PubMed

Plant Sci. 2023 Nov 7:111917. doi: 10.1016/j.plantsci.2023.111917. Online ahead of print.ABSTRACTAcer truncatum is a horticultural tree species with individuals that display either yellow or red leaves in autumn, giving it high ornamental and economic value. 'Lihong' of A. truncatum is an excellent cultivar due to its characteristic of having autumn leaves that turn a bright and beautiful shade of red, while its closely related cultivar 'Bunge' does not. However, the molecular mechanism underlying the color change in the cultivar 'Lihong' is still unclear. Here, we assembled a high-quality genome sequence of Acer truncatum 'Lihong' (genome size = 688Mb, scaffold N50 = 9.14Mb) with 28,438 protein-coding genes predicted. Through comparative genomic analysis, we found that 'Lihong' had experienced more tandem duplication events although it's a high degree of collinearity with 'Bunge'. Especially, the expansion of key enzymes in the anthocyanin synthesis pathway was significantly uneven between the two varieties, with 'Lihong' genome containing a significantly higher number of tandem/dispersed duplication key genes. Further transcriptomic, metabolomic, and molecular functional analyses demonstrated that several UFGT genes, mainly resulting from tandem/dispersed duplication, followed by the promoter sequence variation, may contribute greatly to the leaf color phenotype, which provides new insights into the mechanism of divergent anthocyanin accumulation process in the 'Lihong' and 'Bunge' with yellow leaves in autumn. Further, constitutive expression of two UFGT genes, which showed higher expression in 'Lihong', elevated the anthocyanin content. We proposed that the small-scale duplication events could contribute to phenotype innovation.PMID:37944703 | DOI:10.1016/j.plantsci.2023.111917

Ecotoxicol Environ Saf. 2023 Nov 7;267:115637. doi: 10.1016/j.ecoenv.2023.115637. Online ahead of print.ABSTRACTA variety of microplastics (MPs) have become ubiquitous environmental pollutants, leading to inevitable human contact and health impacts. Most previous research has explored the toxic effects of a single type of MPs exposure. However, the effects of co-exposure to both common types of MPs, polyvinyl chloride (PVC) and polystyrene (PS) MPs on mammals have not been explored. Here, adult mice were exposed to PS-PVC (1.0 µm PS and 2.0 µm PVC both at the concentration of 0.5 mg/day) for 60 days. The results showed that PS-PVC co-exposure-induced hepatotoxicity was evidenced by liver histopathological changes, the release of inflammatory cytokines, and the activation of oxidative stress. Moreover, the intestinal mucosal barrier was damaged after PS-PVC treatment. The results of 16S rRNA gene sequencing reported there was a marked shift in the gut microbial structure accompanied by decreased relative abundances of probiotics, such as Clostridium, Lachnospiraceae_UCG-006, Desulfovibrio, Clostridiales_unclassified and Ruminococcaceae_unclassified and increased the conditional pathogen abundances, such as Erysipelatoclostridium. Furthermore, the triglyceride (TG) and total cholesterol (TCH) expression levels in the serum and liver were increased after PS-PVC co-exposure. Serum metabolomics analysis showed that there were 717 differential expression metabolites found in the positive- and negative-ion modes, including 476 up-regulated and 241 down-regulated, mainly enriched in butyrate metabolism, thiamine metabolism, and phenylacetate metabolism. In addition, remarked changes in the gut microbiota and serum metabolic profiles were closely related to hepatic and intestinal injuries after PS-PVC co-exposure. These results have provided new insights into the toxic effects of PS and PVC MPs co-exposure through the gut-liver axis and the health risks of PS and PVC MPs should be paid more attention to humans.PMID:37944461 | DOI:10.1016/j.ecoenv.2023.115637

Biomed Pharmacother. 2023 Nov 7;169:115775. doi: 10.1016/j.biopha.2023.115775. Online ahead of print.ABSTRACTPsychedelics are classical hallucinogen drugs that induce a marked altered state of consciousness. In recent years, there has been renewed attention to the possible use of classical psychedelics for the treatment of certain mental health disorders. However, further investigation to better understand their biological effects in humans, their mechanism of action, and their metabolism in humans is needed when considering the development of future novel therapeutic approaches. Both metabolic and metabolomics studies may help for these purposes. On one hand, metabolic studies aim to determine the main metabolites of the drug. On the other hand, the application of metabolomics in human psychedelics studies can help to further understand the biological processes underlying the psychedelic state and the mechanisms of action underlying their therapeutic potential. This review presents the state of the art of metabolic and metabolomic studies after lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT) and β-carboline alkaloids (ayahuasca brew), 5-methoxy-DMT and psilocybin administrations in humans. We first describe the characteristics of the published research. Afterward, we reviewed the main results obtained by both metabolic and metabolomics (if available) studies in classical psychedelics and we found out that metabolic and metabolomics studies in psychedelics progress at two different speeds. Thus, whereas the main metabolites for classical psychedelics have been robustly established, the main metabolic alterations induced by psychedelics need to be explored. The integration of metabolomics and pharmacokinetics for investigating the molecular interaction between psychedelics and multiple targets may open new avenues in understanding the therapeutic role of psychedelics.PMID:37944438 | DOI:10.1016/j.biopha.2023.115775

J Biol Chem. 2023 Nov 7;299(12):105422. doi: 10.1016/j.jbc.2023.105422. Online ahead of print.NO ABSTRACTPMID:37944340 | DOI:10.1016/j.jbc.2023.105422

Aquat Toxicol. 2023 Nov 3;265:106745. doi: 10.1016/j.aquatox.2023.106745. Online ahead of print.ABSTRACTDespite growing interest in conventional microplastics (CMPs) and their toxicological effects on aquatic species, little is known about biodegradable microplastics (BMPs) and their corresponding implications for aquatic life. Here, tilapia (Oreochromis mossambicus) were semi-statically exposed for 14 days to the bio-based plastic polylactic acid (PLA, 100 μg/L, 2.52 ± 0.46 μm) and the petroleum-based plastic polyvinyl chloride (PVC, 100 μg/L, 1.58 ± 0.36 μm). The results showed that ingesting the above two types of microplastics (MPs) led to oxidative stress in the fish gut, and damage to gut tissues and organelles, and PLA resulted in more obvious gut tissue edema than PVC. Furthermore, PLA caused increased levels of gut microbiota dysbiosis and a decrease in the abundance of the genus Cetobacterium, which is linked to vitamin B-12 synthesis, whereas an opposite relationship was observed on PVC. Metabolomic analysis indicated that PVC caused a significant down-regulation of orotic acid, co-metabolite of folic acid with vitamin B-12, while PLA did not affect orotic acid, which may lead to the accumulation of folic acid in fish. The joint analysis found that MPs disturbed gut metabolism homeostasis, implying that abnormal gut microbiota metabolites may be a key mechanism for MPs to induce tissue damage and oxidative stress in the gut. Overall, this study systematically illustrates the differential toxic effects of BMPs and CMPs on tilapia through gut microbiota and metabolite interactions, which will contribute to assessing the risks of BMPs to organismal health.PMID:37944327 | DOI:10.1016/j.aquatox.2023.106745

J Plant Physiol. 2023 Oct 28;291:154124. doi: 10.1016/j.jplph.2023.154124. Online ahead of print.ABSTRACTHalophytes are potential future crops with a valuable nutritional profile. Produced in indoor farming, they are considered to contribute to sustainable and resilient food systems. Indoor farms operate using artificial light. In this context narrowband and low dose UVB radiation can be used to increase plant secondary metabolites, such as carotenoids, and provide an improved nutritional profile for a human diet. UVB radiation can cause eustress or distress in the plant depending on the lighting situation. The aim of this study was to identify the doses of UVB that lead to either eustress or distress and to analyze these responses in Salicornia europaea. Therefore, S. europaea plants were exposed to different UVB radiation levels, low, medium and high, and analyzed for reactive oxygen species (ROS), plant hormones, amino acids, and photosynthetic pigments. High UVB treatment was found to affect phenotype and growth, and the metabolite profile was affected in a UVB dose-dependent manner. Specifically, medium UVB radiation resulted in an increase in carotenoids, whereas high UVB resulted in a decrease. We also observed an altered oxidative stress status and increased SA and decreased ABA contents in response to UVB treatment. This was supported by the results of menadione treatment that induces oxidative stress in plants, which also indicated an altered oxidative stress status in combination with altered carotenoid content. Thus, we show that a moderate dose of UVB can increase the carotenoid content of S. europaea. Furthermore, the UVB stress-dependent response led to a better understanding of carotenoid accumulation upon UVB exposure, which can be used to improve lighting systems and in turn the nutritional profile of future crops in indoor farming.PMID:37944241 | DOI:10.1016/j.jplph.2023.154124

Int Immunopharmacol. 2023 Nov 7;125(Pt A):111170. doi: 10.1016/j.intimp.2023.111170. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Neuropathic pain (NeP) induced dysbiosis of intestinal microbiota in chronic constriction injury (CCI) rats. Emodin has analgesic effect but the detailed mechanism is not clear at the present time. This study aims to explore the underling mechanism of action of emodin against NeP with in CCI model.METHODS: Male SD rats (180-220 g) were randomly divided into three groups: sham group, CCI group, and emodin group. Behavioral tests were performed to evaluate the therapeutic effects of emodin on CCI model. Feces and spinal cords of all rats were collected 15 days after surgery. 16S rDNA sequencing, untargeted metabolomics, qPCR and ELISA were performed.RESULTS: Mechanical withdrawal thresholds (MWT), thermal withdrawal latency (TWL) and Sciatic functional index (SFI) in emodin group were significantly higher than CCI group (P < 0.05). Emodin not only inhibited the expression of pro-inflammatory cytokines in the spinal cords and colonic tissue, but also increased the expression of tight junction protein in colonic tissue. 16S rDNA sequencing showed that emodin treatment changed the community structure of intestinal microbiota in CCI rats. Untargeted metabolomics analysis showed that 33 differential metabolites were screened out between CCI group and emodin group. After verification, we found that emodin increased the level of S-adenosylmethionine (SAM) and Histamine in the spinal cord of CCI rats.CONCLUSION: Emodin was effective in relieving neuropathic pain, which is linked to inhibition inflammatory response, increasing the proportion of beneficial bacteria and beneficial metabolites.PMID:37944218 | DOI:10.1016/j.intimp.2023.111170

J Clin Oncol. 2023 Nov 9:JCO2202754. doi: 10.1200/JCO.22.02754. Online ahead of print.ABSTRACTPURPOSE: To provide an overview on how the application of metabolomics (high-throughput characterization of metabolites from cells, organs, tissues, or biofluids) to population-based studies may inform our understanding of breast cancer etiology.METHODS: We evaluated studies that applied metabolomic analyses to prediagnostic blood samples from prospective epidemiologic studies to identify circulating metabolites associated with breast cancer risk, overall and by breast cancer subtype and menopausal status. We provide some important considerations for the application and interpretation of metabolomics approaches in this context.RESULTS: Overall, specific lipids and amino acids were indicated as the most common metabolite classes associated with breast cancer development. However, comparison of results across studies is challenging because of heterogeneity in laboratory techniques, analytical methods, sample size, and applied statistical methods.CONCLUSION: Metabolomics is being increasingly applied to population-based studies for the identification of new etiologic hypotheses and/or mechanisms related to breast cancer development. Despite its success in applications to epidemiology, studies of larger sample size with detailed information on menopausal status, breast cancer subtypes, and repeated biologic samples collected over time are needed to improve comparison of results between studies and enhance validation of results, allowing potential clinical translation of findings.PMID:37944067 | DOI:10.1200/JCO.22.02754

PLoS Pathog. 2023 Nov 9;19(11):e1011787. doi: 10.1371/journal.ppat.1011787. Online ahead of print.ABSTRACTPlasma of COVID-19 patients contains a strong metabolomic/lipoproteomic signature, revealed by the NMR analysis of a cohort of >500 patients sampled during various waves of COVID-19 infection, corresponding to the spread of different variants, and having different vaccination status. This composite signature highlights common traits of the SARS-CoV-2 infection. The most dysregulated molecules display concentration trends that scale with disease severity and might serve as prognostic markers for fatal events. Metabolomics evidence is then used as input data for a sex-specific multi-organ metabolic model. This reconstruction provides a comprehensive view of the impact of COVID-19 on the entire human metabolism. The human (male and female) metabolic network is strongly impacted by the disease to an extent dictated by its severity. A marked metabolic reprogramming at the level of many organs indicates an increase in the generic energetic demand of the organism following infection. Sex-specific modulation of immune response is also suggested.PMID:37943960 | DOI:10.1371/journal.ppat.1011787

PLoS One. 2023 Nov 9;18(11):e0289077. doi: 10.1371/journal.pone.0289077. eCollection 2023.ABSTRACTBACKGROUND: Physical activity (PA) is associated with various health benefits, especially in improving chronic health conditions. However, the metabolic changes in host metabolism in response to PA remain unclear, especially in racially/ethnically diverse populations.OBJECTIVE: This study is to assess the metabolic profiles associated with the frequency of PA in White and African American (AA) men.METHODS: Using the untargeted metabolomics data collected from 698 White and AA participants (mean age: 38.0±8.0, age range: 20-50) from the Louisiana Osteoporosis Study (LOS), we conducted linear regression models to examine metabolites that are associated with PA levels (assessed by self-reported regular exercise frequency levels: 0, 1-2, and ≥3 times per week) in White and AA men, respectively, as well as in the pooled sample. Covariates considered for statistical adjustments included race (only for the pooled sample), age, BMI, waist circumstance, smoking status, and alcohol drinking.RESULTS: Of the 1133 untargeted compounds, we identified 7 metabolites associated with PA levels in the pooled sample after covariate adjustment with a false discovery rate of 0.15. Specifically, compared to participants who did not exercise, those who exercised at a frequency ≥3 times/week showed higher abundances in uracil, orotate, 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (P-16:0/18:1) (GPE), threonate, and glycerate, but lower abundances in salicyluric glucuronide and adenine in the pooled sample. However, in Whites, salicyluric glucuronide and orotate were not significant. Adenine, GPE, and threonate were not significant in AAs. In addition, the seven metabolites were not significantly different between participants who exercised ≥3 times/week and 1-2 times/week, nor significantly different between participants with 1-2 times/week and 0/week in the pooled sample and respective White and AA groups.CONCLUSIONS: Metabolite responses to PA are dose sensitive and may differ between White and AA populations. The identified metabolites may help advance our knowledge of guiding precision PA interventions. Studies with rigorous study designs are warranted to elucidate the relationship between PA and metabolites.PMID:37943870 | DOI:10.1371/journal.pone.0289077

Anal Chem. 2023 Nov 9. doi: 10.1021/acs.analchem.3c02325. Online ahead of print.ABSTRACTMetabolite isomers play diverse and crucial roles in various metabolic processes. However, in untargeted metabolomics analysis, it remains a great challenge to distinguish between the constitutional isomers and enantiomers of amine-containing metabolites due to their similar chemical structures and physicochemical properties. In this work, the triplex stable isotope N-phosphoryl amino acids labeling (SIPAL) is developed to identify and relatively quantify the amine-containing metabolites and their isomers by using chiral phosphorus reagents coupled with high-resolution tandem mass spectroscopy. The constitutional isomers could be effectively distinguished with stereo isomers by using the diagnosis ions in MS/MS spectra. The in-house software MS-Isomerism has been parallelly developed for high-throughput screening and quantification. The proposed strategy enables the unbiased detection and relative quantification of isomers of amine-containing metabolites. Based on the characteristic triplet peaks with SIPAL tags, a total of 854 feature peaks with 154 isomer groups are successfully recognized as amine-containing metabolites in liver cells, in which 37 amine-containing metabolites, including amino acids, polyamines, and small peptides, are found to be significantly different between liver cancer cells and normal cells. Notably, it is the first time to identify S-acetyl-glutathione as an endogenous metabolite in liver cells. The SIPAL strategy could provide spectacular insight into the chemical structures and biological functions of the fascinating amine-containing metabolite isomers. The feasibility of SIPAL in isomeric metabolomics analysis may reach a deeper understanding of the mirror-chemistry in life and further advance the discovery of novel biomarkers for disease diagnosis.PMID:37943818 | DOI:10.1021/acs.analchem.3c02325

Anal Chem. 2023 Nov 9. doi: 10.1021/acs.analchem.3c03277. Online ahead of print.ABSTRACTCarboxylic acids are central metabolites in bioenergetics, signal transduction, and post-translation protein regulation. However, the quantitative analysis of carboxylic acids as an indispensable part of metabolomics is prohibitively challenging, particularly in trace amounts of biosamples. Here we report a diazo-carboxyl/hydroxylamine-ketone double click derivatization method for the sensitive analysis of hydrophilic, low-molecular-weight carboxylic acids. In general, our method renders a 5- to 2000-fold higher response in mass spectrometry along with improved chromatographic separation. With this method, we presented the near-single-cell analysis of carboxylic acid metabolites in 10 mouse egg cells before and after fertilization. Malate, fumarate, and β-hydroxybutyrate were found to decrease after fertilization. We also monitored the isotope labeling kinetics of carboxylic acids inside adherent cells cultured in 96-well plates during drug treatment. Finally, we applied this method to plasma or serum samples (5 μL) collected from mice and humans under pathological and physiological conditions. The double click derivatization method paves a way toward single-cell metabolomics and bedside diagnostics.PMID:37943785 | DOI:10.1021/acs.analchem.3c03277

PLoS One. 2023 Nov 9;18(11):e0294377. doi: 10.1371/journal.pone.0294377. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.1371/journal.pone.0240437.].PMID:37943750 | DOI:10.1371/journal.pone.0294377

EMBO Rep. 2023 Nov 9:e49561. doi: 10.15252/embr.201949561. Online ahead of print.ABSTRACTMultidrug-resistant bacteria present a major threat to public health that urgently requires new drugs or treatment approaches. Here, we conduct integrated proteomic and metabolomics analyses to screen for molecular candidates improving survival of mice infected with Vibrio parahaemolyticus, which indicate that L-Alanine metabolism and phagocytosis are strongly correlated with mouse survival. We also assess the role of L-Alanine in improving mouse survival by in vivo bacterial challenge experiments using various bacteria species, including V. parahaemolyticus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Functional studies demonstrate that exogenous L-Alanine promotes phagocytosis of these multidrug-resistant pathogen species. We reveal that the underlying mechanism involves two events boosted by L-Alanine: TLR4 expression and L-Alanine-enhanced TLR4 signaling via increased biosynthesis and secretion of fatty acids, including palmitate. Palmitate enhances binding of lipopolysaccharide to TLR4, thereby promoting TLR4 dimer formation and endocytosis for subsequent activation of the PI3K/Akt and NF-κB pathways and bacteria phagocytosis. Our data suggest that modulation of the metabolic environment is a plausible approach for combating multidrug-resistant bacteria infection.PMID:37943703 | DOI:10.15252/embr.201949561

OMICS. 2023 Nov 9. doi: 10.1089/omi.2023.0169. Online ahead of print.ABSTRACTThis article explores the progressive integration of -omics methods, including genomics, metabolomics, and proteomics, into sports research, highlighting the development of the concept of "sportomics." We discuss how sportomics can be used to comprehend the multilevel metabolism during exercise in real-life conditions faced by athletes, enabling potential personalized interventions to improve performance and recovery and reduce injuries, all with a minimally invasive approach and reduced time. Sportomics may also support highly personalized investigations, including the implementation of n-of-1 clinical trials and the curation of extensive datasets through long-term follow-up of athletes, enabling tailored interventions for athletes based on their unique physiological responses to different conditions. Beyond its immediate sport-related applications, we delve into the potential of utilizing the sportomics approach to translate Big Data regarding top-level athletes into studying different human diseases, especially with nontargeted analysis. Furthermore, we present how the amalgamation of bioinformatics, artificial intelligence, and integrative computational analysis aids in investigating biochemical pathways, and facilitates the search for various biomarkers. We also highlight how sportomics can offer relevant information about doping control analysis. Overall, sportomics offers a comprehensive approach providing novel insights into human metabolism during metabolic stress, leveraging cutting-edge systems science techniques and technologies.PMID:37943554 | DOI:10.1089/omi.2023.0169

FEBS J. 2023 Nov 9. doi: 10.1111/febs.16996. Online ahead of print.ABSTRACTPhosphatidic acid (PA) is the precursor of most phospholipids like phosphatidylethanolamine, phosphatidylglycerol and cardiolipin. In bacteria, its biosynthesis begins with the acylation of glycerol-3-phosphate to lysophosphatidic acid (LPA), which is further acylated to PA by the PlsC enzyme. Some bacteria, like the plant pathogen Xanthomonas campestris, use a similar pathway to acylate lysophosphatidylcholine to phosphatidylcholine (PC). Previous studies assigned two acyltransferases to PC formation. Here, we set out to study their activity and found a second much more prominent function of these enzymes in LPA to PA conversion. This PlsC-like activity was supported by the functional complementation of a temperature-sensitive plsC-deficient Escherichia coli strain. Biocomputational analysis revealed two further PlsC homologs in X. campestris. The cellular levels of the four PlsC-like proteins varied with respect to growth phase and growth temperature. To address the question whether these enzymes have redundant or specific functions, we purified two recombinant, detergent-solubilized enzymes in their active form, which enabled the first direct biochemical comparison of PlsC isoenzymes from the same organism. Overlapping but not identical acyl acceptor and acyl donor preferences suggest redundant and specialized functions of the X. campestris PlsC enzymes. The altered fatty acid composition in plsC mutant strains further supports the functional differentiation of these enzymes.PMID:37943159 | DOI:10.1111/febs.16996

J Sep Sci. 2023 Nov 9:e2300588. doi: 10.1002/jssc.202300588. Online ahead of print.ABSTRACTMetabolomics is the study of metabolites present in a living system. It is a rapidly growing field aimed at discovering novel compounds, studying biological processes, diagnosing diseases, and ensuring quality of food products. Recently, analysis of natural samples has become important to explore novel bioactive compounds and to study how environment and genetics affect living systems. Various metabolomics techniques, databases, and data analysis tools are available for natural sample metabolomics. However, choosing the right method can be a daunting exercise because natural samples are heterogeneous and require untargeted approaches. This tutorial review aims to compile latest technologies to guide an early-career scientist on natural sample metabolomics. First, different extraction methods and their pros and cons are reviewed. Second, currently available metabolomics databases and data analysis tools are summarized. Next, recent research on metabolomics of milk, honey, and microbial samples is reviewed. Finally, after reviewing latest trends in technologies, a checklist is presented to guide an early-career researcher on how to design a metabolomics project. In conclusion, this review is a comprehensive resource for a researcher planning to conduct their first metabolomics analysis. It is also useful for experienced researchers to update themselves on latest trends in metabolomics. This article is protected by copyright. All rights reserved.PMID:37942863 | DOI:10.1002/jssc.202300588

Front Microbiol. 2023 Oct 24;14:1290746. doi: 10.3389/fmicb.2023.1290746. eCollection 2023.ABSTRACTTuberculous meningitis (TBM) poses a diagnostic challenge, particularly impacting vulnerable populations such as infants and those with untreated HIV. Given the diagnostic intricacies of TBM, there's a pressing need for rapid and reliable diagnostic tools. This review scrutinizes the efficacy of up-and-coming technologies like machine learning in transforming TBM diagnostics and management. Advanced diagnostic technologies like targeted gene sequencing, real-time polymerase chain reaction (RT-PCR), miRNA assays, and metagenomic next-generation sequencing (mNGS) offer promising avenues for early TBM detection. The capabilities of these technologies are further augmented when paired with mass spectrometry, metabolomics, and proteomics, enriching the pool of disease-specific biomarkers. Machine learning algorithms, adept at sifting through voluminous datasets like medical imaging, genomic profiles, and patient histories, are increasingly revealing nuanced disease pathways, thereby elevating diagnostic accuracy and guiding treatment strategies. While these burgeoning technologies offer hope for more precise TBM diagnosis, hurdles remain in terms of their clinical implementation. Future endeavors should zero in on the validation of these tools through prospective studies, critically evaluating their limitations, and outlining protocols for seamless incorporation into established healthcare frameworks. Through this review, we aim to present an exhaustive snapshot of emerging diagnostic modalities in TBM, the current standing of machine learning in meningitis diagnostics, and the challenges and future prospects of converging these domains.PMID:37942080 | PMC:PMC10628659 | DOI:10.3389/fmicb.2023.1290746

iScience. 2023 Oct 12;26(11):108196. doi: 10.1016/j.isci.2023.108196. eCollection 2023 Nov 17.ABSTRACTThe liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids via de novo lipogenesis (DNL) when carbohydrates are abundant. Mitochondrial pyruvate metabolism is thought to play important roles in both gluconeogenesis and DNL. We examined the effects of hepatocyte-specific mitochondrial pyruvate carrier (MPC) deletion on the fasting-refeeding response. Rates of DNL during refeeding were impaired by hepatocyte MPC deletion, but this did not reduce intrahepatic lipid content. During fasting, glycerol is converted to glucose by two pathways; a direct cytosolic pathway and an indirect mitochondrial pathway requiring the MPC. Hepatocyte MPC deletion reduced the incorporation of 13C-glycerol into TCA cycle metabolites, but not into new glucose. Furthermore, suppression of glycerol and alanine metabolism did not affect glucose concentrations in fasted hepatocyte-specific MPC-deficient mice, suggesting multiple layers of redundancy in glycemic control in mice.PMID:37942005 | PMC:PMC10628847 | DOI:10.1016/j.isci.2023.108196

Clin Cosmet Investig Dermatol. 2023 Nov 4;16:3181-3191. doi: 10.2147/CCID.S433280. eCollection 2023.ABSTRACTPURPOSE: Psoriasis is a chronic, multi-system skin disease that can be influenced by immunological, environmental, and genetic factors. Plasma metabolomic analysis can provide a great deal of information on potential diagnostic biomarkers, pathogenesis and personalized treatment. However, the role of metabolites in psoriasis is unknown.PATIENTS AND METHODS: We performed an untargeted metabolomic analysis of plasma based on high-resolution liquid chromatography mass spectrometry from 10 plaque psoriasis patients and 10 healthy controls.RESULTS: A total of 301 differential metabolites were detected, of which 10 metabolites were possible potential biomarkers, including vitamins, amino acids, and lipids. At the same time, KEGG pathway enrichment analysis was performed for all detected differential metabolites, and it was found that protein digestion and absorption, amino acid metabolism and lipid metabolism may be jointly involved in regulating the pathogenesis of psoriasis. In addition, the proteins ESR1, OPRM1 and HSD11B1 were identified as possible potential topical therapeutic targets for psoriasis through analysis of the metabolite-protein interaction network.CONCLUSION: In this study, we identified 10 differential metabolites as possible potential combinatorial biomarkers for the diagnosis of psoriasis. 12 metabolic pathways were significantly enriched that may be closely related to the occurrence and development of psoriasis. Three proteins, ESR1, OPRM1, and HSD11B1, were identified as possible potential therapeutic targets for psoriasis.PMID:37941849 | PMC:PMC10631377 | DOI:10.2147/CCID.S433280