PubMed

Sci Total Environ. 2023 Sep 14:167039. doi: 10.1016/j.scitotenv.2023.167039. Online ahead of print.ABSTRACTCadmium (Cd), a predominant environmental pollutant, is a canonical toxicant that acts on the kidneys. However, the nephrotoxic effect and underlying mechanism activated by chronic exposure to Cd remain unclear. In the present study, male mice (C57BL/6J, 8 weeks) were treated with 0.6 mg/L cadmium chloride (CdCl2) administered orally for 6 months, and tubular epithelial cells (TCMK-1 cells) were treated with low-dose (1, 2, and 3 μM) CdCl2 for 72 h (h). Our study results revealed that environmental Cd exposure triggered ferroptosis and renal dysfunction. Spatially resolved metabolomics enabled delineation of metabolic profiles and visualization of the disruption to glutathione homeostasis related to ferroptosis in mouse kidneys. Multiomics analysis revealed that chronic Cd exposure induced glutathione redox imbalance that depended on STEAP3-driven lysosomal iron overload. In particular, glutathione metabolic reprogramming linked to ferroptosis emerged as a metabolic hallmark in the blood of Cd-exposed workers. In conclusion, this study provides the first evidence indicating that chronic Cd exposure triggers ferroptosis and renal dysfunction that depend on STEAP3-mediated glutathione redox imbalance, greatly increasing our understanding of the metabolic reprogramming induced by Cd exposure in the kidneys and providing novel clues linking chronic Cd exposure to nephrotoxicity.PMID:37716689 | DOI:10.1016/j.scitotenv.2023.167039

Int J Biol Macromol. 2023 Sep 14:126860. doi: 10.1016/j.ijbiomac.2023.126860. Online ahead of print.ABSTRACTAtractylodes chinensis (DC.) Koidz. polysaccharide (AKP) has been shown to have hypoglycemic activity. In this study, the effects of AKP on fecal microbiota and metabolites in healthy subjects and patients with type 2 diabetes mellitus (T2DM) were investigated using an in vitro simulated digestive fermentation model. AKP were isolated and purified from Atractylodes chinensis (DC.) Koidz. Its main component AKP1 (AKP-0 M, about 78 % of AKP) has an average molecular weight of 3.25 kDa with monosaccharide composition of rhamnose, arabinose, and galactosamine in a molar ratio of 1: 1.25: 2.88. Notably, AKP fermentation might improve the intestinal microbiota of T2DM patients by the enrichment of some specific bacteria rather than the increase of microbial diversity. The addition of AKP specifically enriched Bifidobacteriaceae and weakened the proportion of Escherichia-Shigella. Moreover, AKP also increased the levels of short-chain fatty acids without affecting total gut gas production, suggesting that AKP could have beneficial effects while avoiding flatulence. Metabolomic analysis revealed that ARP fermentation caused changes in some metabolites, which were mainly related to energy metabolism and amino acid metabolism. Importantly, ARP fermentation significantly increased the level of myo-inositol, an insulin sensitizer. In addition, a significant correlation was observed between specific microbiota and differential metabolites. This study has laid a theoretical foundation for AKP application in functional foods.PMID:37716665 | DOI:10.1016/j.ijbiomac.2023.126860

Int J Biol Macromol. 2023 Sep 14:126831. doi: 10.1016/j.ijbiomac.2023.126831. Online ahead of print.ABSTRACTThe variety of species can be efficiently increased by interspecific hybridization. However, because the males in the hybrid progeny are usually sterile, this heterosis cannot be employed when other cattle and yaks are hybridized. While some system-level studies have sought to explore the etiological basis for male cattle-yak sterility, no systematic cellular analyses of this phenomenon have yet been performed. Here, single-cell RNA sequencing and UPHLC-MS/MS targeted metabolomics methods were used to study the differences in testicular tissue between 4-year-old male yak and 4-year-old male cattle-yak, providing new and comprehensive insights into the causes of male cattle-yak sterility. Cattle-yak testes samples detected 6 somatic cell types and one mixed germ cell type. Comparisons of these cell types revealed the more significant differences in Sertoli cells (SCs) and [Leydig cells and myoid cells (LCs_MCs)] between yak and cattle-yak samples compared to other somatic cell clusters. Even though the LCs and MCs from yaks and cattle-yaks were derived from the differentiation of the same progenitor cells, a high degree of overlap between LCs and MCs was observed in yak samples. Still, only a small overlap between LCs and MCs was observed in cattle-yak samples. Functional enrichment analyses revealed that genes down-regulated in cattle-yak SCs were primarily enriched in biological activity, whereas up-regulated genes in these cells were enriched for apoptotic activity. Furthermore, the genes of up-regulated in LCs_MCs of cattle-yak were significantly enriched in enzyme inhibitor and molecular function inhibitor activity. On the other hand, the genes of down-regulated in these cells were enriched for signal receptor binding, molecular function regulation, positive regulation of biological processes, and regulation of cell communication activity. The most significant annotated differences between yak and cattle-yak LCs_MCs were associated with cell-to-cell communication. While yak LCs_MCs regulated spermatogenic cells at spermatogonia, spermatocyte, and spermatid levels, no such relationships were found between cattle-yak LCs_MCs and germ cells. This may suggest that the somatic niche in male cattle-yak testes is a microenvironment that is ultimately not favorable for spermatogenesis.PMID:37716658 | DOI:10.1016/j.ijbiomac.2023.126831

Chemosphere. 2023 Sep 14:140189. doi: 10.1016/j.chemosphere.2023.140189. Online ahead of print.ABSTRACTCadmium sulfide nanomaterials are of great concern because of their potential toxicity and unavoidable releases due to multiple commercial applications of nanoparticles (NPs). Commercial NPs act as mediators of damage to plant cells and pose potential toxicity to plants and human health. In the current study, investigated the phytotoxicology, absorption, translocation, antioxidant enzyme activity, and metabolic profiles of maize (Zea mays L.) seedlings exposed to different hydroponic treatments for fifteen days. The different concentrations of CdS NPs (3, 15, 30, 50, and 100 mg/L), 0.3 mg/L Cd ions, and unexposed control were performed in treatments. The results indicated that CdS NPs could present phytotoxic effects on seed germination and root elongation. Compared to the control, the CdS NPs dramatically reduced the shoots and root biomass, as well as the shape of the roots. Transmission electron microscopy and energy-dispersive mapping confirmed that CdS NPs could penetrate the maize root epidermis and bioaccumulate in the shoots with high concentrations. According to metabolomics studies, exposure to CdS NPs and Cd ions would result in metabolic disruption. Based on the statistical analysis, 290 out of 336 metabolites (86.30%) were obviously inhibited. The findings of this study demonstrated possible risks of emerging potential toxic NPs, and the release of these NPs to environment is a serious concern for agricultural activities.PMID:37716569 | DOI:10.1016/j.chemosphere.2023.140189

Phytochemistry. 2023 Sep 15:113854. doi: 10.1016/j.phytochem.2023.113854. Online ahead of print.ABSTRACTMany people in developing countries rely on herbal remedies for their primary healthcare needs. The challenge however is that several of these products lack proper documentation of quality and safety. To ensure consistent quality, validated methods are needed to establish and control quality attributes associated with identity, purity, and levels of bioactive constituents of the respective herbal materials. The present study focused on Phyllanthus urinaria (PU), a widely used medicinal plant in Ghana and West Africa that lacks the necessary quality control standards. The study aimed to develop an HPTLC identification method, which together with UPLC-ESI-Q-TOF-MS/MS analysis established the identity of PU samples and differentiated PU from other closely related Phyllanthus species. Quantitative UPLC and HPTLC methods were developed to assess the contents of selected active markers in the PU samples, which invariably led to the proposal of acceptance criteria for the active markers. Prior to the content analyses, the sample extraction procedure was optimized through the use of Design of Experiment method. The effects of harvest time and geographic origin on the content of active compounds were demonstrated in the investigations. PU samples were also found to be contaminated with higher levels of pesticides like chlorpyrifos and folpet. Essentially, this study provides analytical protocols, insights into the quality status of PU samples in Ghana, and analytical specifications contained in a drafted monograph for future consideration in regional and subregional African pharmacopoeias.PMID:37716546 | DOI:10.1016/j.phytochem.2023.113854

Cancer Lett. 2023 Sep 14:216384. doi: 10.1016/j.canlet.2023.216384. Online ahead of print.ABSTRACTThere are well demonstrated differences in tumor cell metabolism between right sided (RCC) and left sided (LCC) colon cancer, which could underlie the robust differences observed in their clinical behavior, particularly in metastatic disease. As such, we utilized liquid chromatography-mass spectrometry to perform an untargeted metabolomics analysis comparing frozen liver metastasis (LM) biobank samples derived from patients with RCC (N = 32) and LCC (N = 58) to further elucidate the unique biology of each. We also performed an untargeted RNA-seq and subsequent network analysis on samples derived from an overlapping subset of patients (RCC: N = 10; LCC: N = 18). Our biobank redemonstrates the inferior survival of patients with RCC-derived LM (P = 0.04), a well-established finding. Our metabolomic results demonstrate the increase of reactive oxygen species associated metabolites and bile acids in RCC. Conversely, carnitines, indicators of fatty acid oxidation, were relatively increased in LCC. The transcriptomic analysis implicated increased MEK-ERK, PI3K-AKT and Transcription Growth Factor Beta signaling in RCC LM. Our multi-omic analysis reveals several key differences in cellular physiology which taken together may be relevant to clinical differences in tumor behavior between RCC and LCC liver metastasis.PMID:37716465 | DOI:10.1016/j.canlet.2023.216384

Chem Biol Interact. 2023 Sep 14:110714. doi: 10.1016/j.cbi.2023.110714. Online ahead of print.ABSTRACTColon cancer is the third leading cause of cancer death globally. Although early screenings and advances in treatments have reduced mortality since 1970, identification of novel targets for therapeutic intervention is needed to address tumor heterogeneity and recurrence. Previous work identified aldehyde dehydrogenase 1B1 (ALDH1B1) as a critical factor in colon tumorigenesis. To investigate further, we utilized a human colon adenocarcinoma cell line (SW480) in which the ALDH1B1 protein expression has been knocked down by 80% via shRNA. Through multi-omics (transcriptomics, proteomics, and untargeted metabolomics) analysis, we identified the impact of ALDH1B1 knocking down (KD) on molecular signatures in colon cancer cells. Suppression of ALDH1B1 expression resulted in 357 differentially expressed genes (DEGs), 191 differentially expressed proteins (DEPs) and 891 differentially altered metabolites (DAMs). Functional annotation and enrichment analyses revealed that: (1) DEGs were enriched in integrin-linked kinase (ILK) signaling and growth and development pathways; (2) DEPs were mainly involved in apoptosis signaling and cellular stress response pathways; and (3) DAMs were associated with biosynthesis, intercellular and second messenger signaling. Collectively, the present study provides new molecular information associated with the cellular functions of ALDH1B1, which helps to direct future investigation of colon cancer.PMID:37716420 | DOI:10.1016/j.cbi.2023.110714

Osteoarthritis Cartilage. 2023 Sep 14:S1063-4584(23)00916-0. doi: 10.1016/j.joca.2023.09.004. Online ahead of print.ABSTRACTOBJECTIVE: Osteoarthritis is a heterogeneous disease. The objective was to compare differences in underlying cellular mechanisms and endogenous repair pathways between synovial fluid from male and female participants with different injuries to improve current understanding of the pathophysiology of downstream post-traumatic osteoarthritis.DESIGN: Synovial fluid from n=33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. Synovial fluid was extracted and analyzed via liquid chromatography-mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies (ligament, meniscal, and combined ligament and meniscal) and patient sex. Samples were pooled and underwent secondary fragmentation to identify metabolites.RESULTS: Different knee injuries uniquely altered synovial fluid metabolites and downstream pathways including amino acid, lipid, and inflammatory-associated metabolic pathways. Notably, sexual dimorphic metabolic phenotypes were examined between males and females and within injury pathology. Cervonyl carnitine and other identified metabolites differed in concentrations between sexes.CONCLUSIONS: These results suggest that different injuries and patient sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries, sex, and post-traumatic osteoarthritis development may yield data regarding how endogenous repair pathways differ between male and female injury types. Ongoing metabolomic analysis of synovial fluid in injured male and female patients can be performed to monitor post-traumatic osteoarthritis development and progression.PMID:37716406 | DOI:10.1016/j.joca.2023.09.004

Environ Int. 2023 Sep 9;180:108198. doi: 10.1016/j.envint.2023.108198. Online ahead of print.ABSTRACTBACKGROUND: Exposures to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), environmentally persistent chemicals detectable in the blood of most Americans, have been associated with several health outcomes. To offer insight into their possible biologic effects, we evaluated the metabolomic correlates of circulating PFOS and PFOA among 3,647 participants in eight nested case-control serum metabolomic profiling studies from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.METHODS: Metabolomic profiling was conducted by Metabolon Inc., using ultra high-performance liquid chromatography/tandem accurate mass spectrometry. We conducted study-specific multivariable linear regression analyses estimating the associations of metabolite levels with levels of PFOS or PFOA. For metabolites measured in at least 3 of 8 nested case-control studies, random effects meta-analysis was used to summarize study-specific results (1,038 metabolites in PFOS analyses and 1,100 in PFOA analyses).RESULTS: The meta-analysis identified 51 and 38 metabolites associated with PFOS and PFOA, respectively, at a Bonferroni-corrected significance level (4.8x10-5 and 4.6x10-5, respectively). For both PFOS and PFOA, the most common types of associated metabolites were lipids (sphingolipids, fatty acid metabolites) and xenobiotics (xanthine metabolites, chemicals). Positive associations were commonly observed with lipid metabolites sphingomyelin (d18:1/18:0) (P = 2.0x10-10 and 2.0x10-8, respectively), 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (P = 2.7x10-15, 1.1x10-17), and lignoceroylcarnitine (C24) (P = 2.6x10-8, 6.2x10-6). The strongest positive associations were observed for chemicals 3,5-dichloro-2,6-dihydroxybenzoic acid (P = 3.0x10-112 and 6.8x10-13, respectively) and 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (P = 1.6x10-14, 2.3x10-6). Other metabolites positively associated with PFOS included D-glucose (carbohydrate), carotene diol (vitamin A metabolism), and L-alpha-aminobutyric acid (glutathione metabolism), while uric acid (purine metabolite) was positively associated with PFOA. PFOS associations were consistent even after adjusting for PFOA as a covariate, while PFOA associations were greatly attenuated with PFOS adjustment.CONCLUSIONS: In this large metabolomic study, we observed robust positive associations with PFOS for several molecules. Further investigation of these metabolites may offer insight into PFOS-related biologic effects.PMID:37716341 | DOI:10.1016/j.envint.2023.108198

Nutr Res. 2023 Aug 24;119:33-42. doi: 10.1016/j.nutres.2023.08.009. Online ahead of print.ABSTRACTDiabetic foot (DF) is one of the serious chronic complications of diabetes. Accurate prediction of the risk of DF may take timely intervention measures to prevent its occurrence. The understanding of metabolomic changes in the progression of diabetes to DF may reveal new targets for interventions. We hypothesized that changes in metabolic pathways during DF would lead to changes in the metabolic profile, which could be predictive signature specific to it. In the present study, 43 participants with type 2 diabetes mellitus (T2DM), 32 T2DM participants with DF (T2DM-F), and 36 healthy subjects were enrolled and their serum samples were used for targeted and nonpolar metabolic analysis with liquid chromatography-tandem mass spectrometry. Differential metabolites related to T2DM-F were discovered in metabolomic analysis. Lasso machine learning regression model, random forest algorithm, causal mediation analysis, disease risk assessment, and clinical decision model were carried out. T2DM and T2DM-F groups could be distinguished with the healthy control group. The differential metabolites were all enriched in alpha-linolenic acid and linoleic acid metabolic pathways including arachidonic acid, docosapentaenoic-acid 22N-6, and docosahexaenoic-acid, which were significantly lower in the T2DM and T2DM-F groups compared with the healthy control group. The differential metabolites in T2DM-F vs T2DM groups were enriched to branched-chain amino acid (BCAA) catabolic pathways involving in methylmalonic acid, succinic acid, 3-methyl-2-oxovaleric acid, and ketoleucine, which were the BCAA catabolic intermediates and significantly lower in the T2DM-F compared with the T2DM group except for succinic acid. We reveal a new set of predictive signatures and associate the lower BCAA catabolic intermediates with the progression from T2DM to T2DM-F.PMID:37716292 | DOI:10.1016/j.nutres.2023.08.009

J Pharm Biomed Anal. 2023 Sep 12;236:115717. doi: 10.1016/j.jpba.2023.115717. Online ahead of print.ABSTRACTAs is well documented, Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Meanwhile, Schisandra polysaccharide (SCP) has been reported to exert a protective effect on the nervous system and can regulate metabolic disorders in AD-like symptoms of amyloid β-peptide (Aβ) 25-35-induced rats. Nevertheless, the underlying mechanisms and metabolic markers for the diagnosis of AD are yet to be determined. This study aimed to explore the neuroprotective effect and potential mechanism of action of SCP in AD-like symptoms of Aβ25-35-induced rats by combining pharmacodynamics, metabolomics, and lipidomics. The pharmacodynamic results revealed that SCP significantly improved the spatial learning and long-term memory function and the morphology of neurons in the hippocampal CA1 region, alleviated inflammatory damage and oxidative stress, inhibited the activation of microglia and astrocytes, and increased the proportion of mature neurons of AD-like symptoms of Aβ25-35-induced rats. The results of hippocampal metabolomics and serum lipidomics showed 46 and 48 potential biomarkers were identified for the SCP treatment of AD, respectively. The involved pathways principally comprised lipid metabolism, amino acid metabolism, and energy metabolism. This study elucidates the neuroprotective effect of SCP in AD and its mechanism from the perspective of metabolomics and lipidomics and provides a theoretical basis for the therapeutic effect of SCP in AD.PMID:37716276 | DOI:10.1016/j.jpba.2023.115717

J Pharm Biomed Anal. 2023 Sep 14;236:115725. doi: 10.1016/j.jpba.2023.115725. Online ahead of print.ABSTRACTType 2 diabetes mellitus (T2DM) has been the most prevalent disease and has become a serious public health threat worldwide. Gynura bicolor (Willd.) DC. (GB) contains a variety of nutrients and possesses numerous activities, which might benefit those with diabetes. The current study aimed to confirm the improvement of metabolic disorders and explore the potential mechanism of GB in high fat diet-fed (HFD) and streptozotocin (STZ)-induced T2DM mice. The aboveground sample of GB was extracted with alcohol, and identified by highperformance liquid chromatography (HPLC) and liquid chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis. HFD and STZ-induced T2DM mice were administrated with GB extract. Biochemical and histopathologic examinations were conducted, and metabolomics evaluation was performed in serum and urine. GB significantly reduced body weight and liver weight, reversed hyperlipidemia, hyperglycemia, insulin resistance, oxidative stress and inflammation, improved hepatic histopathological changes and lipid deposition and mitigated liver injury in T2DM mice. Serum and urine metabolomics demonstrated a variety of significantly disturbed metabolites in T2DM and these changes were reversed after GB administration, including 13S-hydroxyoctadecadienoic acid, arachidonic acid, L-Valine and so on. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the overlapping enriched pathways in the normal control group and GB group were identified, including linoleic acid metabolism, PPAR signaling pathway, protein digestion and absorption, biosynthesis of amino acids and so on. This study demonstrates that the ethanol extract of GB remarkably attenuates metabolic disorders and maintains the dynamic balance of metabolites in T2DM, providing a scientific basis for GB in the treatment of T2DM and metabolism diseases.PMID:37716275 | DOI:10.1016/j.jpba.2023.115725

J Stroke Cerebrovasc Dis. 2023 Sep 14;32(11):107347. doi: 10.1016/j.jstrokecerebrovasdis.2023.107347. Online ahead of print.ABSTRACTOBJECTIVES: This study was designed to investigate metabolic biomarker changes and related metabolic pathways of Butylphthalide (NBP) on cerebral ischemia/reperfusion.METHODS: In this study, a mouse cerebral ischemia/reperfusion (I/R) model was prepared using the middle cerebral artery occlusion method, and neurobehavioral score and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining experiments were used to confirm the obvious NBP anti-cerebral ischemia effect. The protective effect of NBP in the mouse cerebral I/R model and its metabolic pathway and mechanism were investigated using mouse blood samples.RESULTS: The metabolic profiles of mice in the I/R+NBP, I/R, and sham groups were significantly different. Under the condition that I/R vs. sham was downregulated and I/R + NBP vs. I/R was upregulated, 88 differential metabolites, including estradiol, ubiquinone-2, 2-oxoarginine, and L-histidine trimethylbetaine, were screened and identified. The related metabolic pathways involved arginine and proline metabolism, oxidative phosphorylation, ubiquitin and other terpenoid-quinone biosynthesis, and estrogen signaling.CONCLUSIONS: Metabolomics was used to elucidate the NBP mechanism in cerebral ischemia treatment in mice, revealing synergistic NBP pharmacological characteristics with multiple targets.PMID:37716103 | DOI:10.1016/j.jstrokecerebrovasdis.2023.107347

Plant J. 2023 Sep 16. doi: 10.1111/tpj.16465. Online ahead of print.ABSTRACTTree growth and survival are dependent on their ability to perceive signals, integrate them, and trigger timely and fitted molecular and growth responses. While ectomycorrhizal symbiosis is a predominant tree-microbe interaction in forest ecosystems, little is known about how and to what extent it helps trees cope with environmental changes. We hypothesized that the presence of Laccaria bicolor influences abiotic cue perception by Populus trichocarpa and the ensuing signaling cascade. We submitted ectomycorrhizal or non-ectomycorrhizal P. trichocarpa cuttings to short-term cessation of watering or ozone fumigation to focus on signaling networks before the onset of any physiological damage. Poplar gene expression, metabolite levels, and hormone levels were measured in several organs (roots, leaves, mycorrhizas) and integrated into networks. We discriminated the signal responses modified or maintained by ectomycorrhization. Ectomycorrhizas buffered hormonal changes in response to short-term environmental variations systemically prepared the root system for further fungal colonization and alleviated part of the root abscisic acid (ABA) signaling. The presence of ectomycorrhizas in the roots also modified the leaf multi-omics landscape and ozone responses, most likely through rewiring of the molecular drivers of photosynthesis and the calcium signaling pathway. In conclusion, P. trichocarpa-L. bicolor symbiosis results in a systemic remodeling of the host's signaling networks in response to abiotic changes. In addition, ectomycorrhizal, hormonal, metabolic, and transcriptomic blueprints are maintained in response to abiotic cues, suggesting that ectomycorrhizas are less responsive than non-mycorrhizal roots to abiotic challenges.PMID:37715981 | DOI:10.1111/tpj.16465

CNS Neurosci Ther. 2023 Sep 16. doi: 10.1111/cns.14455. Online ahead of print.ABSTRACTBACKGROUND: Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies.AIMS: In this study, we utilized UPLC-MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics perspective.RESULTS: The behavioral results of our study demonstrate that LUT significantly ameliorated anxiety and depression-like behaviors while enhancing cognitive function in LOD rats. Metabolomic analysis revealed that the effects of LUT on LOD rats were primarily mediated through the glycerophospholipid metabolic pathway in the hippocampus and prefrontal cortex. The levels of key lipid metabolites, phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), in the glycerophospholipid metabolic pathway were significantly altered by LUT treatment, with PC and PE showing significant correlations with behavioral indices. Molecular docking analysis indicated that LUT had strong binding activity with phosphatidylserine synthase 1 (PTDSS1), phosphatidylserine synthase 2 (PTDSS2), and phosphatidylserine decarboxylase (PISD), which are involved in the transformation and synthesis of PC, PE, and PS. Lastly, our study explored the reasons for the opposing trends of PC, PE, and PS in the hippocampus and prefrontal cortex from the perspective of autophagy, which may be attributable to the bidirectional regulation of autophagy in distinct brain regions.CONCLUSIONS: Our results revealed significant alterations in the glycerophospholipid metabolism pathways in both the hippocampus and prefrontal cortex of LOD rats. Moreover, LUT appears to regulate autophagy disorders by specifically modulating glycerophospholipid metabolism in different brain regions of LOD rats, consequently alleviating depression-like behavior in these animals.PMID:37715585 | DOI:10.1111/cns.14455

Endocrinol Diabetes Metab. 2023 Sep 16:e448. doi: 10.1002/edm2.448. Online ahead of print.ABSTRACTOBJECTIVE: Hyperglycaemia in Type 1 diabetes (T1D) results from an absolute insulin deficiency. However, insulin resistance (IR) may exacerbate glycaemic instability in T1D and contribute to long-term cardiovascular complications. We previously showed that IR in teenagers with obesity is associated with sex-dependent derangements in the catabolism of branched-chain amino acids (BCAA) and fatty acids. Here we hypothesized that byproducts of BCAA and fatty acid metabolism may serve as biomarkers or determinants of glycaemic control and IR in prepubertal or early pubertal children with T1D.METHODS: Metabolites, hormones and cytokines from fasting blood samples were analysed in 28 children (15 females, 13 males; age 6-11 years) with T1D. Principal components analysis (PCA) and multiple linear regression models were used to correlate metabolites of interest with glycaemic control, total daily insulin dose (TDD, units/kg/d), adiponectin and the triglyceride (TG) to high-density lipoprotein (HDL) ratio.RESULTS: Males and females were comparable in age, BMI-z, insulin sensitivity, glycaemic control, inflammatory markers, BCAAs and C2/C3/C5-acylcarnitines. The majority of components retained in PCA were related to fatty acid oxidation (FAO) and BCAA catabolism. HbA1c correlated positively with Factor 2 (acylcarnitines, incomplete FAO) and Factor 9 (fasting glucose). TDD correlated negatively with C3 and C5 and Factor 10 (BCAA catabolism) and positively with the ratio of C2 to C3 + C5 and Factor 9 (fasting glucose).CONCLUSIONS: These findings suggest that glucose intolerance in prepubertal or early pubertal children with T1D is accompanied by incomplete FAO while TDD is associated with preferential catabolism of fats relative to amino acids.PMID:37715520 | DOI:10.1002/edm2.448

J Diabetes Investig. 2023 Sep 15. doi: 10.1111/jdi.14085. Online ahead of print.ABSTRACTMitochondrial dysfunction causes maternally inherited deafness and diabetes (MIDD). Herein, we report improved glycemic control in a 47-year-old Japanese woman with MIDD using imeglimin without major adverse effects. Biochemical tests and metabolome analysis were performed before and after imeglimin administration. Blood glucose level fluctuations were determined. Sulfonylureas, dipeptidyl peptidase-4 inhibitors (DPP4is), and sodium glucose transporter-2 inhibitors (SGLT2i) were administered to evaluate the efficacy of their combination with imeglimin. Imeglimin decreased the HbA1c and ammonia levels and increased the time-in-range, C-peptide reactivity, and glucagon level. Elevated citrulline and histamine levels were decreased by imeglimin. The hypoglycemic effect was not enhanced by imeglimin when combined with sulfonylurea or DPP4i, but the blood glucose level was improved when combined with SGLT2i. Imeglimin improved glucose concentration-dependent insulin secretion and maximized the insulin secretory capacity by improving mitochondrial function and glutamine metabolism and urea circuit abnormalities by promoting glucagon secretion. Imeglimin could improve glycemic control in MIDD.PMID:37715448 | DOI:10.1111/jdi.14085

Insect Sci. 2023 Sep 15. doi: 10.1111/1744-7917.13272. Online ahead of print.ABSTRACTBody color polyphenism is common in Diaphorina citri. Previous studies compared physiological characteristics in D. citri, but the ecological and biological significance of its body color polyphenism remains poorly understood. We studied the ecological and molecular effects of stressors related to body color in D. citri. Crowding or low temperature induced a high proportion of gray morphs, which had smaller bodies, lower body weight, and greater susceptibility to the insecticide dinotefuran. We performed transcriptomic and metabolomics analysiis of 2 color morphs in D. citri. Gene expression dynamics revealed that the differentially expressed genes were predominantly involved in energy metabolism, including fatty acid metabolism, amino acid metabolism, and carbohydrate metabolism. Among these genes, plexin, glycosidase, phospholipase, take out, trypsin, and triacylglycerol lipase were differentially expressed in 2 color morphs, and 6 hsps (3 hsp70, hsp83, hsp90, hsp68) were upregulated in gray morphs. The metabolome data showed that blue morphs exhibited a higher abundance of fatty acid and amino acid, whereas the content of carbohydrates was elevated in gray morphs. This study partly explains the body color polyphenism of D. citri and provides insights into the molecular changes of stress response of D. citri.PMID:37715371 | DOI:10.1111/1744-7917.13272

Nutr Metab (Lond). 2023 Sep 15;20(1):41. doi: 10.1186/s12986-023-00754-z.ABSTRACTBACKGROUND: Dietary intake during early life may be a modifying factor for cardiometabolic risk (CMR). Metabolomic profiling may enable more precise identification of CMR in adolescence than traditional CMR scores. We aim to assess and compare the prospective associations between an obesogenic dietary pattern (DP) score at age 13 years with a novel vs. traditional CMR score in adolescence and young adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC).METHODS: Study participants were ALSPAC children with diet diary data at age 13. The obesogenic DP z-score, characterized by high energy-density, high % of energy from total fat and free sugars, and low fibre density, was previously derived using reduced rank regression. CMR scores were calculated by combining novel metabolites or traditional risk factors (fat mass index, insulin resistance, mean arterial blood pressure, triacylglycerol, HDL and LDL cholesterol) at age 15 (n = 1808), 17 (n = 1629), and 24 years (n = 1760). Multivariable linear regression models estimated associations of DP z-score with log-transformed CMR z-scores.RESULTS: Compared to the lowest tertile, the highest DP z-score tertile at age 13 was associated with an increase in the metabolomics CMR z-score at age 15 (β = 0.20, 95% CI 0.09, 0.32, p trend < 0.001) and at age 17 (β = 0.22, 95% CI 0.10, 0.34, p trend < 0.001), and with the traditional CMR z-score at age 15 (β = 0.15, 95% CI 0.05, 0.24, p trend 0.020). There was no evidence of an association at age 17 for the traditional CMR z-score (β = 0.07, 95% CI -0.03, 0.16, p trend 0.137) or for both scores at age 24.CONCLUSIONS: An obesogenic DP was associated with greater CMR in adolescents. Stronger associations were observed with a novel metabolite CMR score compared to traditional risk factors. There may be benefits from modifying diet during adolescence for CMR health, which should be prioritized for further research in trials.PMID:37715209 | DOI:10.1186/s12986-023-00754-z

Plant Cell Rep. 2023 Sep 16. doi: 10.1007/s00299-023-03053-2. Online ahead of print.ABSTRACTDose effects of Rf1 gene regulated retrieval mechanism of pollen fertility for CMS-D2 cotton. Cytoplasmic male sterility conditioned by Gossypium harknessii cytoplasm (CMS-D2) is an economical pollination control system for producing hybrid cotton seeds compared to artificial and chemical emasculation methods. However, the unstable restoring ability of restorer lines is a main barrier in the large-scale application of "three-line" hybrid cotton in China. Our phenotypic investigation determined that the homozygous Rf1Rf1 allelic genotype had a stronger ability to generate fertile pollen than the heterozygous Rf1rf1 allelic genotype. To decipher the genetic mechanisms that control the differential levels of pollen fertility, an integrated metabolomic and transcriptomic analysis was performed at two environments using pollen grains of four cotton genotypes differing in Rf1 alleles or cytoplasm. Totally 5,391 differential metabolite features were detected, and 369 specific differential metabolites (DMs) were identified between homozygous and heterozygous Rf1 allelic genotypes with CMS-D2 cytoplasm. In addition, transcriptome analysis identified 2,490 differentially expressed genes (DEGs) and 96 unique hub DEGs with dynamic regulation in this comparative combination. Further integrated analyses revealed that several key DEGs and DMs involved in indole biosynthesis, flavonoid biosynthesis, and sugar metabolism had strong network linkage with fertility restoration. In vitro application of auxin analogue NAA and inhibitor Auxinole confirmed that over-activated auxin signaling might inhibit pollen development, whereas suppressing auxin signaling partially promoted pollen development in CMS-D2 cotton. Our results provide new insight into how the dosage effects of the Rf1 gene regulate pollen fertility of CMS-D2 cotton.PMID:37715064 | DOI:10.1007/s00299-023-03053-2