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Integrated liver proteomics and metabolomics identify metabolic pathways affected by pantothenic acid deficiency in Pekin ducks

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Animal Nutrition 2022年第4期11卷 1-14页

作者： Jing Tang Yongbao Wu Bo Zhang Suyun Liang Zhanbao Guo Jian Hu Zhengkui Zhou Ming Xie Shuisheng Hou State Key Laboratory of Animal Nutrition Key Laboratory of Animal(Poultry)Genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural Sciences100193BeijingChina

Pantothenic acid deficiency(PAD)in animals causes growth depression,fasting hypoglycemia and impaired lipid and glucose metabolism.However,a systematic multi-omics analysis of effects of PAD on hepatic function has apparently not been reported.We investigated liver proteome and metabolome changes induced by PAD to explain its effects on growth and liver metabolic disorders.Pekin ducks(1-dold,n=128)were allocated into 2 groups,with 8 replicates and 8 birds per replicate.For 16 d,all ducks had ad libitum access to either a PAD or a pantothenic acid adequate(control,CON)diet,formulated by supplementing a basal diet with 0 or 8 mg pantothenic acid/kg of diet,respectively.Liver enlargement,elevated liver glycogen concentrations and decreased liver concentrations of triglyceride and unsaturated fatty acids were present in the PAD group compared to the CON group.Based on integrated liver proteomics and metabolomics,PAD mainly affected glycogen synthesis and degradation,glycolysis and gluconeogenesis,tricarboxylic acid(TCA)cycle,peroxisome proliferator-activated receptor(PPAR)signaling pathway,fatty acid beta oxidation,and oxidative phosphorylation.Selected proteins were confirmed by Western blotting.Downregulation of proteins and metabolites involved in glycogen synthesis and degradation,glycolysis and gluconeogenesis implied that these processes were impaired in PAD ducks,which could have contributed to fasting hypoglycemia,liver glycogen storage,insufficient ATP production,and growth retardation.In contrast,PAD also upregulated proteins and metabolites involved in fatty acid beta oxidation,the TCA cycle,and oxidative phosphorylation processes in the liver;presumably compensatory responses to produce ATP.We inferred that PAD decreased liver triglyceride and unsaturated fatty acids by activating fatty acid beta oxidation and impairing unsaturated fatty acid synthesis.These findings contributed to our understanding of the mechanisms of PAD-induced changes in hepatic metabolism.

关键词： Pantothenic acid Hepatic metabolism Proteomics metabolomics Hypoglycemia

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metabolomics and network pharmacology reveal the mechanism of the Jiawei Yangshen pill in treatment of cyclophosphamide-induced dyszoospermia in mice

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Traditional Medicine Research 2023年第1期8卷 1-11页

作者： Jing-Ning Yan Xiao-Qin Liu Xiang-Long Meng Xiao-Yan Zhang Qi Sheng Bo-Rui Guo Yan Li Kai-Han Li Jia-Dong Chang Clinical College of Traditional Chinese Medicine Shanxi University of Chinese MedicineJinzhong 030619China College of Chinese Materia Medica and Food Engineering Shanxi University of Chinese MedicineJinzhong 030619China Shanxi Key Laboratory of Tradition Herbal Medicines Processing Shanxi University of Chinese MedicineJinzhong 030619China.

Background:The Jiawei Yangshen pill enhances sperm abundance.However,the pharmacological mechanism of action of the Jiawei Yangshen pill remains unclear.This study aimed to explore the therapeutic effect of the Jiawei Yangshen pill in the treatment of dyszoospermia and study the underlying mechanism.Methods:A dyszoospermia model was established by injecting mice with cyclophosphamide(50 mg/kg)consecutively for 7 days.Physiological and pathological indicators of the testis and hormone levels were examined after 4 weeks of treatment.Untargeted metabolomics using high-performance liquid chromatograph-mass spectrometry was performed on testis specimens.Network pharmacology analysis was used to construct an“ingredient-target-disease”interactive network,followed by metabolic pathway enrichment analysis.Western blotting was performed to examine the levels of the related proteins.Results:The Jiawei Yangshen pill significantly increased the testis index,epididymal index,sperm count,and testosterone level,while concurrently decreasing sperm mortality and luteinizing hormone levels.The spermatogenic cells in the Jiawei Yangshen pill-treated mice were well arranged with an increased number.Significantly different metabolites were identified.Western blotting showed that the expression levels of p-anti-adenosine monophosphate-activated protein kinase/anti-adenosine monophosphate-activated protein kinase and p-protein kinase B/protein kinase B were significantly increased after the Jiawei Yangshen pill treatment,whereas the expression levels of transforming growth factor-β1 and nuclear factor kappa B(p65)were remarkably decreased.Conclusion:The Jiawei Yangshen pill significantly improved testicular microcirculatory injury and overall metabolic levels in mice with dyszoospermia.

关键词： Jiawei Yangshen pill dyszoospermia metabolomics network pharmacology

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Developmental toxicity of TCBPA on the nervous and cardiovascular systems of zebrafish (Danio rerio): A combination of transcriptomic and metabolomics

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Journal of Environmental Sciences 2023年第5期127卷 197-209页

作者： Wentao Liu Yifan Pan Lu Yang Yun Xie Xuanyue Chen Jing Chang Weiyu Hao Lifei Zhu Bin Wan Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China Agricultural Information Institute Chinese Academy of Agricultural SciencesBeijing 100081China Institute of Food Safety Chinese Academy of Inspection and QuarantineBeijing 100176China Beijing Academy of Agriculture and Forestry Sciences Beijing 100097China

Tetrachlorobisphenol A(TCBPA),a widely used halogenated flame retardant,is frequently detected in environmental compartments and human samples.However,unknown developmental toxicity and mechanisms limit the entire understanding of its effects.In this study,zebrafish(Danio rerio)embryos were exposed to various concentrations of TCBPA while a combination of transcriptomics,behavioral and biochemical analyzes as well as metabolomics were applied to decipher its toxic effects and the potential mechanisms.We found that TCBPA could interfere with nervous and cardiovascular development through focal adhesion and extracellular matrix-receptor(ECM-receptor)interaction pathways through transcriptomic analysis.Behavioral and biochemical analysis results indicated abnormal swimming behavior of zebrafish larvae.Morphological observations revealed that TCBPA could cause the loss of head blood vessels.Metabolomic analysis showed that arginine-related metabolic pathways were one of the main pathways leading to TCBPA developmental toxicity.Our study demonstrated that by using omics,TCBPA was shown to have neurological and cardiovascular developmental toxicity and the underlying mechanisms were uncovered and major pathways identified.

关键词： Tetrachlorobisphenol A(TCBPA) Zebrafish Developmental toxicity Transcriptomics metabolomics

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Plasma metabolomics identifies metabolic alterations associated with the growth and development of cat

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动物模型与实验医学(英文) 2023年第4期6卷 306-316页

作者： Shuaiyang Liu Yun Chen Xiaoming Wang Shuang Wang Lan Bai Xu Cheng Juan Wan Yufeng Hu Yi Ding Xin Zhang Mingxing Ding Hongliang Li Manli Hu School of Basic Medical Science Wuhan UniversityWuhanChina Institute of Model Animal Wuhan UniversityWuhanChina Clinical Trial Centers Huanggang Central HospitalHuanggangChina College of Veterinary Medicine Huazhong Agricultural UniversityWuhanChina Key Laboratory of Cardiovascular Disease Prevention and Control Ministry of EducationSchool of Basic Medical ScienceGannan Medical UniversityGanzhouChina Gannan Innovation and Translational Medicine Research Institute Gannan Medical UniversityGanzhouChina

Background:The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development.Methods:Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests.Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways.Results:In this study,we found that the red blood cell counts,liver function indexes(albumin and gamma-glutamyl transpeptidase),and the concentration of triglyceride and glucose changed significant with growth and development.The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats.Most of these metabolites belong to major classes of lipids and lipid-like molecules.The most obvious age-related metabolites include reduced levels of chenodeoxycholate,taurocholate,cholate,and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum.These metabolites are mainly involved in the primary bile acid biosynthesis pathway,the bile secretion pathway,and the taurine and hypotaurine metabolism pathway.Conclusion:This study revealed many age-related metabolite alterations in the feline plasma.These age-varying metabolites,especially in the bile acid biosynthesis and secretion metabolism pathways,indicate that the regulation of these pathways is involved in the growth and development of cats.This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.

关键词： bile acids cat growth metabolomics plasma

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UPLC-Q-TOF/MS-based metabolomics reveals modulatory effects of Mesona chinensis Benth polysaccharide in liver injury mice induced by cyclophosphamide

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Food Science and Human Wellness 2023年第2期12卷 584-595页

作者： Yuzhen Hong Mingyue Shen Qiang Yu Yi Chen Jianhua Xie State Key Laboratory of Food Science and Technology Nanchang UniversityNanchang 330047China

The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide(MP)on cyclophosphamide(CTX)induced liver injury in mice.To explore metabolic profile of liver tissue and feces among normal group,CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS.The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids(SCFAs),with the best dose of 200 mg/kg·body weight(bw).The principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLSDA)scores plots of the liver and feces samples showed a clear separation among normal,model and highdose of MP(MPH).There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces,which were mainly involved in 8 metabolic pathways:taurine and hypotaurine metabolism,phenylalanine metabolism,α-linolenic acid metabolism,tricarboxylic acid(TCA)cycle,phenylalanine,tyrosine and tryptophan biosynthesis,arachidonic acid metabolism,sphingolipid metabolism as well as tryptophan metabolism.Moreover,a common metabolite arachidonic acid was observed in liver and feces samples.These endogenous metabolites may be considered to be MP’s response to liver protection.It will help to further understand the mechanism of MP and provide a basis for further research.

关键词： metabolomics Polysaccharide Liver injury Cyclophosphamide

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Chemical diversity of scleractinian corals revealed by untargeted metabolomics and molecular networking

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Acta Oceanologica Sinica 2023年第11期42卷 127-135页

作者： Jiying Pei Yuxia Zhou Shiguo Chen Kefu Yu Zhenjun Qin Ruijie Zhang Yitong Wang Coral Reef Research Center of China Guangxi Laboratory on the Study of Coral Reefs in the South China SeaSchool of Marine SciencesGuangxi UniversityNanning 530000China Southern Marine Science and Engineering Guangdong Laboratory Zhuhai 519080China

The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate intraspecific variation in the metabolites of these corals,the metabolomes of four species(Pocillopora meandrina,Seriatopora hystrix,Acropora formosa,and Fungia fungites)from the South China Sea were analyzed using untargeted mass spectrometry-based metabolomics.The results showed that a variety of metabolites,including amino acids,peptides,lipids,and other small molecules,were differentially distributed among the four species,leading to their significant separation in principal component analysis and hierarchical clustering plots.The higher content of storage lipids in branching corals(P.meandrina,S.hystrix,and A.formosa)compared to the solitary coral(F.fungites)may be due to the high densities of zooxanthellae in their tissues.The high content of aromatic amino acids in P.meandrina may help the coral protect against ultraviolet damage and promote growth in shallow seawater,while nitrogen-rich compounds may enable S.hystrix to survive in various challenging environments.The metabolites enriched in F.fungites,including amino acids,dipeptides,phospholipids,and other small molecules,may be related to the composition of the coral's mucus and its life-history,such as its ability to move freely and live solitarily.Studying the chemical diversity of scleractinian corals not only provides insight into their environmental adaptation,but also holds potential for the chemotaxonomy of corals and the discovery of novel bioactive natural products.

关键词： scleractinian coral chemical diversity metabolomics molecular networking environmental adaptation

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Integrative metabolomics and transcriptomics analyses reveal pivotal regulatory mechanisms of 1-methylcyclopropene in maintaining postharvest storage quality of‘Fuji’apples

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Food Quality and Safety 2023年第1期7卷 49-62页

作者： Lingling Zhang Peiyu Zhang Modi Gao Yi Zhao Chunjiao Zhang Hongliang Zhu College of Food Science and Nutritional Engineering China Agricultural UniversityBeijingChina Supervision Inspection&Testing Center of Agricultural Products QualityMinistry of Agriculture and Rural AffairsBeijingChina

In this study,integrative metabolomics and transcriptomics analyses were conducted to investigate the effects of 1-methylcyclopropene(1-MCP)on apple fruit quality during long-term cold storage.The results showed that 1-MCP(1μL/L)treatment could maintain fruits apparent quality(i.***.external color and firmness),inhibit the increase of rot rate and soluble solids content/titratable acidity ratio,decrease ethylene release,and respiratory intensity during cold storage,and extend shelf life.Moreover,1-MCP had long-term effects on the accumulation of many qualities related to metabolite and gene expression in fruits.1-MCP affected genes related to metabolism at the early stage of storage,specifically those of the glycolysis and tricarboxylic acid cycle pathways.Genes related to the degradation of sucrose,starch,and cellulose were inhibited,and some starch and cellulose synthesis genes were up-regulated by 1-MCP.Apart from ethylene synthesis and signal transduction being inhibited by 1-MCP,several enzymes(pectinesterase,pectate lyase,polygalacturonase)were involved in pectin degradation,and degradation products of the cell wall(i.e.D-galacturonic acid and D-glucuronic acid)were also strongly inhibited,further maintaining fruit firmness.Cysteine,as precursor glutathione(GSH)related to plant resistance,up-regulated the synthase gene.However,the expression of genes related to cyanoalanine syn-thase and amino acid utilization pathways was suppressed by 1-MCP Collectively,1-MCP could maintain the postharvest quality of apple fruits.

关键词： 1-Methylcyclopropene apple fruit quality metabolomics transcriptomics

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Rodent models and metabolomics in non-alcoholic fatty liver disease: What can we learn?

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World Journal of Hepatology 2022年第2期14卷 304-318页

作者： Maria Martin-Grau Vannina G Marrachelli Daniel Monleon Department of Pathology University of ValenciaValencia 46010Spain Department of Physiology University of ValenciaValencia 46010Spain Health Research Institute INCLIVA Valencia 46010Spain CIBER de Fragilidad y Envejecimiento Saludable(CIBERfes) Madrid 28029Spain

Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis,which can progress to fibrosis.Several molecular and metabolic changes are required for the hepatocyte to finally vary its function;hence a“multiple hit”hypothesis seems a more accurate proposal.Previous studies and current knowledge suggest that in most cases,NAFLD initiates and progresses through most of nine hallmarks of the disease,although the triggers and mechanisms for these can vary widely.The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge.Among certain requirements to be met,a good model must imitate certain aspects of the human NAFLD disorder,be reliable and reproducible,have low mortality,and be compatible with a simple and feasible method.Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease.metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding.In this review,we provide a brief introduction to NAFLD hallmarks,the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.

关键词： Non-alcoholic fatty liver disease Liver disease Rodent models Metabolic profiling metabolomics Biomarkers

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Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach

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Chinese Herbal Medicines 2023年第3期15卷 430-438页

作者： Jing Sun Xianyang Chen Yongru Wang Yuelin Song Bo Pan Bei Fan Fengzhong Wang Xiaonan Chen Pengfei Tu Jiarui Han Huixia Huo Jun Li Modern Research Center for Traditional Chinese Medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process Laboratory of Agro-products Quality Safety Risk AssessmentMinistry of AgricultureInstitute of Food Science and TechnologyChinese Academy of Agricultural SciencesBeijing 100193China Baofeng Key Laboratory of Genetics and Metabolism Zhongguancun Biological and Medical Big Data CenterBeijing 101300China

Objective:The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule(LTC)on ischemic stroke rats.Methods:Twenty-six rats were randomly divided into four groups,including sham group,sham+LTC group,MCAO group,and MCAO+LTC group.Ischemic stroke rats were simulated by middle cerebral artery occlusion(MCAO),and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days.LTC therapy was validated in terms of neurobehavioral abnormality evaluation,cerebral infarct area,and histological assessments.The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis,aiming to finding the molecules in respond to the surgery or LTC treatment.Results:Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats.The interstitial edema,atrophy,and pyknosis of glial and neuronal cells occurred in the infarcted area,core area,and marginal area of cerebral cortex were improved after LTC treatment.A total of 13 potential biomarkers were observed,and Youden index of 11 biomarkers such as LysoPC,SM,and PE were more than 0.7,which were involved in neuroprotective process.The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism,together with nicotinate and nicotinamide metabolism.Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC.Conclusion:The present study could provide evidence that metabolomics,as systematic approach,revealed its capacity to evaluate the holistic efficacy of TCM,and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

关键词： ischemic stroke Longxue Tongluo Capsule metabolomics middle cerebral artery occlusion phenolic compounds UHPLC-Q Exactive MS

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Integration of metabolomics and transcriptomics revealed the biosynthetic mechanism of anti-parasitic compounds in Salinivibrio proteolyticus strain YCSC6

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Journal of Oceanology and Limnology 2022年第1期40卷 245-259页

作者： Guangxun DU Lingyun QU Ping GAO Wenhao HUANG Chenghua LI Dewen DING School of Marine Sciences Ningbo UniversityNingbo 315832China Laboratory for Marine Fisheries Science and Food Production Processes Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China Key Laboratory of Marine Eco-Environmental Science and Technology First Institute of OceanographyMinistry of Natural Resources(MNR)Qingdao 266061China

The fermentation broth of Salinivibrio proteolyticus strain YCSC6 shows potent anti-parasitic activity against Uronema marinum,with activity varying in each fermentation stage.To investigate the biosynthetic mechanism of anti-parasitic compounds in strain YCSC6,a comprehensive analysis of metabolomics and transcriptomics over four diff erent time points(12,24,48,and 72 h)was performed.metabolomics detected 17943 metabolites with 1129 known metabolites.A trend analysis of the known metabolites showed that 575 metabolites,including 69 polyketides,were continuously enhanced,being the potential source of anti-parasitic agents.In addition,941 genes mapped to the same pathways of these metabolites,were screened through the association analysis of metabolites and genes.KEGG pathway enrichment of these genes showed 270 genes mapped to the biosynthesis of secondary metabolites and 192 genes mapped to the biosynthesis of antibiotics.This demonstrates the potent secondary metabolic capacity of strain YCSC6.Finally,a gene-metabolite correlation network was created based on the 575 continuously enhanced metabolites and 43 continuously up-regulated genes.This revealed 13 genes at the key position that mapped to a putative metabolic pathway associated with the biosynthesis of polyketides and caprylic acid,which contributes to the potent anti-parasitic activity of strain YCSC6.This comprehensive analysis of metabolomics and transcriptomics provides insights into the biosynthetic mechanisms of anti-parasitic compounds in strain YCSC6 and guides the exploitation of more anti-parasitic agents for aquaculture.

关键词： metabolomics transcriptomics anti-parasitic Salinivibrio proteolyticus Uronema marinum

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