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

Resequencing of global Lotus corniculatus accessions reveals population distribution and genetic loci, associated with cyanogenic glycosides accumulation and growth traits

Thu, 17/08/2023 - 12:00
BMC Biol. 2023 Aug 17;21(1):176. doi: 10.1186/s12915-023-01670-7.ABSTRACTBACKGROUND: Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered.RESULT: Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth.CONCLUSION: This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus.PMID:37592232 | DOI:10.1186/s12915-023-01670-7

The metabolic consequences of HIV/TB co-infection

Thu, 17/08/2023 - 12:00
BMC Infect Dis. 2023 Aug 18;23(1):536. doi: 10.1186/s12879-023-08505-4.ABSTRACTBACKGROUND: The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/tuberculosis (TB) co-infection remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise to host metabolic disruption and adaptations beyond that induced by only infection or disease.METHODS: In this study, the serum metabolic profiles of healthy controls, untreated HIV-negative TB-positive patients, untreated HIV/TB co-infected patients, and HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global metabolic profile for HIV/TB co-infection and the effect of ART has been published to date, this pilot study aimed to elucidate the general areas of metabolism affected during such conditions.RESULTS: HIV/TB co-infection induced significant changes to the host's lipid and protein metabolism, with additional microbial product translocation from the gut to the blood. The results suggest that HIV augments TB synergistically, at least in part, contributing to increased inflammation, oxidative stress, ART-induced mitochondrial damage, and its detrimental effects on gut health, which in turn, affects energy availability. ART reverses these trends to some extent in HIV/TB co-infected patients but not to that of healthy controls.CONCLUSION: This study generated several new hypotheses that could direct future metabolic studies, which could be combined with other research techniques or methodologies to further elucidate the underlying mechanisms of these changes.PMID:37592227 | DOI:10.1186/s12879-023-08505-4

Early ascending growth is associated with maternal lipoprotein profile during mid and late pregnancy and in cord blood

Thu, 17/08/2023 - 12:00
Int J Obes (Lond). 2023 Aug 17. doi: 10.1038/s41366-023-01361-x. Online ahead of print.ABSTRACTINTRODUCTION: Intrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth.METHODS: The RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings' first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm).RESULTS: From the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002).CONCLUSION: Ascending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, http://www.CLINICALTRIALS: com , NCT01698385.PMID:37592059 | DOI:10.1038/s41366-023-01361-x

Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells

Thu, 17/08/2023 - 12:00
Nat Commun. 2023 Aug 17;14(1):4634. doi: 10.1038/s41467-023-40222-z.ABSTRACTDeregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic reprogramming, stable isotope-assisted metabolomics reveals that deregulated pyruvate anaplerosis is not affected by imatinib. Encouragingly, genetic ablation of pyruvate anaplerosis sensitises CML cells to imatinib. Finally, we demonstrate that MSDC-0160, a clinical orally-available MPC1/2 inhibitor, inhibits pyruvate anaplerosis and targets imatinib-resistant CML LSCs in robust pre-clinical CML models. Collectively these results highlight pyruvate anaplerosis as a persistent and therapeutically targetable vulnerability in imatinib-treated CML patient-derived samples.PMID:37591854 | DOI:10.1038/s41467-023-40222-z

Key metabolomic alterations are associated with ulcerative colitis disease state and activity: a validation analysis

Thu, 17/08/2023 - 12:00
Gut. 2023 Aug 17:gutjnl-2023-330196. doi: 10.1136/gutjnl-2023-330196. Online ahead of print.NO ABSTRACTPMID:37591699 | DOI:10.1136/gutjnl-2023-330196

CD44 acts as a coreceptor for cell-specific enhancement of signaling and regulatory T cell induction by TGM1, a parasite TGF-β mimic

Thu, 17/08/2023 - 12:00
Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2302370120. doi: 10.1073/pnas.2302370120. Epub 2023 Aug 17.ABSTRACTLong-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, Heligmosomoides polygyrus, down-modulates the host immune system through release of an immunosuppressive TGF-β mimic, TGM1, which is a divergent member of the CCP (Sushi) protein family. TGM1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGF-β receptors, acting on T cells to induce Foxp3+ regulatory T cells; however, the roles of domains 4 and 5 (D4/5) remain unknown. We noted that truncated TGM1, lacking D4/5, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not alter potency, suggesting that a physical linkage is required and that these domains do not deliver an independent signal. Coprecipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a coreceptor for TGM1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, to a greater degree than D1/2/3 alone, although some cell lines did not respond to TGM1. Ectopic expression of CD44 in nonresponding cells conferred responsiveness, while genetic depletion of CD44 abolished enhancement by D4/5 and ablated the ability of full-length TGM1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM1, to levels similar to those induced by D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type-specific potency of TGF-β signaling in mammalian cells.PMID:37590410 | DOI:10.1073/pnas.2302370120

Analysis of polar primary metabolites in biological samples using targeted metabolomics and LC-MS

Thu, 17/08/2023 - 12:00
STAR Protoc. 2023 Aug 16;4(3):102400. doi: 10.1016/j.xpro.2023.102400. Online ahead of print.ABSTRACTPrimary metabolites are molecules of essential biochemical reactions that define the biological phenotype. All primary metabolites cannot be measured in a single analysis. In this protocol, we outline the multiplexed and quantitative measurement of 106 metabolites that cover the central part of primary metabolism. The protocol includes several sample preparation techniques and one liquid chromatography-mass spectrometry method. Then, we describe the steps of the bioinformatic data analysis to better understand the metabolic perturbations that may occur in a biological system. For complete details on the use and execution of this protocol, please refer to: Costanza et al.,1 Blomme et al.,2 Blomme et al.,3 Guillon et al.,4 Stuani et al.5.PMID:37590149 | DOI:10.1016/j.xpro.2023.102400

Anti-infective potential of the endophytic fungus <em>Aspergillus</em> sp. associated with <em>Aptenia cordifolia</em> root supported by metabolomics analysis and docking studies

Thu, 17/08/2023 - 12:00
Nat Prod Res. 2023 Aug 17:1-6. doi: 10.1080/14786419.2023.2245114. Online ahead of print.ABSTRACTEndophytic fungi are known to be a rich source for anti-infective drugs. In this study, Aptenia cordifolia associated endophytic fungi were explored for the first time. Seven isolates were identified morphologically followed by screening of these fungi by plug diffusion assay which revealed their potential activity against Staphylococcus aureus (ATCC 9144), Bacillus cereus (ATCC 14579), Serratia marcescens (ATCC 14756), Fusarium oxysporum (ATCC 48112), and Aspergillus flavus (ATCC 22546). Additionally, the crude ethyl acetate extract of the most potent three isolates in plug diffusion assay showed that Aspergillus sp. ACEFR2 was the most potent as anti-infective in disc diffusion assay; Accordingly, Aspergillus sp. ACEFR2 was investigated using phylogenetic analysis and LC-HR-ESI-MS. The phylogenetic analysis placed the strain into the Aspergillus section Niger close related to few species including A. niger. Whereas the metabolomic profiling revealed the presence of diverse pool of metabolites. Furthermore, in silico molecular docking study was carried out to predict which compounds most likely responsible for the anti-infective activity.PMID:37590004 | DOI:10.1080/14786419.2023.2245114

Metabolomic and physiological changes of acid-tolerant Graesiella sp. MA1 during long-term acid stress

Thu, 17/08/2023 - 12:00
Environ Sci Pollut Res Int. 2023 Aug 17. doi: 10.1007/s11356-023-29295-x. Online ahead of print.ABSTRACTAlgae plays a significant role for the primary production in the oligotrophic ecosystems such as the acid mine pit lakes. Graesiella sp. MA1 was a new acid-tolerant photosynthetic protist isolated from an acid mine pit lake. To understand the acid responses of Graesiella sp. MA1, its physiological changes and metabolomics were studied during long-term acid stress. Photosynthetic pigments, soluble proteins, and antioxidant systems of Graesiella sp. MA1 cells displayed two phases, the adaptation phase and the growth phase. During the adaptation phase, both photosynthetic pigments and soluble proteins were inhibited, while antioxidant activity of SOD, APX, and GSH were promoted to response to the organism's damage. Metabolomics results revealed lipids and organic acids were abundant components in Graesiella sp. MA1 cells. In response to acid stress, the levels of acid-dependent resistant amino acids, including glutamate, aspartate, arginine, proline, lysine, and histidine, accumulated continuously to maintain orderly intracellular metabolic processes. In addition, fatty acids were mainly unsaturated, which could improve the fluidity of the cell membranes under acid stress. Metabolomic and physiological changes showed that Graesiella sp. MA1 had tolerance during long-term acid stress and the potential to be used as a bioremediation strain for the acidic wastewater.PMID:37589846 | DOI:10.1007/s11356-023-29295-x

Characterizing the metabolic response of the zebrafish kidney to overfeeding

Thu, 17/08/2023 - 12:00
Am J Physiol Renal Physiol. 2023 Aug 17. doi: 10.1152/ajprenal.00113.2023. Online ahead of print.ABSTRACTObesity is a global epidemic and risk factor for the development of chronic kidney disease. Obesity induces systemic changes in metabolism, but how it affects kidney metabolism specifically is not known. Zebrafish have previously been shown to develop obesity related kidney pathology and dysfunction when fed hypercaloric diets. To understand the direct effects of obesity on kidney metabolic function, we treated zebrafish for 8 weeks with a control and an overfeeding diet. At the end of treatment, we assessed changes in kidney and fish weights and used electron microscopy to evaluate cell ultrastructure. We then performed an untargeted metabolomic analysis on the kidney tissue of fish using ultra-high performance liquid chromatography coupled high-resolution mass spectrometry, and used mummichog and gene set enrichment analysis to uncover differentially affected metabolic pathways. Kidney metabolomes differed significantly and consistently between the control and overfed diets. Among 9593 features, we identified 235 which were significantly different (p<0.05) between groups (125 upregulated in overfed diet, 110 downregulated). Pathway analysis demonstrated perturbations in glycolysis and fatty acid synthesis pathways, and analysis of specific metabolites points to perturbations in tryptophan metabolism. Our key findings show that diet induced obesity leads to metabolic changes in the kidney tissue itself and implicate specific metabolic pathways, including glycolysis and tryptophan metabolism in the pathogenesis of obesity related kidney disease, demonstrating the power of untargeted metabolomics to identify pathways of interest by directly interrogating kidney tissue.PMID:37589050 | DOI:10.1152/ajprenal.00113.2023

Propionibacteria as promising tools for the production of pro-bioactive scotta: a proof-of-concept study

Thu, 17/08/2023 - 12:00
Front Microbiol. 2023 Jul 31;14:1223741. doi: 10.3389/fmicb.2023.1223741. eCollection 2023.ABSTRACTDairy propionibacteria are Gram positive Actinomycetota, routinely utilized as starters in Swiss type cheese making and highly appreciated for their probiotic properties and health promoting effects. In this work, within the frame of a circular economy approach, 47 Propionibacterium and Acidipropionibacterium spp. were isolated from goat cheese and milk, and ewe rumen liquor, and characterized in view of their possible utilization for the production of novel pro-bioactive food and feed on scotta, a lactose rich substrate and one of the main by-products of the dairy industry. The evaluation of the Minimum Inhibitory Concentration (MIC) of 13 among the most common antibiotics in clinical practice revealed a general susceptibility to ampicillin, gentamycin, streptomycin, vancomycin, chloramphenicol, and clindamycin while confirming a lower susceptibility to aminoglycosides and ciprofloxacin. Twenty-five isolates, that proved capable of lactose utilization as the sole carbon source, were then characterized for functional and biotechnological properties. Four of them, ascribed to Propionibacterium freudenreichii species, and harboring resistance to bile salts (growth at 0.7-1.56 mM of unconjugated bile salts), acid stress (>80% survival after 1 h at pH 2), osmostress (growth at up to 6.5% NaCl) and lyophilization (survival rate > 80%), were selected and inoculated in scotta. On this substrate the four isolates reached cell densities ranging from 8.11 ± 0.14 to 9.45 ± 0.06 Log CFU mL-1 and proved capable of producing different vitamin B9 vitamers after 72 h incubation at 30°C. In addition, the semi-quantitative analysis following the metabolomics profiling revealed a total production of cobalamin derivatives (vitamin B12) in the range 0.49-1.31 mg L-1, thus suggesting a full activity of the corresponding biosynthetic pathways, likely involving a complex interplay between folate cycle and methylation cycle required in vitamin B12 biosynthesis. These isolates appear interesting candidates for further ad-hoc investigation regarding the production of pro-bioactive scotta.PMID:37588883 | PMC:PMC10425813 | DOI:10.3389/fmicb.2023.1223741

Widely targeted metabolomics analysis of different Wuyi Shuixian teas and association with taste attributes

Thu, 17/08/2023 - 12:00
Heliyon. 2023 Aug 5;9(8):e18891. doi: 10.1016/j.heliyon.2023.e18891. eCollection 2023 Aug.ABSTRACTThere are two major types of Wuyi Shuixian teas with distinct flavor properties in the market: regular Shuixian, and Laocong Shuixian that is produced from old tea plants with higher sale price. However, the chemical composition difference between these two types of Shuixian teas is still unclear. In this study, the widely targeted metabonomics and sensory evaluation were carried out to investigate the metabolite profiles and the flavor properties of Laocong and regular Shuixian tea samples. The results of organoleptic evaluation showed the Laocong Shuixian teas achieved dramatically higher total scores of sensory quality than that of regular Shuixian, and the sour palate of Laocong Shuixian tea was much lower than that of regular Shuxian. A total of 692 metabolites were identified by using metabolic determination, 43 of which were different metabolites in Laocong Shuixian teas discriminated from regular Shuixian. The contents of caffeic acid, kaemperfin, genistin, quercetin 3-glycosides and p-coumaric acid-O-glycoside were abundantly present in regular Shuixian tea. The analysis on different metabolites and taste attributes showed that phenolic acidic compounds were the major contributors to the sour taste of regular Shuixian. This study interpreted the chemicals underlying the different taste properties of Laocong and regular Shuixian teas.PMID:37588613 | PMC:PMC10425894 | DOI:10.1016/j.heliyon.2023.e18891

Plasma metabolomic signatures of breast cancer

Thu, 17/08/2023 - 12:00
Front Med (Lausanne). 2023 Jul 31;10:1148542. doi: 10.3389/fmed.2023.1148542. eCollection 2023.ABSTRACTBACKGROUND: Breast cancer is a common malignant tumor. A large number of medical evidence shows that breast cancer screening can improve the early diagnosis rate and reduce the mortality rate of breast cancer. In the present study, a wide range of targeted metabolomics profiling was conducted to investigate the plasma signatures of breast cancer.METHODS: A total of 86 patients with benign breast abnormalities (L group) and 143 patients with breast cancer (E group) were recruited. We collected their plasma samples and clinical information. Metabolomic analysis, based on the coverage of a wide range of targeted metabolomics was conducted with ultraperformance liquid chromatography- triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS).RESULTS: We identified 716 metabolites through widely-targeted metabolomics. Serotonergic synapse was the main different metabolic pathway. The fold change of 14 metabolites was considered significantly different (fold change <0.67 or fold change >2; p < 0.05). By combining all the 14 metabolites, we achieved differentiation of L group vs. E group (AUC = 0.792, 95%Cl: 0.662-0.809).CONCLUSION: This study provided new insights into plasma biomarkers for differential diagnosis of benign abnormalities and breast cancer.PMID:37588002 | PMC:PMC10425771 | DOI:10.3389/fmed.2023.1148542

Mass spectrometry as a lens into molecular human nutrition and health

Thu, 17/08/2023 - 12:00
Eur J Mass Spectrom (Chichester). 2023 Aug 16:14690667231193555. doi: 10.1177/14690667231193555. Online ahead of print.ABSTRACTMass spectrometry (MS) has developed over the last decades into the most informative and versatile analytical technology in molecular and structural biology (). The platform enables discovery, identification, and characterisation of non-volatile biomolecules, such as proteins, peptides, DNA, RNA, nutrients, metabolites, and lipids at both speed and scale and can elucidate their interactions and effects. The versatility, robustness, and throughput have rendered MS a major research and development platform in molecular human health and biomedical science. More recently, MS has also been established as the central tool for 'Molecular Nutrition', enabling comprehensive and rapid identification and characterisation of macro- and micronutrients, bioactives, and other food compounds. 'Molecular Nutrition' thereby helps understand bioaccessibility, bioavailability, and bioefficacy of macro- and micronutrients and related health effects. Hence, MS provides a lens through which the fate of nutrients can be monitored along digestion via absorption to metabolism. This in turn provides the bioanalytical foundation for 'Personalised Nutrition' or 'Precision Nutrition' in which design and development of diets and nutritional products is tailored towards consumer and patient groups sharing similar genetic and environmental predisposition, health/disease conditions and lifestyles, and/or objectives of performance and wellbeing. The next level of integrated nutrition science is now being built as 'Systems Nutrition' where public and personal health data are correlated with life condition and lifestyle factors, to establish directional relationships between nutrition, lifestyle, environment, and health, eventually translating into science-based public and personal heath recommendations and actions. This account provides a condensed summary of the contributions of MS to a precise, quantitative, and comprehensive nutrition and health science and sketches an outlook on its future role in this fascinating and relevant field.PMID:37587732 | DOI:10.1177/14690667231193555

Metabolic remission precedes possible weight regain after gastric bypass surgery

Thu, 17/08/2023 - 12:00
Obesity (Silver Spring). 2023 Aug 16. doi: 10.1002/oby.23864. Online ahead of print.ABSTRACTOBJECTIVE: Some patients regain weight to a variable extent from 1 year after Roux-en-Y gastric bypass surgery (RYGB), though rarely reaching preoperative values. The aim of the present study was to investigate whether, when, and to what extent metabolic remission occurs.METHODS: Fasting metabolite and lipid profiles were determined in blood plasma collected from a nonrandomized intervention study involving 148 patients before RYGB and at 2, 12, and 60 months post RYGB. Both short-term and long-term alterations in metabolism were assessed. Anthropometric and clinical variables were assessed at all study visits.RESULTS: This study found that the vast majority of changes in metabolite levels occurred during the first 2 months post RYGB. Notably, thereafter the metabolome started to return toward the presurgical state. Consequently, a close-to-presurgical metabolome was observed at the time when patients reached their lowest weight and glucose level. Lipids with longer acyl chains and a higher degree of unsaturation were altered more dramatically compared with shorter and more saturated lipids, suggesting a systematic and reversible lipid remodeling.CONCLUSIONS: Remission of the metabolic state was observed prior to notable weight regain. Further and more long-term studies are required to assess whether the extent of metabolic remission predicts future weight regain and glycemic deterioration.PMID:37587639 | DOI:10.1002/oby.23864

WEIGHT REGAIN AND THE METABOLIC PROFILE OF WOMEN IN THE POSTOPERATIVE PERIOD OF BARIATRIC SURGERY: A MULTIVARIATE ANALYSIS

Wed, 16/08/2023 - 12:00
Arq Bras Cir Dig. 2023 Aug 14;36:e1755. doi: 10.1590/0102-672020230037e1755. eCollection 2023.ABSTRACTBACKGROUND: Weight regain in the postoperative period after bariatric surgery is directly related to the relapse of preoperative comorbidities and a negative impact on the patients' biochemical profile.AIMS: To assess the metabolic impact of weight regain on preoperative comorbidities and on patients' biochemical profiles, in order to show the impact of the complications on the metabolic outcomes of bariatric surgery.METHODS: A retrospective study was carried out with 75 women in the late postoperative period of bariatric surgery who presented pathological weight regain (≥20% of the maximum weight loss). Data of interest consisted of glycemic, lipid, and inflammatory profile measurements at three different moments of evaluation: preoperative period, at the weight nadir (minimum weight), and after weight regain. A multivariate analysis was performed.RESULTS: The mean age was 46.39±12.09 years. Preoperative body mass index was 40.10±4.11 kg/m2. There was an overall increase of 3.36 points in the mean body mass index between the nadir and after regain: from 26.30±3.9 kg/m2 to 29.66±4.66 kg/m2. The mean time to reach the nadir was 18±7.6 months, with an average percentage of excess weight loss of 91.08±11.8%. The median time for pathological weight regain was 48 months, and the mean regain amongst the sample was 8.85±5.65 kg. There was a significant correlation between pathological weight regain and levels of insulin (r=0.351; p<0.011), C-peptide (r=0.303; p<0.011), C-reactive protein (r=0.402; p<0.001), and vitamin D (r=-0.435; p<0.001), the last two being the most influenced by the percentage of weight regained.CONCLUSIONS: The pathological weight regain in the postoperative period of bariatric surgery results in losses in the patients' metabolic and inflammatory profiles. However, the biochemical benefits are sustained up to the preoperative levels of the parameters analyzed.PMID:37585909 | DOI:10.1590/0102-672020230037e1755

Integrated lipidomic and transcriptomic analysis reveals diacylglycerol accumulation in olive of Longnan (China)

Wed, 16/08/2023 - 12:00
PeerJ. 2023 Aug 11;11:e15724. doi: 10.7717/peerj.15724. eCollection 2023.ABSTRACTBACKGROUND: Olive (Olea europaea L.) oil accumulate more diacylglycerols (DAG) than mostly vegetable oils. Unsaturated fatty acids-enriched DAG consumption enhanced wellness in subjects. However, the mechanism of DAG accumulation is not yet fully understood.METHODS: In this study, gene network of DAG accumulation and fatty acid composition in the two olive mesocarps ("Chenggu 32" (CG) and "Koroneiki" (QJ)) were investigated by integrating lipidome and transcriptome techniques.RESULTS: A total of 1,408 lipid molecules were identified by lipidomic analysis in olive mesocarp, of which DAG (DAG36:3, DAG36:4 and DAG36:5) showed higher content, and triacylglycerols (TAG54:3, TAG54:4) exhibited opposite trend in CG. Specifically, DAG was rich in polyunsaturated fatty acids (especially C18:2) at the sn-2 position, which was inconsistent with TAG at the same positions (Primarily C18:1). Transcriptomic analysis revealed that phospholipase C (NPC, EC 3.1.4.3) were up-regulated relative to QJ, whereas diacylglycerol kinase (ATP) (DGK, EC 2.7.1.107), diacylglycerol acyltransferase (DGAT, EC 2.3.1.20), and phospholipid: diacylglycerol acyltransferase (PDAT, EC 2.3.1.158) were down-regulated.CONCLUSION: We speculated that the non-acyl coenzyme A pathway played a significant role in DAG biosynthesis. Additionally, fatty acyl-ACP thioesterase B (FATB, EC 3.1.2.14), stearoyl [acyl-carrier-protein] 9-desaturase (SAD, EC 1.14.19.2) and omega-6 fatty acid desaturase (FAD2, EC 1.14.19.6) were highly expressed in CG and may be involved in regulating fatty acid composition. Meanwhile, phospholipase A1 (LCAT, EC 3.1.1.32) involved in the acyl editing reaction facilitated PUFA linkage at the sn-2 position of DAG. Our findings provide novel insights to increase the DAG content, improve the fatty acid composition of olive oil, and identify candidate genes for the production of DAG-rich oils.PMID:37583911 | PMC:PMC10424668 | DOI:10.7717/peerj.15724

Toxicity effects of pesticides based on zebrafish (Danio rerio) models: Advances and perspectives

Wed, 16/08/2023 - 12:00
Chemosphere. 2023 Aug 14:139825. doi: 10.1016/j.chemosphere.2023.139825. Online ahead of print.ABSTRACTPesticides inevitably enter aquatic environments, posing potential risks to organisms. The common aquatic model organism, zebrafish (Danio rerio), are widely used to evaluate the toxicity of pesticides. In this review, we searched the Web of Science database for articles published between 2012 and 2022, using the keywords "pesticide", "zebrafish", and "toxicity", retrieving 618 publications. Furthermore, we described the main pathways by which pesticides enter aquatic environments and the fate of their residues in these environments. We systematically reviewed the toxicity effects of pesticides on zebrafish, including developmental toxicity, endocrine-disrupting effects, reproductive toxicity, neurotoxicity, immunotoxicity, and genotoxicity. Importantly, we summarized the latest research progress on the toxicity mechanism of pesticides to zebrafish based on omics technologies, including transcriptomics, metabolomics, and microbiomics. Finally, we discussed future research prospects, focusing on the combined exposure of multiple pollutants including pesticides, the risk of multigenerational exposure to pesticides, and the chronic toxicity of aquatic nanopesticides. This review provides essential data support for ecological risk assessments of pesticides in aquatic environments, and has implications for water management in the context of pesticide pollution.PMID:37586498 | DOI:10.1016/j.chemosphere.2023.139825

Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects

Wed, 16/08/2023 - 12:00
Cell Rep Med. 2023 Aug 9:101157. doi: 10.1016/j.xcrm.2023.101157. Online ahead of print.ABSTRACTTo evaluate whether nicotinamide adenine dinucleotide-positive (NAD+) boosting modulates adaptive immunity, primary CD4+ T cells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies that NAD+ boosting increases arginine and fumarate biosynthesis, and genetic knockdown of argininosuccinate lyase ameliorates NR effects on IL-17 production. Hence NR via amino acid metabolites orchestrates Nrf2 activation, augments CD4+ T cell antioxidant defenses, and attenuates Th17 responsiveness. Oral NR supplementation in healthy volunteers similarly increases serum arginine, sqstm1, and antioxidant enzyme gene expression and blunts Th17 immune responsiveness, supporting evaluation of NAD+ boosting in CD4+ T cell-linked inflammation.PMID:37586364 | DOI:10.1016/j.xcrm.2023.101157

Integrated transcriptomic and metabolomic analysis reveals the response of pearl oyster (Pinctada fucata martensii) to long-term hypoxia

Wed, 16/08/2023 - 12:00
Mar Environ Res. 2023 Aug 10;191:106133. doi: 10.1016/j.marenvres.2023.106133. Online ahead of print.ABSTRACTThe frequency at which organisms are exposed to hypoxic conditions in aquatic environments is increasing due to coastal eutrophication and global warming. To reveal the effects of long-term hypoxic stress on metabolic changes of pearl oyster, commonly known as Pinctada (Pinctada fucata martensii), the present study performed the integrated analysis of transcriptomics and metabolomics to investigate the global changes of genes and metabolites following 25 days hypoxia challenge. Transcriptome analysis detected 1108 differentially expressed genes (DEGs) between the control group and the hypoxia group. The gene ontology (GO) analysis of DEGs revealed that they are significantly enriched in functions such as "microtubule-based process", "histone (H3-K4, H3-K27, and H4-K20) trimethylation", "histone H4 acetylation", "kinesin complex", and "ATPase activity", and KEGG pathway functions, such as "DNA replication", "Apoptosis", and "MAPK signaling pathways". Metabolome analysis identified 68 significantly different metabolites from all identified metabolites, and associated with 25 metabolic pathways between the control and hypoxia groups. These pathways included aminoacyl-tRNA biosynthesis, arginine and proline metabolism, and phenylalanine metabolism. Our integrated analysis suggested that pearl oysters were subject to oxidative stress, apoptosis, immune inhibition, and neuronal excitability reduction under long-term hypoxic conditions. We also found a remarkable depression in a variety of biological functions under long-term hypoxia, including metabolic rates, biomineralization activities, and the repression of reorganization of the cytoskeleton and cell metabolism. These findings provide a basis for elucidating the mechanisms used by marine bivalves to cope with long-term hypoxic stress.PMID:37586225 | DOI:10.1016/j.marenvres.2023.106133

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