PubMed

Metabolites. 2023 Jul 13;13(7):846. doi: 10.3390/metabo13070846.ABSTRACTThe healthy growth of infants during early life is associated with lifelong consequences. Breastfeeding has positive impacts on reducing obesity risk, which is likely due to the varied components of breast milk, such as N-acetylneuraminic acid (Neu5Ac). However, the effect of breast milk Neu5Ac on infant growth has not been well studied. In this study, targeted metabolomic and metagenomic analyses were performed to illustrate the association between breast milk Neu5Ac and infant growth. Results demonstrated that Neu5Ac was significantly abundant in breast milk from infants with low obesity risk in two independent Chinese cohorts. Neu5Ac from breast milk altered infant gut microbiota and bile acid metabolism, resulting in a distinct fecal bile acid profile in the high-Neu5Ac group, which was characterized by reduced levels of primary bile acids and elevated levels of secondary bile acids. Taurodeoxycholic acid 3-sulfate and taurochenodeoxycholic acid 3-sulfate were correlated with high breast milk Neu5Ac and low obesity risk in infants, and their associations with healthy growth were reproduced in mice colonized with infant-derived microbiota. Parabacteroides might be linked to bile acid metabolism and act as a mediator between Neu5Ac and infant growth. These results showed the gut microbiota-dependent crosstalk between breast milk Neu5Ac and infant growth.PMID:37512553 | DOI:10.3390/metabo13070846

Metabolites. 2023 Jul 13;13(7):844. doi: 10.3390/metabo13070844.ABSTRACTQuantifying metabolites from various biological samples is necessary for the clinical and biomedical translation of metabolomics research. One of the ongoing challenges in biomedical metabolomics studies is the large-scale quantification of targeted metabolites, mainly due to the complexity of biological sample matrices. Furthermore, in LC-MS analysis, the response of compounds is influenced by their physicochemical properties, chromatographic conditions, eluent composition, sample preparation, type of MS ionization source, and analyzer used. To facilitate large-scale metabolite quantification, we evaluated the relative response factor (RRF) approach combined with an integrated analytical and computational workflow. This approach considers a compound's individual response in LC-MS analysis relative to that of a non-endogenous reference compound to correct matrix effects. We created a quantitative LC-MS library using the Skyline/Panorama web platform for data processing and public sharing of data. In this study, we developed and validated a metabolomics method for over 280 standard metabolites and quantified over 90 metabolites. The RRF quantification was validated and compared with conventional external calibration approaches as well as literature reports. The Skyline software environment was adapted for processing such metabolomics data, and the results are shared as a "quantitative chromatogram library" with the Panorama web application. This new workflow was found to be suitable for large-scale quantification of metabolites in human plasma samples. In conclusion, we report a novel quantitative chromatogram library with a targeted data analysis workflow for biomedical metabolomic applications.PMID:37512551 | DOI:10.3390/metabo13070844

Metabolites. 2023 Jul 12;13(7):842. doi: 10.3390/metabo13070842.ABSTRACTIn recent years, the FAIR guiding principles and the broader concept of open science has grown in importance in academic research, especially as funding entities have aggressively promoted public sharing of research products. Key to public research sharing is deposition of datasets into online data repositories, but it can be a chore to transform messy unstructured data into the forms required by these repositories. To help generate Metabolomics Workbench depositions, we have developed the MESSES (Metadata from Experimental SpreadSheets Extraction System) software package, implemented in the Python 3 programming language and supported on Linux, Windows, and Mac operating systems. MESSES helps transform tabular data from multiple sources into a Metabolomics Workbench specific deposition format. The package provides three commands, extract, validate, and convert, that implement a natural data transformation workflow. Moreover, MESSES facilitates richer metadata capture than is typically attempted by manual efforts. The source code and extensive documentation is hosted on GitHub and is also available on the Python Package Index for easy installation.PMID:37512549 | DOI:10.3390/metabo13070842

Metabolites. 2023 Jul 11;13(7):838. doi: 10.3390/metabo13070838.ABSTRACTThe development of new tools for assessing the health of cultured shellfish larvae is crucial for aquaculture industries to develop and refine hatchery methodologies. We established a large-volume ecotoxicology/health stressor trial, exposing mussel (Perna canaliculus) embryos to copper in the presence of ethylenediaminetetraacetic acid (EDTA). GC/MS-based metabolomics was applied to identify potential biomarkers for monitoring embryonic/larval health and to characterise mechanisms of metal toxicity. Cellular viability, developmental abnormalities, larval behaviour, mortality, and a targeted analysis of proteins involved in the regulation of reactive oxygen species were simultaneously evaluated to provide a complementary framework for interpretative purposes and authenticate the metabolomics data. Trace metal analysis and speciation modelling verified EDTA as an effective copper chelator. Toxicity thresholds for P. canaliculus were low, with 10% developmental abnormalities in D-stage larvae being recorded upon exposure to 1.10 μg·L-1 bioavailable copper for 66 h. Sublethal levels of bioavailable copper (0.04 and 1.10 μg·L-1) caused coordinated fluctuations in metabolite profiles, which were dependent on development stage, treatment level, and exposure duration. Larvae appeared to successfully employ various mechanisms involving the biosynthesis of antioxidants and a restructuring of energy-related metabolism to alleviate the toxic effects of copper on cells and developing tissues. These results suggest that regulation of trace metal-induced toxicity is tightly linked with metabolism during the early ontogenic development of marine mussels. Lethal-level bioavailable copper (50.3 μg·L-1) caused severe metabolic dysregulation after 3 h of exposure, which worsened with time, substantially delayed embryonic development, induced critical oxidative damage, initiated the apoptotic pathway, and resulted in cell/organism death shortly after 18 h of exposure. Metabolite profiling is a useful approach to (1) assess the health status of marine invertebrate embryos and larvae, (2) detect early warning biomarkers for trace metal contamination, and (3) identify novel regulatory mechanisms of copper-induced toxicity.PMID:37512545 | DOI:10.3390/metabo13070838

Metabolites. 2023 Jul 11;13(7):837. doi: 10.3390/metabo13070837.ABSTRACTBreath volatile organic compound (VOC) analysis is a non-invasive tool for assessing health status; the compositional profile of these compounds in the breath of patients with chronic kidney disease is believed to change with decreasing renal function. We aimed to identify breath VOCs for recognizing patients with chronic kidney disease. Using thermal desorption-gas chromatography/mass spectrometry, untargeted analysis of breath markers was performed using breath samples of healthy controls (n = 18) versus non-dialysis (n = 21) and hemodialysis (n = 12) patients with chronic kidney disease in this cross-sectional study. A total of 303 VOCs alongside 12 clinical variables were used to determine the breath VOC profile. Metabolomic analysis revealed that age, systolic blood pressure, and fifty-eight breath VOCs differed significantly between the chronic kidney disease group (non-dialysis + hemodialysis) and healthy controls. Thirty-six VOCs and two clinical variables that showed significant associations with chronic kidney disease in the univariate analysis were further analyzed. Different spectra of breath volatile organic compounds between the control and chronic kidney disease groups were obtained. A multivariate model incorporating age, 2-methyl-pentane, and cyclohexanone showed high performance (accuracy, 86%) in identifying patients with chronic kidney disease with odds ratios of 0.18 (95% CI, 0.07-2.49, p = 0.013); 2.10 (0.94-2.24, p = 0.025); and 2.31 (0.88-2.64, p = 0.008), respectively. Hence, this study showed that renal dysfunction induces a characteristic profile of breath VOCs that can be used as non-invasive potential biomarkers in screening tests for CKD.PMID:37512544 | DOI:10.3390/metabo13070837

Metabolites. 2023 Jul 11;13(7):836. doi: 10.3390/metabo13070836.ABSTRACTMyostatin (MSTN) is a negative regulator of skeletal muscle genesis during development. MSTN mutation leads to increased lean meat production and reduced fat deposition in livestock. However, the mechanism by which MSTN promotes myogenesis by regulating metabolism is not clear. In this study, we compared the metabolomics of the livers of wild-type (WT) and MSTN mutation cattle (MT), and found changes in the content and proportion of fatty acids and bile acids in MT cattle. The differential metabolites were enriched in sterol synthesis and primary bile acid synthesis. We further analyzed the expression of genes involved in the regulation of lipid and bile acid metabolism, and found that the loss of MSTN may alter lipid synthesis and bile acid metabolism. This study provides new basic data for MSTN mutations in beef cattle breeding.PMID:37512543 | DOI:10.3390/metabo13070836

Metabolites. 2023 Jul 10;13(7):833. doi: 10.3390/metabo13070833.ABSTRACTLittle is known about the metabolic differences between endurance and strength athletes in comparison with sedentary subjects under controlled conditions and about variation of the metabolome throughout one year. We hypothesized that (1) the resting metabolic profile differs between sedentary subjects and athletes and between perennially endurance- and strength-trained athletes and (2) varies throughout one year of training. We performed quantitative, targeted metabolomics (Biocrates MxP® Quant 500, Biocrates Life Sciences AG, Innsbruck, Austria) in plasma samples at rest in three groups of male adults, 12 strength-trained (weightlifters, 20 ± 3 years), 10 endurance-trained athletes (runners, 24 ± 3 years), and 12 sedentary subjects (25 ± 4 years) at the end of three training phases (regeneration, preparation, and competition) within one training year. Performance and anthropometric data showed significant (p < 0.05) differences between the groups. Metabolomic analysis revealed different resting metabolic profiles between the groups with acetylcarnitines, di- and triacylglycerols, and glycerophospho- and sphingolipids, as well as several amino acids as the most robust metabolites. Furthermore, we observed changes in free carnitine and 3-methylhistidine in strength-trained athletes throughout the training year. Regular endurance or strength training induces changes in the concentration of several metabolites associated with adaptations of the mitochondrial energy and glycolytic metabolism with concomitant changes in amino acid metabolism and cell signaling.PMID:37512540 | DOI:10.3390/metabo13070833

Metabolites. 2023 Jul 7;13(7):828. doi: 10.3390/metabo13070828.ABSTRACTThe metabolic profiles of human feces are influenced by various genetic and environmental factors, which makes feces an attractive biosample for numerous applications, including the early detection of gut diseases. However, feces is complex, heterogeneous, and dynamic with a significant live bacterial biomass. With such challenges, stool metabolomics has been understudied compared to other biospecimens, and there is a current lack of consensus on methods to collect, prepare, and analyze feces. One of the critical steps required to accelerate the field is having a metabolomics stool reference material available. Fecal samples are generally presented in two major forms: fecal water and lyophilized feces. In this study, two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS) was used as an analytical platform to characterize pooled human feces, provided by the National Institute of Standards and Technology (NIST) as Research-Grade Test Materials. The collected fecal samples were derived from eight healthy individuals with two different diets: vegans and omnivores, matched by age, sex, and body mass index (BMI), and stored as fecal water and lyophilized feces. Various data analysis strategies were presented to determine the differences in the fecal metabolomic profiles. The results indicate that the sample storage condition has a major influence on the metabolic profiles of feces such that the impact from storage surpasses the metabolic differences from the diet types. The findings of the current study would contribute towards the development of a stool reference material.PMID:37512535 | DOI:10.3390/metabo13070828

Metabolites. 2023 Jul 5;13(7):826. doi: 10.3390/metabo13070826.ABSTRACTMetabolomics-based genome-wide association studies (mGWAS) are key to understanding the genetic regulations of metabolites in complex phenotypes. We previously developed mGWAS-Explorer 1.0 to link single-nucleotide polymorphisms (SNPs), metabolites, genes and phenotypes for hypothesis generation. It has become clear that identifying potential causal relationships between metabolites and phenotypes, as well as providing deep functional insights, are crucial for further downstream applications. Here, we introduce mGWAS-Explorer 2.0 to support the causal analysis between >4000 metabolites and various phenotypes. The results can be interpreted within the context of semantic triples and molecular quantitative trait loci (QTL) data. The underlying R package is released for reproducible analysis. Using two case studies, we demonstrate that mGWAS-Explorer 2.0 is able to detect potential causal relationships between arachidonic acid and Crohn's disease, as well as between glycine and coronary heart disease.PMID:37512533 | DOI:10.3390/metabo13070826

Metabolites. 2023 Jul 4;13(7):818. doi: 10.3390/metabo13070818.ABSTRACTDietary modulation of the gut microbiota has recently received considerable attention. It is well established that consumption of berries confers a number of health benefits. We previously reported that a black raspberry (BRB)-rich diet effectively modulates the gut microbiota. Given the role of anthocyanins in the health benefits of berries, coupled with interactions of gut microbial metabolites with host health, the objective of this follow-up study was to further characterize the profile of functional metabolites in the gut microbiome modulated by anthocyanins. We utilized a berry-derived classic anthocyanin, cyanidin-3-glucoside (C3G), combined with a mouse model to probe C3G-associated functional metabolic products of gut bacteria through a mass spectrometry-based metabolomic profiling technique. Results showed that C3G substantially changed the gut microbiota of mice, including its composition and metabolic profile. A distinct metabolic profile in addition to a variety of key microbiota-related metabolites was observed in C3G-treated mice. Microbial metabolites involved in protein digestion and absorption were differently abundant between C3G-treated and control mice, which may be linked to the effects of berry consumption. Results of the present study suggest the involvement of the gut microbiota in the health benefits of C3G, providing evidence connecting the gut microbiota with berry consumption and its beneficial effects.PMID:37512525 | DOI:10.3390/metabo13070818

Metabolites. 2023 Jul 3;13(7):815. doi: 10.3390/metabo13070815.ABSTRACTTemperature is considered to be a major abiotic factor influencing aquatic life. Marine heatwaves are emerging as threats to sustainable shellfish aquaculture, affecting the farming of New Zealand's green-lipped mussel [Perna canaliculus (Gmelin, 1791)]. In this study, P. canaliculus were gradually exposed to high-temperature stress, mimicking a five-day marine heatwave event, to better understand the effects of heat stress on the metabolome of mussels. Following liquid chromatography-tandem mass spectrometry analyses of haemolymph samples, key sugar-based metabolites supported energy production via the glycolysis pathway and TCA cycle by 24 h and 48 h of heat stress. Anaerobic metabolism also fulfilled the role of energy production. Antioxidant molecules acted within thermally stressed mussels to mitigate oxidative stress. Purine metabolism supported tissue protection and energy replenishment. Pyrimidine metabolism supported the protection of nucleic acids and protein synthesis. Amino acids ensured balanced intracellular osmolality at 24 h and ammonia detoxification at 48 h. Altogether, this work provides evidence that P. canaliculus has the potential to adapt to heat stress up to 24 °C by regulating its energy metabolism, balancing nucleotide production, and implementing oxidative stress mechanisms over time. The data reported herein can also be used to evaluate the risks of heatwaves and improve mitigation strategies for aquaculture.PMID:37512522 | DOI:10.3390/metabo13070815

Metabolites. 2023 Jun 29;13(7):809. doi: 10.3390/metabo13070809.ABSTRACTLipidomics analyses of bacteria offer the potential to detect and monitor infections in a host since many bacterial lipids are not present in mammals. To evaluate this omics approach, we first built a database of bacterial lipids for representative Gram-positive and Gram-negative bacteria. Our lipidomics analysis of the reference bacteria involved high-resolution mass spectrometry and electrospray ionization with less than a 1.0 ppm mass error. The lipidomics profiles of bacterial cultures clearly distinguished between Gram-positive and Gram-negative bacteria. In the case of bovine paratuberculosis (PTB) serum, we monitored two unique bacterial lipids that we also monitored in Mycobacterium avian subspecies PTB. These were PDIM-B C82, a phthiodiolone dimycocerosate, and the trehalose monomycolate hTMM 28:1, constituents of the bacterial cell envelope in mycolic-containing bacteria. The next step will be to determine if lipidomics can detect subclinical PTB infections which can last 2-to-4 years in bovine PTB. Our data further suggest that it will be worthwhile to continue building our bacterial lipidomics database and investigate the further utility of this approach in other infections of veterinary and human clinical interest.PMID:37512516 | DOI:10.3390/metabo13070809

Metabolites. 2023 Jun 28;13(7):802. doi: 10.3390/metabo13070802.ABSTRACTHigh-dimensional metabolomics analyses may identify convergent and divergent markers, potentially representing aligned or orthogonal disease pathways that underly conditions such as pulmonary arterial hypertension (PAH). Using a comprehensive PAH metabolomics dataset, we applied six different conventional and statistical learning techniques to identify analytes associated with key outcomes and compared the results. We found that certain conventional techniques, such as Bonferroni/FDR correction, prioritized metabolites that tended to be highly intercorrelated. Statistical learning techniques generally agreed with conventional techniques on the top-ranked metabolites, but were also more inclusive of different metabolite groups. In particular, conventional methods prioritized sterol and oxylipin metabolites in relation to idiopathic versus non-idiopathic PAH, whereas statistical learning methods tended to prioritize eicosanoid, bile acid, fatty acid, and fatty acyl ester metabolites. Our findings demonstrate how conventional and statistical learning techniques can offer both concordant or discordant results. In the case of a rare yet morbid condition, such as PAH, convergent metabolites may reflect common pathways to shared disease outcomes whereas divergent metabolites could signal either distinct etiologic mechanisms, different sub-phenotypes, or varying stages of disease progression. Notwithstanding the need to investigate the mechanisms underlying the observed results, our main findings suggest that a multi-method approach to statistical analyses of high-dimensional human metabolomics datasets could effectively broaden the scientific yield from a given study design.PMID:37512509 | DOI:10.3390/metabo13070802

Toxins (Basel). 2023 Jul 5;15(7):446. doi: 10.3390/toxins15070446.ABSTRACTTrichothecenes are the most common Fusarium toxins detected in grains and related products. Type A trichothecenes are among the mycotoxins of greatest concern to food and feed safety due to their high toxicity. Recently, two different trichothecene genotypes within Fusarium species were reported. The available information showed that Tri1 and Tri16 genes are the key determinants of the trichothecene profiles of T-2 and DAS genotypes. In this review, polymorphisms in the Tri1 and Tri16 genes in the two genotypes were investigated. Meanwhile, the functions of genes involved in DAS and NEO biosynthesis are discussed. The possible biosynthetic pathways of DAS and NEO are proposed in this review, which will facilitate the understanding of the synthesis process of trichothecenes in Fusarium strains and may also inspire researchers to design and conduct further research. Together, the review provides insight into trichothecene profile differentiation and Tri gene evolutionary processes responsible for the structural diversification of trichothecene produced by Fusarium.PMID:37505715 | DOI:10.3390/toxins15070446

Physiol Behav. 2023 Jul 26:114305. doi: 10.1016/j.physbeh.2023.114305. Online ahead of print.ABSTRACTA trend toward earlier pubertal maturation in both sexes has been shown in many countries. Early puberty affects an increasing proportion of children for reasons that remain obscure. Novel candidate biomarkers are strongly needed. We sought to apply untargeted metabolomic profiling to identify triggering mechanisms and candidate biomarkers in children with early puberty. Participants aged 7 - 12 years old were recruited directly from two elementary schools of Bengbu, Anhui Province, China, from Feb 2021 to May 2021. Early puberty was determined by breast and testicular development at baseline (May 2021) and 6-month later. Ultra-high-performance liquid chromatography-based untargeted metabolomic profiling was performed on urine samples of children with early puberty and control subjects. Metabolomic profiling for early puberty in a sex dependent manner. For boys, we identified several perturbed pathways, including histidine metabolism, glycine, serine and threonine metabolism, and selenoamino acid metabolism, associated with early puberty. In contrast, there were differences in pyruvate metabolism, one carbon pool by folate, and D-glutamine and D-glutamate metabolism pathways in girls with early puberty compared with controls. In addition, 4-hydroxyhippuric acid and 5-methoxytryptophol were shown as potential independent diagnostic biomarker for early puberty in boys, 3-hydroxybenzoic acid and glutaminylproline were shown as early biomarker for early puberty in girls, achieving area under the ROC curve of 0.71 and 0.72 in discriminating early puberty boys, and 0.70 and 0.74 in discriminating early puberty girls from controls. Through metabolomic analysis, we have identified metabolic perturbations and potential biomarkers of early puberty.PMID:37507079 | DOI:10.1016/j.physbeh.2023.114305

Sci Total Environ. 2023 Jul 26:165821. doi: 10.1016/j.scitotenv.2023.165821. Online ahead of print.ABSTRACTHuman exposure to arsenic via drinking water is one of globally concerned health issues. Oxidative stress is regarded as the denominator of arsenic-inducing toxicities. Therefore, to identify intracellular source of reactive oxygen species (ROS) could be essential for addressing the detrimental effects of arsenite (iAsIII). In this study, the contributions of different pathways to ROS formation in iAsIII-treated human normal liver cells (L-02) were quantitatively assessed, and then concomitant oxidative impairs were evaluated using metabolomics and lipidomics approaches. Following iAsIII treatment, NADPH oxidase (NOX) activity and expression levels of p47phox and p67phox were upregulated, and NOX-derived ROS contributed to almost 60.0 % of the total ROS. Moreover, iAsIII also induced mitochondrial superoxide anion and impaired mitochondrial respiratory function of L-02 cells with a decreasing ATP production. The inhibition of NOX activity significantly rescued mitochondrial membrane potential in iAsIII-treated L-02 cells. Purine and glycerophospholipids metabolisms in L-02 cells were disrupted by iAsIII, which might be used to represent DNA and plasma membrane damages, respectively. Our study supported that NOX could be the primary pathway of ROS overproduction and revealed the potential mechanisms of iAsIII toxicity related to oxidative stress.PMID:37506919 | DOI:10.1016/j.scitotenv.2023.165821

Food Chem Toxicol. 2023 Jul 26:113971. doi: 10.1016/j.fct.2023.113971. Online ahead of print.ABSTRACTObesity is one of the major metabolic syndrome risk factors upon which altered metabolic pathways follow. This study aimed to discern altered metabolic pathways associated with obesity and to pinpoint metabolite biomarkers in serum of obese rats fed on high fructose diet using metabolomics. Further, the effect of standardized green versus black caffeinated aqueous extracts (tea and coffee) in controlling obesity and its comorbidities through monitoring relevant serum biomarkers viz. Leptin, adiponectin, spexin, malondialdehyde, total antioxidant capacity. Liver tissue oxidative stress (catalase, super oxide dismutase and glutathione) and inflammation (IL-1β and IL-6) markers were assessed for green coffee and its mixture with green tea. Results revealed improvement of all parameters upon treatments with more prominence for those treated with green caffeinated extract (coffee and tea) especially in mixture. Upon comparing with obese rat group, the green mixture of coffee and tea exhibited anti-hyperlipidemic action through lowering serum triglycerides by 35.0% and elevating high density lipoprotein by 71.0%. Black tea was likewise effective in lowering serum cholesterol and low density lipoprotein by 28.0 and 50.6%, respectively. GC-MS- based metabolomics of rat serum led to the identification of 34 metabolites with obese rat serum enriched in fatty acids (oleamide).PMID:37506863 | DOI:10.1016/j.fct.2023.113971

Cell Signal. 2023 Jul 26:110829. doi: 10.1016/j.cellsig.2023.110829. Online ahead of print.ABSTRACTPURPOSE: Osteosarcoma is one of the leading causes of cancer mortality in children and teenagers. Dysregulation of lipid metabolism has been reported to involve tumor progression. Our previous evidence has revealed that circular RNA hsa_circ_0000073 enhanced the proliferation and metastasis of osteosarcoma cells. However, the effect of hsa_circ_0000073 on the lipid metabolism of osteosarcoma remains unclear. In this paper, we focused on the effect of hsa_circ_0000073 in lipid metabolism and investigated a network among hsa_circ_0000073/ miR-1184 /FADS2 in osteosarcoma, which provides a new idea to treat osteosarcoma.METHODS: The osteosarcoma and its adjacent tissue samples were collected for further validation. qRT-PCR or western blot was employed to detect the expression of hsa_circ_0000073, miR-1184, and FADS2 in OS cells and tissues. Microarray analysis, mass spectrometry, metabolomics analysis, and bioinformatics analysis were used to explore the potential function and target gene of hsa_circ_0000073. Oil red o, Nile red staining, and Triglyceride content assay were adopted to confirm the effect of hsa_circ_0000073 on the lipid metabolism of OS. Dual-luciferase reporter assays and RNA immunoprecipitation were applied to construct and validate the ceRNA network of hsa_circ_0000073. The xenograft mouse model was taken to verify the effect of hsa_circ_0000073 on lipid metabolism in vivo.RESULTS: The results confirmed that hsa_circ_0000073 was raised in the tumor tissues more than its adjacent tissue. Moreover, the higher expression of hsa_circ_0000073 was associated with worse survival rates, advanced clinical stage, large tumor size, and metastasis. After hsa_circ_0000073 silence, the gene chip and metabolomics result implied that hsa_circ_0000073 expression is positively correlated with a 91 genes signature and 78 metabolites in MG-63 and Saos-2 cells. The bioinformatics analysis indicated that hsa_circ_0000073 might involve in the biological processes of lipid metabolism. Further loss and gain of function experiments affirmed that hsa_circ_0000073 could impact cell lipid synthesis. Mechanically, hsa_circ_0000073 favored the expression of FADS2 genes by sponging miR-1184. Consistent with these observations, silencing of hsa_circ_0000073 inhibited lipid synthesis in vivo xenograft mouse model.CONCLUSIONS: Our study revealed that hsa_circ_0000073 contributed to the lipid synthesis of osteosarcoma by decreasing the expression of miR-1184, thereby increasing FADS2, which provides new insights into treating osteosarcoma.PMID:37506860 | DOI:10.1016/j.cellsig.2023.110829

Environ Pollut. 2023 Jul 26:122238. doi: 10.1016/j.envpol.2023.122238. Online ahead of print.ABSTRACTCeftriaxone is an emerging contaminant due to its potential harm, while its effects on liver are still need to be clarified. In this study, we first pretreated the 8-week-old C57BL/6J mice with high dose ceftriaxone sodium (Cef, 400 mg/mL, 0.2 mL per dose) for 8 days to prepare a gut dysbiosis model, then treated with normal feed for a two-month recovery period, and applied non-targeted metabolomics (including lipidomics) to investigate the variations of fecal and liver metabolome, and coupled with targeted determination of fecal short-chain fatty acids (SCFAs) and bile acids (BAs). Lastly, the correlations and mediation analysis between the liver metabolism and gut metabolism/microbes were carried, and the potential mechanisms of the mal-effects on gut-liver axis induced by Cef pretreatment were accordingly discussed. Compared to the control group, Cef pretreatment reduced the rate of weight gain and hepatosomatic index, induced bile duct epithelial cells proliferated around the central vein and appearance of binucleated hepatocytes, decreased the ratio of total branching chains amino acids (BCAAs) to total aromatic amino acids (AAAs) in liver metabolome. In fecal metabolome, the total fecal SCFAs and BAs did not change significantly while butyric acid decreased and the primary BAs increased after Cef pretreatment. Correlation and mediation analysis revealed one potential mechanism that Cef may first change the intestinal microbiota (such as destroying its normal structure, reducing its abundance and the stability of the microbial network or certain microbe abundance like Alistipes), and then change the intestinal metabolism (such as acetate, caproate, propionate), leading to liver metabolic disorder (such as spermidine, inosine, cinnamaldehyde). This study proved the possibility of Cef-induced liver damage, displayed the overall metabolic profile of the liver following Cef pretreatment and provided a theoretical framework for further research into the mechanism of Cef-induced liver damage.PMID:37506808 | DOI:10.1016/j.envpol.2023.122238

Int J Biol Macromol. 2023 Jul 26:126025. doi: 10.1016/j.ijbiomac.2023.126025. Online ahead of print.ABSTRACTIntramuscular fat content is closely related to the quality of beef, where the forkhead box protein O1 (FOXO1) is involved in adipocyte differentiation and lipid metabolism, but the specific mechanism of its involvement is still unclear. In this study, interfering with FOXO1 promoted the G1/S transformation of bovine adipocytes by enhancing the expression of proliferation marker genes PCNA, CDK1, CDK2, CCNA2, CCNB1, and CCNE2, thereby positively regulating the proliferation of bovine adipocytes. Additionally, interfering with FOXO1 negatively regulated the expression of adipogenic differentiation marker genes PPARG and CEBPA, as well as lipid anabolism marker genes ACC, FASN, SCD1, SREBP1, FABP4, ACSL1, LPL, and DGAT1, thus reducing triglyceride (TG) content and inhibiting the generation of lipid droplets in bovine adipocytes. A combination of transcriptomic and metabolomics analyses revealed that FOXO1 could regulate the lipogenesis of cattle by influencing the AMPK and PI3K/AKT pathways. Importantly, chromatin immunoprecipitation (ChIP) and site-directed mutagenesis revealed that FOXO1 could regulate bovine lipogenesis by binding to the promoter regions of the CD36 and STEAP4 genes and affecting their transcriptional activities. These results provide a foundation for studying the role and molecular mechanism of FOXO1 in the bovine adipogenesis.PMID:37506793 | DOI:10.1016/j.ijbiomac.2023.126025