine metabolism. S. cerevisiae significantly impacted gene expression in protein synthesis and cell growth pathways, including ribosome, SNARE interactions, basal transcription factors, and MAPK signaling. These findings offer insights into microbial interactions and metabolic processes during Suanyu fermentation.PMID:37986426 | DOI:10.1016/j.foodres.2023.113525

Integrated metabolomics and network pharmacology to reveal antioxidant mechanisms and potential pharmacological ingredients of citrus herbs

Tue, 21/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 1):113514. doi: 10.1016/j.foodres.2023.113514. Epub 2023 Sep 28.ABSTRACTThe benefits of citrus herbs are strongly associated with their secondary metabolites. In the study, we conducted widely-targeted metabolomics and ultra-high performance liquid chromatography (UPLC) to compare the variability of ingredients in four citrus herbs. In total, we discovered 1126 secondary metabolites, primarily comprising flavonoids, phenolic acids, lignans and coumarins, and alkaloids. Differential metabolites of citrus herbs were searched by multivariate statistical analysis. Notably, Citri Reticulatae Pericarpium contained higher levels of flavonoids, while Zhique and Huajuhong demonstrated a greater abundance of coumarins. Among the flavonoids determined by UPLC, Guangchenpi demonstrated significantly elevated levels of polymethoxyflavones (tangeretin and nobiletin) compared to other citrus herbs. Additionally, we determined their antioxidant capacity (Chenpi > Guangchenpi > Huajuhong > Zhique) using in vitro assays. Finally, we utilized network pharmacology to explore the antioxidant mechanisms and potential pharmacological ingredients, providing a basis for future preventive and therapeutic applications of these metabolites.PMID:37986422 | DOI:10.1016/j.foodres.2023.113514

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