PubMed

Biotechnol Bioeng. 2023 Nov 22. doi: 10.1002/bit.28599. Online ahead of print.ABSTRACTFermentation monitoring is a powerful tool for bioprocess development and optimization. On-line metabolomics is a technology that is starting to gain attention as a bioprocess monitoring tool, allowing the direct measurement of many compounds in the fermentation broth at a very high time resolution. In this work, targeted on-line metabolomics was used to monitor 40 metabolites of interest during three Escherichia coli succinate production fermentation experiments every 5 min with a triple quadrupole mass spectrometer. This allowed capturing high-time resolution biological data that can provide critical information for process optimization. For nine of these metabolites, simple univariate regression models were used to model compound concentration from their on-line mass spectrometry peak area. These on-line metabolomics univariate models performed comparably to vibrational spectroscopy multivariate partial least squares regressions models reported in the literature, which typically are much more complex and time consuming to build. In conclusion, this work shows how on-line metabolomics can be used to directly monitor many bioprocess compounds of interest and obtain rich biological and bioprocess data.PMID:37990977 | DOI:10.1002/bit.28599

Dis Model Mech. 2023 Nov 22:dmm.049861. doi: 10.1242/dmm.049861. Online ahead of print.ABSTRACTNeurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by germline mutations in the NF1 gene. Children with NF1 are prone to the development of multiple nervous system abnormalities, including autism and brain tumors, which could reflect the effect of NF1 mutation on microglia function. Using heterozygous Nf1-mutant mice, we previously demonstrated that impaired purinergic signaling underlies deficits in microglia process extension and phagocytosis in situ. To determine whether these abnormalities are also observed in human microglia in the setting of NF1, we leveraged an engineered isogenic series of human induced pluripotent stem cells to generate human microglia-like (hiMGL) cells heterozygous for three different NF1 patient-derived NF1 gene mutations. While all NF1-mutant and isogenic control hiMGL cells expressed classical microglia markers and exhibited similar transcriptomes and cytokine/chemokine release profiles, only NF1-mutant hiMGL cells had defects in P2X receptor activation, phagocytosis and motility. Taken together, heterozygous NF1 mutation impairs a subset of human microglia functional properties, which could contribute to the neurological abnormalities seen in children with NF1.PMID:37990867 | DOI:10.1242/dmm.049861

Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231217992. doi: 10.1177/09603271231217992.ABSTRACTBackground: Adipose tissue is a dynamic endocrine organ that plays a key role in regulating metabolic homeostasis. Previous studies confirmed that bisphenol A (BPA) or fructose can interfere with the function of adipose tissue. Nonetheless, knowledge on how exposure to BPA and fructose impacts energy metabolism in adipose tissue remains limited.Purpose: To determine impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue.Method: 57 energy metabolic intermediates in adipose tissue and 7 adipocytokines in serum from Sprague Dawley rats were examined after combined exposure to two levels of BPA (lower dose: 0.25, and higher dose: 25 μg/kg every other day) and 5% fructose for 6 months.Results: combined exposure to lower-dose BPA and fructose significantly increased omentin-1, pyruvic acid, adenosine triphosphate (ATP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and l-lactate; however, these parameters were not significantly affected by higher-dose BPA combined with fructose. Interestingly, the level of succinate (an intermediate of the citric acid cycle) increased dose-dependently in adipose tissue, and the level of apelin 13 (a versatile adipocytokine) decreased dose-dependently in serum after combined exposure to BPA and fructose. Phosphoenolpyruvic acid, phenyl-lactate, and ornithine were significantly correlated with asprosin, omentin-1, apelin, apelin 13, and adiponectin, while l-tyrosine was significantly correlated with irisin and a-FABP under combined exposure to BPA and fructose.Conclusions: these findings indicated that lower-dose BPA combined with fructose could amplify the impact on glycolysis, energy storage, and purine nucleotide biosynthesis in adipose tissue, and adipocytokines, such as omentin-1 and apelin 13, may be related to metabolic interference induced by BPA and fructose exposure.PMID:37990541 | DOI:10.1177/09603271231217992

Mol Nutr Food Res. 2023 Nov 21:e2200842. doi: 10.1002/mnfr.202200842. Online ahead of print.ABSTRACTSCOPE: Consuming goat milk is known to benefit high-fat diet-fed and streptozocin (STZ)-induced diabetic rats, but the underlying mechanisms are unknown. This study is conducted to investigate the metabolic effects of a goat milk diet (a form of goat milk powder) on glucose homeostasis and pancreatic conditions in a mouse model of Type 2 diabetes mellitus (T2DM) induced by STZ.METHODS AND RESULTS: T2DM mice are fed with a goat-milk-based diet containing 10.3% w/w goat milk powder for 10 weeks for investigating the in vivo effects; a β-cell line MIN6 cells are used to test the in vitro effects of digested goat milk (DGM). Goat milk diet improves the deleterious effects of STZ on fasting glucose levels and glucose tolerance, accelerates pancreatic structure recovery, and alters blood metabolites in mice. Based on the significant differences observed in metabolites, the key pathways, metabolite regulatory enzymes, metabolite molecular modules, and biochemical reactions are identified as critical integrated pathways. DGM promotes the cell activity, glucose transportation, and AKT activation in cultured STZ-treated MIN6 cells in vitro.CONCLUSIONS: Goat milk diet improves glucose homeostasis and pancreatic conditions of T2DM mice, in association with improved blood metabolite profiles and activation of pancreatic AKT pathway.PMID:37990402 | DOI:10.1002/mnfr.202200842

Nutr Metab (Lond). 2023 Nov 21;20(1):50. doi: 10.1186/s12986-023-00769-6.ABSTRACTBACKGROUND: This study investigated the effect of uteroplacental insufficiency (UPI) on renal development by detecting metabolic alterations in the kidneys of rats with intrauterine growth restriction (IUGR).METHODS: On gestational day 17, pregnant Sprague Dawley rats were selected and allocated randomly to either the IUGR group or the control group. The IUGR group received a protocol involving the closure of bilateral uterine vessels, while the control group underwent a sham surgery. The rat pups were delivered on gestational day 22 by natural means. Pups were randomly recruited from both the control and IUGR groups on the seventh day after birth. The kidneys were surgically removed to conduct Western blot and metabolomic analyses.RESULTS: IUGR was produced by UPI, as evidenced by the significantly lower body weights of the pups with IUGR compared to the control pups on postnatal day 7. UPI significantly increased the levels of cleaved caspase-3 (p < 0.05) and BAX/Bcl-2 (p < 0.01) in the pups with IUGR. Ten metabolites exhibited statistically significant differences between the groups (q < 0.05). Metabolic pathway enrichment analysis demonstrated statistically significant variations between the groups in the metabolism related to fructose and mannose, amino and nucleotide sugars, and inositol phosphate.CONCLUSIONS: UPI alters kidney metabolism in growth-restricted newborn rats and induces renal apoptosis. The results of our study have the potential to provide new insights into biomarkers and metabolic pathways that are involved in the kidney changes generated by IUGR.PMID:37990266 | DOI:10.1186/s12986-023-00769-6

Plant Methods. 2023 Nov 21;19(1):130. doi: 10.1186/s13007-023-01105-y.ABSTRACTPlant metabolomics is an important research area in plant science. Chemometrics is a useful tool for plant metabolomic data analysis and processing. Among them, high-order chemometrics represented by tensor modeling provides a new and promising technical method for the analysis of complex multi-way plant metabolomics data. This paper systematically reviews different tensor methods widely applied to the analysis of complex plant metabolomic data. The advantages and disadvantages as well as the latest methodological advances of tensor models are reviewed and summarized. At the same time, application of different tensor methods in solving plant science problems are also reviewed and discussed. The reviewed applications of tensor methods in plant metabolomics cover a wide range of important plant science topics including plant gene mutation and phenotype, plant disease and resistance, plant pharmacology and nutrition analysis, and plant products ingredient characterization and quality evaluation. It is evident from the review that tensor methods significantly promote the automated and intelligent process of plant metabolomics analysis and profoundly affect the paradigm of plant science research. To the best of our knowledge, this is the first review to systematically summarize the tensor analysis methods in plant metabolomic data analysis.PMID:37990220 | DOI:10.1186/s13007-023-01105-y

BMC Vet Res. 2023 Nov 21;19(1):242. doi: 10.1186/s12917-023-03806-x.ABSTRACTBACKGROUND: Salmonella Enteritidis is a zoonotic pathogen and poses a substantial risk to human health, as well as significant financial losses to the livestock and poultry industries. It is currently urgent to identify alternatives to antibiotic treatment.RESULTS: In this study, we explored the influence of Puerarin on the immunological response, intestinal flora, serum metabolome, and growth performance of chicks infected with Salmonella Enteritidis. Chicks were weighed at specific time points and the average daily gain (ADG) was calculated. Serum, intestinal, and cecal content samples were collected on days 10 and 17. The results showed that 100 mg/kg of Puerarin significantly suppressed inflammation and enhanced immune function. Metabolomic analysis showed significant differences in serum metabolites after Puerarin treatment and suggested that Puerarin may regulate abnormal amino acid and lipid metabolism after Salmonella Enteritidis infection through the autophagic and ABC transporter pathways. In addition, Puerarin suppressed Salmonella Enteritidis-induced intestinal flora dysbiosis through modulation of the microbial community structures (increased Lactobacillus, Faecalibacterium, and Subdoligranulum), as demonstrated by 16S rRNA analysis.CONCLUSIONS: In conclusion, Puerarin can improve growth performance in chicks, suppress the inflammatory response in vivo, enhance immunity, and regulate lipid and amino acid metabolism and the intestinal flora.PMID:37990191 | DOI:10.1186/s12917-023-03806-x

Sci Rep. 2023 Nov 21;13(1):20351. doi: 10.1038/s41598-023-47750-0.ABSTRACTThe antimicrobial properties of garlic are widely known, and numerous studies confirmed its ability to inhibit the growth of Mycobacterium tuberculosis. In this work, we explored the molecular mechanism of action of sulphides present in garlic essential oil against mycobacteria. The targeted transcriptomics and untargeted LC-MS metabolomics were applied to study dose- and time-dependent metabolic changes in bacterial cells under the influence of stressing agent. Expression profiles of genes coding stress-responsive sigma factors regulatory network and metabolic observations proved that sulphides from garlic essential oil are an efficient and specific agent affecting glycerophospholipids levels and their distribution within the cell envelope. Additionally, sulphides induced the Dimroth rearrangement of 1-Tuberculosinyladenosine to N6-tuberculosinyladenosine in mycobacterial cells as a possible neutralization mechanism protecting the cell from a basic nucleophilic environment. Sulphides affected cell envelope lipids and formation of N6-tuberculosinyladenosine in M. tuberculosis.PMID:37990133 | DOI:10.1038/s41598-023-47750-0

Sci Rep. 2023 Nov 21;13(1):20325. doi: 10.1038/s41598-023-47800-7.ABSTRACTPrimary glomerulonephritis diseases (PGDs) are known as the top causes of chronic kidney disease worldwide. Renal biopsy, an invasive method, is the main approach to diagnose PGDs. Studying the metabolome profiles of kidney diseases is an inclusive approach to identify the disease's underlying pathways and discover novel non-invasive biomarkers. So far, different experiments have explored the metabolome profiles in different PGDs, but the inconsistencies might hinder their clinical translations. The main goal of this meta-analysis study was to achieve consensus panels of dysregulated metabolites in PGD sub-types. The PGDs-related metabolome profiles from urine samples in humans were selected in a comprehensive search. Amanida package in R software was utilized for performing the meta-analysis. Through sub-type analyses, the consensus list of metabolites in each category was obtained. To identify the most affected pathways, functional enrichment analysis was performed. Also, a gene-metabolite network was constructed to identify the key metabolites and their connected proteins. After a vigorous search, among the 11 selected studies (15 metabolite profiles), 270 dysregulated metabolites were recognized in urine of 1154 PGDs and control samples. Through sub-type analyses by Amanida package, the consensus list of metabolites in each category was obtained. Top dysregulated metabolites (vote score of ≥ 4 or ≤ - 4) in PGDs urines were selected as main panel of meta-metabolites including glucose, leucine, choline, betaine, dimethylamine, fumaric acid, citric acid, 3-hydroxyisovaleric acid, pyruvic acid, isobutyric acid, and hippuric acid. The enrichment analyses results revealed the involvement of different biological pathways such as the TCA cycle and amino acid metabolisms in the pathogenesis of PGDs. The constructed metabolite-gene interaction network revealed the high centralities of several metabolites, including pyruvic acid, leucine, and choline. The identified metabolite panels could shed a light on the underlying pathological pathways and be considered as non-invasive biomarkers for the diagnosis of PGD sub-types.PMID:37990116 | DOI:10.1038/s41598-023-47800-7

Sci Rep. 2023 Nov 21;13(1):20365. doi: 10.1038/s41598-023-47657-w.ABSTRACTAbscisic acid (ABA) has been shown to mitigate the deleterious effects of abiotic stresses and to regulate plant growth and development. Salinity is one of the important abiotic stresses affecting plant cell metabolism and physiology, which causes serious damages to crops. In this study, we investigated the protective role of exogenous ABA on leaves in response to salinity stress using rice seedlings (two leaf-one heart) subjected to three treatments: ZCK (control), ZS (50 mM NaCl), and ZSA (5 mg L-1 ABA + 50 mM NaCl). We carried out transcriptomic and metabolomic analyses to identify the molecular mechanisms by which ABA protects plants against salt stress. Results showed that 1159 differentially expressed genes (DEGs) (916 up-regulated, 243 down-regulated) and 63 differentially accumulated metabolites (DAMs) (42 up-regulated, 21 down-regulated) were identified between the ZS and ZSA treatments, respectively. In addition, ABA pretreatment regulated the expression pattern of genes responsible for oxidation redox, starch and sucrose metabolism, and phenylpropanoid biosynthesis. The combined transcriptomic and metabolomic analysis revealed that 16 DEGs and 2 DAMs were involved in Flavonoid biosynthesis and 8 DEGs and 2 DAMs were involved alpha-Linolenic acid metabolism which are responsible for salinity stress tolerance through induced by exogenous ABA. Overall, ABA could enhance rice leaves growth and development mainly by regulating flavonoid biosynthesis and linoleic acid metabolism pathway.PMID:37990109 | DOI:10.1038/s41598-023-47657-w

Nat Commun. 2023 Nov 21;14(1):6763. doi: 10.1038/s41467-023-42424-x.ABSTRACTCholine is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1IEC-KO) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1IEC-KO mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction.PMID:37990006 | DOI:10.1038/s41467-023-42424-x

NPJ Aging. 2023 Nov 21;9(1):28. doi: 10.1038/s41514-023-00124-2.ABSTRACTGlaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.PMID:37990002 | DOI:10.1038/s41514-023-00124-2

Metabolomics. 2023 Nov 21;19(12):96. doi: 10.1007/s11306-023-02061-3.ABSTRACTINTRODUCTION: Plastics used in everyday materials accumulate as waste in the environment and degrade over time. The impacts of the resulting particulate micro- and nanoplastics on human health remain largely unknown. In pregnant mice, we recently demonstrated that exposure to nanoplastics throughout gestation and during lactation resulted in changes in brain structure detected on MRI. One possible explanation for this abnormal postnatal brain development is altered fetal brain metabolism.OBJECTIVES: To determine the effect of maternal exposure to nanoplastics on fetal brain metabolism.METHODS: Healthy pregnant CD-1 mice were exposed to 50 nm polystyrene nanoplastics at a concentration of 106 ng/L through drinking water during gestation. Fetal brain samples were collected at embryonic day 17.5 (n = 18-21 per group per sex) and snap-frozen in liquid nitrogen. Magic angle spinning nuclear magnetic resonance was used to determine metabolite profiles and their relative concentrations in the fetal brain.RESULTS: The relative concentrations of gamma-aminobutyric acid (GABA), creatine and glucose were found to decrease by 40%, 21% and 30% respectively following maternal nanoplastic exposure when compared to the controls (p < 0.05). The change in relative concentration of asparagine with nanoplastic exposure was dependent on fetal sex (p < 0.005).CONCLUSION: Maternal exposure to polystyrene nanoplastics caused abnormal fetal brain metabolism in mice. The present study demonstrates the potential impacts of nanoplastic exposure during fetal development and motivates further studies to evaluate the risk to human pregnancies.PMID:37989919 | DOI:10.1007/s11306-023-02061-3

Food Res Int. 2023 Dec;174(Pt 1):113509. doi: 10.1016/j.foodres.2023.113509. Epub 2023 Sep 23.ABSTRACTThe effects of changes in lipids on the formation of Zn-protoporphyrin (ZnPP) during the processing of Nuodeng ham were analyzed using a lipidomics approach based on UHPLC-MS/MS. The Nuodeng ham samples had a strong fluorescence emission peak at 590 nm, and the fluorescence intensity increased with the processing time. Lipid profiles were mainly affected by processing time. A total of 5 lipid classes were detected, of which glycerophospholipids (GP) and glycerolipids (GL) were the most abundant lipids. Fifty differential lipid compounds were screened, which were mainly GP and GL. Correlation analysis showed that 13 differential lipid compounds were significantly positively correlated with ZnPP content, and they contained more linoleic acid and oleic acid branch chains. Meanwhile, all triglycerides (TG) were negatively correlated with heme content, and they were enriched in stearic acid and palmitic acid branch chains. These findings can deepen the understanding of the relationship between ZnPP and lipids.PMID:37986504 | DOI:10.1016/j.foodres.2023.113509

Food Res Int. 2023 Dec;174(Pt 1):113596. doi: 10.1016/j.foodres.2023.113596. Epub 2023 Oct 15.ABSTRACTThe optimization of processed meats through salt replacement using KCl and k-lactate may reduce the risk of chronic diseases through reduction in dietary sodium. The objective of this study was to investigate the changes and relationships between microbial and lipid metabolism during the fermentation of restructured duck ham with different salt substitutions. Lactobacillus and Staphylococcus were found to be the dominant bacterial species in the 30 % KCl + 70 % NaCl (w/w) and 25 % k-lactate + 75 % NaCl (w/w). The LefSe analysis showed that different biomarkers were present in different ham groups, and the PLS-DA showed that triglycerides (GL) and glycerophospholipids (GP) were the two classes with the highest abundance. Besides, the KEGG pathway analysis revealed that glycerophospholipid metabolism and triglyceride metabolism were also the main metabolic pathways. According to the correlation study, Staphylococcus, Halomonas, and Lactobacillus were mostly linked to the important metabolic pathways in restructured ham. Our findings serve as a foundation for quality assurance and product enhancement for low-salt restructured ham.PMID:37986459 | DOI:10.1016/j.foodres.2023.113596

Sci Rep. 2023 Nov 21;13(1):20385. doi: 10.1038/s41598-023-47558-y.ABSTRACTOxyresveratrol has been documented benefits for neurodegenerative disease. However, the specific molecular mechanisms and pathways involved is currently limited. This study aimed to investigate the potential neuroprotective mechanisms of oxyresveratrol using rotenone-induced human neuroblastoma SH-SY5Y cytotoxicity. Cells were divided into the following groups: control, rotenone, and oxyresveratrol pre-treated before being exposed to rotenone. Cellular assays were performed to investigate neuroprotective effects of oxyresveratrol. The results showed that 20 μM oxyresveratrol was effective in preventing rotenone-induced cell death and decreasing ROS levels in the cells. The alteration of metabolites and pathways involved in the neuroprotective activities of oxyresveratrol were further investigated using LC-QTOF-MS/MS untargeted metabolomics approach. We hypothesized that oxyresveratrol's neuroprotective effects would be associated with neurodegenerative pathways. A total of 294 metabolites were identified. 7,8-dihydrobiopterin exhibited the highest VIP scores (VIP > 3.0; p < 0.05), thus considered a biomarker in this study. Our results demonstrated that pretreatment with oxyresveratrol upregulated the level of 7,8-dihydrobiopterin compared to the positive control. Pathway analysis verified that 7,8-dihydrobiopterin was primarily associated with phenylalanine, tyrosine, and tryptophan metabolism (impact = 1, p < 0.001), serving as essential cofactors for enzymatic function in the dopamine biosynthesis pathway. In conclusion, oxyresveratrol may be benefit for the prevention of neurodegenerative diseases by increasing 7,8-dihydrobiopterin concentration.PMID:37989867 | DOI:10.1038/s41598-023-47558-y

Nat Commun. 2023 Nov 21;14(1):7572. doi: 10.1038/s41467-023-43378-w.ABSTRACTPatients with polycystic kidney disease (PKD) encounter a high risk of clear cell renal cell carcinoma (ccRCC), a malignant tumor with dysregulated lipid metabolism. SET domain-containing 2 (SETD2) has been identified as an important tumor suppressor and an immunosuppressor in ccRCC. However, the role of SETD2 in ccRCC generation in PKD remains largely unexplored. Herein, we perform metabolomics, lipidomics, transcriptomics and proteomics within SETD2 loss induced PKD-ccRCC transition mouse model. Our analyses show that SETD2 loss causes extensive metabolic reprogramming events that eventually results in enhanced sphingomyelin biosynthesis and tumorigenesis. Clinical ccRCC patient specimens further confirm the abnormal metabolic reprogramming and sphingomyelin accumulation. Tumor symptom caused by Setd2 knockout is relieved by myriocin, a selective inhibitor of serine-palmitoyl-transferase and sphingomyelin biosynthesis. Our results reveal that SETD2 deficiency promotes large-scale metabolic reprogramming and sphingomyelin biosynthesis during PKD-ccRCC transition. This study introduces high-quality multi-omics resources and uncovers a regulatory mechanism of SETD2 on lipid metabolism during tumorigenesis.PMID:37989747 | DOI:10.1038/s41467-023-43378-w

Cell Death Dis. 2023 Nov 22;14(11):758. doi: 10.1038/s41419-023-06305-x.ABSTRACTAutophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome marker GFP-LC3 in the cytoplasm of cells, as well as the downregulation of its nuclear pool indicative of autophagic flux. In this respect, 3,4-DC showed a broader autophagy-inducing activity than another chalcone (4,4- dimethoxychalcone), spermidine and triethylene tetramine. Thus, we characterized the potential antiatherogenic activity of 3,4-DC in two different mouse models, namely, (i) neointima formation with smooth muscle expansion of vein segments grafted to the carotid artery and (ii) genetically predisposed ApoE-/- mice fed an atherogenic diet. In the vein graft model, local application of 3,4-DC was able to maintain the lumen of vessels and to reduce neointima lesions. In the diet-induced model, intraperitoneal injections of 3,4-DC significantly reduced the number of atherosclerotic lesions in the aorta. In conclusion, 3,4-DC stands out as an autophagy inducer with potent antiatherogenic activity.PMID:37989732 | DOI:10.1038/s41419-023-06305-x

J Sci Food Agric. 2023 Nov 21. doi: 10.1002/jsfa.13127. Online ahead of print.ABSTRACTBACKGROUND: The hyperlipidaemia was characterized by abnormally elevated blood lipids. Quinoa saponins (QS) has multiple pharmacological activities, including antitumor, bactericidal and immune-enhancing. However the lipid-lowering effect and mechanisms of QS in vivo have been scarcely reported.METHODS: The effect of QS against hyperlipidaemia induced by high-fat diet (HFD) in rats was explored based on gut microbiota and serum non-targeted metabolomics.RESULTS: The study demonstrated that the supplementation of QS could reduce serum lipids, body weight, liver injury and inflammation. 16S rRNA sequencing demonstrated that QS mildly increased alpha-diversity, altered the overall structure of intestinal flora, decreased the relative richness of Firmicutes, the ratio of Firmicutes/Bacteroidetes (F/B) (P<0.05) and increased the relative richness of Actinobacteria, Bacteroidetes, Bifidobacterium, Roseburia and Coprococcus (P<0.05). Simultaneously, metabolomics analysis showed that QS altered serum functional metabolites with respect to bile acid biosynthesis, arachidonic acid metabolism, and taurine and hypotaurine metabolism, which were closely related to bile acid metabolism and fatty acid β-oxidation. Furthermore, QS increased protein levels of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase 1 (CPT-1), which were related to the screened metabolic pathways. Spearman correlation analysis showed that there was a correlation between gut microbiota and differential metabolites.CONCLUSION: QS could prevent lipid metabolism disorders in hyperlipidemic rats, which may be closely associated with the regulation of the gut microbiota and multiple metabolic pathways. This study may provide new evidence for QS as a natural active substance for the prevention of hyperlipidaemia. This article is protected by copyright. All rights reserved.PMID:37989713 | DOI:10.1002/jsfa.13127

Endocrinol Metab (Seoul). 2023 Nov 21. doi: 10.3803/EnM.2023.1814. Online ahead of print.ABSTRACTMetabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing's syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing's syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.PMID:37989266 | DOI:10.3803/EnM.2023.1814