1
|
Saeed A, McKennan C, Duan J, Yang YN, Kip KE, Finegold D, Vu M, Swanson J, Lopez OL, Cohen A, Mapstone M, Yu B, Ballantyne CM, Reis SE. Mid-life anti-inflammatory metabolites are inversely associated with long-term cardiovascular disease events. EBioMedicine 2025; 112:105551. [PMID: 39793479 PMCID: PMC11764641 DOI: 10.1016/j.ebiom.2024.105551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 12/23/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known. METHODS We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.1 ± 7.5 years old, 69.6% female, 43.6% self-identified as Black) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Logistic regression was used to assess the impact of metabolite levels on ASCVD risk (nonfatal MI, revascularisation, and cardiac mortality). We additionally explored the effect of genetic variants neighbouring ASCVD-related genes on the levels of metabolites predictive of ASCVD events. The Atherosclerosis Risk in Communities (ARIC) study (n = 4790; 75.5 ± 5.1 years old, 57.4% female, 19.5% self-identified as Black) was used as an independent validation cohort. FINDINGS In fully adjusted models, alpha-ketobutyrate [AKB] (OR 0.62 [95% CI, 0.49-0.80]; p < 0.001), and 1-palmitoyl-2-linoleoyl-GPI [OR, 0.62, 95% CI, 0.47-0.83; p < 0.001], two metabolites in amino acid and phosphatidylinositol lipid pathways, respectively, showed a significant protective association with incident ASCVD risk in both Heart SCORE and ARIC cohorts. Three plasmalogens and a bilirubin derivative, whose levels were regulated by genetic variants neighbouring FADS1 and UGT1A1, respectively, exhibited a significant protective association with ASCVD risk in the Heart SCORE only. INTERPRETATION Higher mid-life levels of AKB and 1-palmitoyl-2-linoleoyl-GPI metabolites may be associated with lower risk late-life ASCVD events. Further research can determine the causality and therapeutic potential of these metabolites in ASCVD. FUNDING This study was funded by the Pennsylvania Department of Health (ME-02-384). The department specifically disclaims responsibility for any analyses, interpretations, or conclusions. Additional funding was provided by National Institutes of Health (NIH) grant R01HL089292 and UL1 TR001857 (Steven Reis). Further, NIH funded R01HL141824 and R01HL168683 were used for the ARIC study validation (Bing Yu).
Collapse
Affiliation(s)
- Anum Saeed
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Heart and Vascular Institute, UPMC, Pittsburgh, PA, USA.
| | - Chris McKennan
- Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jiaxuan Duan
- Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Kevin E Kip
- Clinical Analytics, UPMC Health Services Division, Pittsburgh, PA, USA
| | - David Finegold
- University of Pittsburgh School of Public Health, Pittsburgh, PA, USA
| | - Michael Vu
- Department of Neurology, University of California, Irvine, Irvine, CA, USA
| | | | - Oscar L Lopez
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Cognitive and Behavioral and Neurology Division, UPMC, Pittsburgh, PA, USA
| | - Ann Cohen
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Mark Mapstone
- Department of Neurology, University of California, Irvine, Irvine, CA, USA
| | - Bing Yu
- University of Texas Health Sciences, Houston, TX, USA
| | | | - Steven E Reis
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Heart and Vascular Institute, UPMC, Pittsburgh, PA, USA
| |
Collapse
|
2
|
Demicheva E, Polanco Espino FJ, Vedeneev P, Shevyrin V, Buhler A, Mukhlynina E, Berdiugina O, Mondragon ADC, Cepeda Sáez A, Lopez-Santamarina A, Cardelle-Cobas A, Solovyova O, Danilova I, Miranda JM, Kovaleva E. Comparative Study of Lipid Profile for Mice Treated with Cyclophosphamide by HPLC-HRMS and Bioinformatics. Metabolites 2025; 15:60. [PMID: 39852402 PMCID: PMC11767742 DOI: 10.3390/metabo15010060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 01/26/2025] Open
Abstract
Purpose: Immunodeficiency conditions, which are characterized by reduced immune activity that promotes the development of chronic diseases, are needed for efficient monitoring. A promising area of monitoring and early diagnosis of immunodeficiency diseases is the determination of metabolic biomarkers in the blood. Methods: In this work, we identified a set of lipid biomarkers of immunodeficiency states by performing high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) analysis of blood plasma samples from mice and processing them with bioinformatics approaches. Potential biomarkers were selected through statistical analysis and further validated by MS/MS. Conclusions: As a result, 15 lipids were confirmed and selected as potential biomarkers of immunodeficiency states. The selected biomarkers can be further studied and serve as promising targets for the early diagnosis of immunodeficiency diseases.
Collapse
Affiliation(s)
- Ekaterina Demicheva
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (F.J.P.E.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia;
| | - Fernando Jonathan Polanco Espino
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (F.J.P.E.); (A.B.); (E.M.); (O.S.); (I.D.)
| | - Pavel Vedeneev
- Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620002, Russia; (P.V.); (V.S.); (E.K.)
| | - Vadim Shevyrin
- Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620002, Russia; (P.V.); (V.S.); (E.K.)
| | - Aleksey Buhler
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (F.J.P.E.); (A.B.); (E.M.); (O.S.); (I.D.)
| | - Elena Mukhlynina
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (F.J.P.E.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia;
| | - Olga Berdiugina
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia;
| | - Alicia del Carmen Mondragon
- Laboratorio de Higiene, Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain; (A.d.C.M.); (A.C.S.); (A.L.-S.); (A.C.-C.); (J.M.M.)
| | - Alberto Cepeda Sáez
- Laboratorio de Higiene, Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain; (A.d.C.M.); (A.C.S.); (A.L.-S.); (A.C.-C.); (J.M.M.)
| | - Aroa Lopez-Santamarina
- Laboratorio de Higiene, Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain; (A.d.C.M.); (A.C.S.); (A.L.-S.); (A.C.-C.); (J.M.M.)
| | - Alejandra Cardelle-Cobas
- Laboratorio de Higiene, Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain; (A.d.C.M.); (A.C.S.); (A.L.-S.); (A.C.-C.); (J.M.M.)
| | - Olga Solovyova
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (F.J.P.E.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia;
| | - Irina Danilova
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (F.J.P.E.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia;
| | - Jose Manuel Miranda
- Laboratorio de Higiene, Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain; (A.d.C.M.); (A.C.S.); (A.L.-S.); (A.C.-C.); (J.M.M.)
| | - Elena Kovaleva
- Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620002, Russia; (P.V.); (V.S.); (E.K.)
| |
Collapse
|
3
|
Aldridge CM, Keene KL, Normeshie CA, Mychaleckyj JC, Hauck FR. Metabolomic profiles of infants classified as sudden infant death syndrome: a case-control analysis. EBioMedicine 2025; 111:105484. [PMID: 39644771 PMCID: PMC11667177 DOI: 10.1016/j.ebiom.2024.105484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 12/09/2024] Open
Abstract
BACKGROUND Sudden Infant Death Syndrome (SIDS) is a leading cause of postneonatal mortality. The absence of specific biomarkers of SIDS diagnosis and risk leaves a significant gap in understanding SIDS pathophysiology. Metabolomics offers an avenue to better understand SIDS biology and identifying potential biomarkers. METHODS Using Metabolon Inc., global discovery panel, we analysed 828 metabolites from post-mortem serum samples of infants from the Chicago Infant Mortality Study (CIMS) and the NIH NeuroBioBank (NBB). In total, 300 infants (195 SIDS; 105 non-SIDS) across multiple race/ethnicities (70% Black, 13% White, and 16% Hispanic) were included. Metabolite associations with SIDS were performed using Welch's t-tests, linear and logistic regression, and network-cluster analyses. FINDINGS We identified thirty-five significant metabolite predictors of SIDS after adjustment for age, sex, race and ethnicity, and post-mortem interval, including ornithine (OR 21.98; p-value 6.44e-7), 5-hydroxylysine (OR 19.48; p-value 6.78e-7), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2) (OR 16.80; p-value 3.4e-7), ribitol (OR 8.19; p-value 4.2e-8), and arabitol/xylitol. Using Weighted Gene Co-expression Network Analysis (WGCNA), ten metabolite clusters were identified. Four exhibited significant associations with SIDS. The two most correlated clusters were enriched for metabolites in the tyrosine metabolism pathway and lipid (sphingomyelins) pathways. INTERPRETATION We identified metabolite biomarkers within key biological pathways and processes (e.g., nitrogen metabolism, lipid and fatty acid metabolism, stress response, nerve cell communication, hormone regulation, oxidative stress) with potential implications in SIDS pathology. Further research is needed to validate these biomarkers in additional SIDS cohorts. FUNDING The Chicago Infant Mortality Study was funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Deafness and Other Communication Disorders under contract number NO1-HD-3-3188, the Centers for Disease Control and Prevention and the Association of Teachers of Preventive Medicine under cooperative agreement number U50/CCU300860-06, and the Playmates in Heaven Foundation. The current analyses were funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development under 5R01HD101518-04.
Collapse
Affiliation(s)
- Chad M Aldridge
- Department of Neurology, University of Virginia, School of Medicine, Charlottesville, VA, USA
| | - Keith L Keene
- Department of Public Health Sciences, University of Virginia, School of Medicine, Charlottesville, VA, USA; Department of Genome Sciences, University of Virginia, School of Medicine, Charlottesville, VA, USA; Center for Health Equity and Precision Public Health, University of Virginia, School of Medicine, Charlottesville, VA, USA; Department of Biology, Center for Health Disparities, East Carolina University, Greenville, NC, USA.
| | - Cornelius A Normeshie
- Department of Family Medicine, University of Virginia, School of Medicine, Charlottesville, VA, USA
| | - Josyf C Mychaleckyj
- Department of Genome Sciences, University of Virginia, School of Medicine, Charlottesville, VA, USA
| | - Fern R Hauck
- Department of Public Health Sciences, University of Virginia, School of Medicine, Charlottesville, VA, USA; Department of Family Medicine, University of Virginia, School of Medicine, Charlottesville, VA, USA
| |
Collapse
|
4
|
Weng X, Gonzalez M, Angelia J, Piroozmand S, Jamehdor S, Behrooz AB, Latifi-Navid H, Ahmadi M, Pecic S. Lipidomics-driven drug discovery and delivery strategies in glioblastoma. Biochim Biophys Acta Mol Basis Dis 2024; 1871:167637. [PMID: 39722408 DOI: 10.1016/j.bbadis.2024.167637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 12/14/2024] [Accepted: 12/17/2024] [Indexed: 12/28/2024]
Abstract
With few viable treatment options, glioblastoma (GBM) is still one of the most aggressive and deadly types of brain cancer. Recent developments in lipidomics have demonstrated the potential of lipid metabolism as a therapeutic target in GBM. The thorough examination of lipids in biological systems, or lipidomics, is essential to comprehending the changed lipid profiles found in GBM, which are linked to the tumor's ability to grow, survive, and resist treatment. The use of lipidomics in drug delivery and discovery is examined in this study, focusing on how it may be used to find new biomarkers, create multi-target directed ligands, and improve drug delivery systems. We also cover the use of FDA-approved medications, clinical trials that use lipid-targeted medicines, and the integration of lipidomics with other omics technologies. This study emphasizes lipidomics as a possible tool in developing more effective treatment methods for GBM by exploring various lipid-centric techniques.
Collapse
Affiliation(s)
- Xiaohui Weng
- Department of Chemistry and Biochemistry, California State University Fullerton, Fullerton, CA 92831, United States
| | - Michael Gonzalez
- Department of Chemistry and Biochemistry, California State University Fullerton, Fullerton, CA 92831, United States
| | - Jeannes Angelia
- Department of Chemistry and Biochemistry, California State University Fullerton, Fullerton, CA 92831, United States
| | - Somayeh Piroozmand
- Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Saleh Jamehdor
- Department of Virology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir Barzegar Behrooz
- Department of Human Anatomy and Cell Sciences, University of Manitoba, Max Rady College of Medicine, Winnipeg, Manitoba, Canada
| | - Hamid Latifi-Navid
- Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.; Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Iran
| | - Mazaher Ahmadi
- Department of Analytical Chemistry, Faculty of Chemistry and Petroleum Sciences, Bu-Ali Sina University, Hamedan, Iran
| | - Stevan Pecic
- Department of Chemistry and Biochemistry, California State University Fullerton, Fullerton, CA 92831, United States.
| |
Collapse
|
5
|
Qin Y, Zhuang H, Zhang Y, Chen Y. Analysis of lipid composition of cell-bound membrane vesicles (CBMVs) derived from endothelial cells. Biochem Biophys Res Commun 2024; 733:150722. [PMID: 39332153 DOI: 10.1016/j.bbrc.2024.150722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 09/29/2024]
Abstract
Cell-bound membrane vesicles (CBMVs), a novel type of membrane vesicles, have been identified through a series of characterization tools. However, the lipid composition of CBMVs has not yet been characterized. This study focuses on the differences in lipid composition between CBMVs and cell membranes. In order to determine the lipid composition of CBMVs and cell membranes of Human umbilical vein endothelial cells (HUVECs) and find out differential metabolites, this study was carried out by isolating CBMVs lipids and characterizing them using high-performance liquid chromatography tandem secondary mass spectrometry (LC-MS/MS). The results showed the presence of 213 up-regulated and 726 down-regulated lipids in CBMVs compared to cell membranes which produced CBMVs. There are lipids expressed in CBMVs and not in cell membranes: DGDG 18:0_8:0, DGDG O-8:0_16:1, DGDG O-26:7_26:7, DGDG O-16:3_26:7, TG 15:4_21:5_22:5; 4O, PC 49:11, PG 19:5_38:10, PI 60:14, PI 44:9, PI 25:2, PI 43:5, PI 50:10, PS 55:10. DGDG (digalactosyl diglyceride), MGDG (monogalactosyl diglyceride) belongs to galactosyl diglyceride, promotes fat catabolism, which also has antioxidant and anti-inflammatory effects, and unsaturated diacylglycerols are a class of antioxidant compounds, which enables CBMVs to have a therapeutic potential.
Collapse
Affiliation(s)
- Ying Qin
- Jiangxi Key Laboratory for Microscale Interdisciplinary Study, Institute for Advanced Study, College of Pharmacy, Nanchang University, Nanchang, Jiangxi, 330031, PR China
| | - Hongda Zhuang
- Jiangxi Key Laboratory for Microscale Interdisciplinary Study, Institute for Advanced Study, College of Pharmacy, Nanchang University, Nanchang, Jiangxi, 330031, PR China
| | - Yuan Zhang
- Jiangxi Key Laboratory for Microscale Interdisciplinary Study, Institute for Advanced Study, College of Pharmacy, Nanchang University, Nanchang, Jiangxi, 330031, PR China
| | - Yong Chen
- Jiangxi Key Laboratory for Microscale Interdisciplinary Study, Institute for Advanced Study, College of Pharmacy, Nanchang University, Nanchang, Jiangxi, 330031, PR China.
| |
Collapse
|
6
|
Nguyen BT, Le QV, Ahn J, Nguyen KA, Nguyen HT, Kang JS, Long NP, Kim HM. Omics analysis unveils changes in the metabolome and lipidome of Caenorhabditis elegans upon polydopamine exposure. J Pharm Biomed Anal 2024; 244:116126. [PMID: 38581931 DOI: 10.1016/j.jpba.2024.116126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/14/2024] [Accepted: 03/26/2024] [Indexed: 04/08/2024]
Abstract
Polydopamine (PDA) is an insoluble biopolymer with a dark brown-black color that forms through the autoxidation of dopamine. Because of its outstanding biocompatibility and durability, PDA holds enormous promise for various applications, both in the biomedical and non-medical domains. To ensure human safety, protect health, and minimize environmental impacts, the assessment of PDA toxicity is important. In this study, metabolomics and lipidomics assessed the impact of acute PDA exposure on Caenorhabditis elegans (C. elegans). The findings revealed a pronounced perturbation in the metabolome and lipidome of C. elegans at the L4 stage following 24 hours of exposure to 100 µg/mL PDA. The changes in lipid composition varied based on lipid classes. Increased lipid classes included lysophosphatidylethanolamine, triacylglycerides, and fatty acids, while decreased species involved in several sub-classes of glycerophospholipids and sphingolipids. Besides, we detected 37 significantly affected metabolites in the positive and 8 in the negative ion modes due to exposure to PDA in C. elegans. The metabolites most impacted by PDA exposure were associated with purine metabolism, biosynthesis of valine, leucine, and isoleucine; aminoacyl-tRNA biosynthesis; and cysteine and methionine metabolism, along with pantothenate and CoA biosynthesis; the citrate cycle (TCA cycle); and beta-alanine metabolism. In conclusion, PDA exposure may intricately influence the metabolome and lipidome of C. elegans. The combined application of metabolomics and lipidomics offers additional insights into the metabolic perturbations involved in PDA-induced biological effects and presents potential biomarkers for the assessment of PDA safety.
Collapse
Affiliation(s)
- Bao Tan Nguyen
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Quoc-Viet Le
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam
| | - Jeongjun Ahn
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Ky Anh Nguyen
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam
| | - Huy Truong Nguyen
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam
| | - Jong Seong Kang
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Nguyen Phuoc Long
- Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan 47392, Republic of Korea.
| | - Hyung Min Kim
- College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
| |
Collapse
|
7
|
Zuo Q, Wu Y, Hu Y, Shao C, Liang Y, Chen L, Guo Q, Huang P, Chen Q. Targeting lipid reprogramming in the tumor microenvironment by traditional Chinese medicines as a potential cancer treatment. Heliyon 2024; 10:e30807. [PMID: 38765144 PMCID: PMC11101863 DOI: 10.1016/j.heliyon.2024.e30807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 05/06/2024] [Accepted: 05/06/2024] [Indexed: 05/21/2024] Open
Abstract
In the last ten years, there has been a notable rise in the study of metabolic abnormalities in cancer cells. However, compared to glucose or glutamine metabolism, less attention has been paid to the importance of lipid metabolism in tumorigenesis. Recent developments in lipidomics technologies have allowed for detailed analysis of lipid profiles within cancer cells and other cellular players present within the tumor microenvironment (TME). Traditional Chinese medicine (TCM) and its bioactive components have a long history of use in cancer treatments and are also being studied for their potential role in regulating metabolic reprogramming within TME. This review focuses on four core abnormalities altered by lipid reprogramming in cancer cells: de novo synthesis and exogenous uptake of fatty acids (FAs), upregulated fatty acid oxidation (FAO), cholesterol accumulation, which offer benefits for tumor growth and metastasis. The review also discusses how altered lipid metabolism impacts infiltrating immune cell function and phenotype as these interactions between cancer-stromal become more pronounced during tumor progression. Finally, recent literature is highlighted regarding how cancer cells can be metabolically reprogrammed by specific Chinese herbal components with potential therapeutic benefits related to lipid metabolic and signaling pathways.
Collapse
Affiliation(s)
- Qian Zuo
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Yingchao Wu
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuyu Hu
- Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Guangdong Academy of Traditional Chinese Medicine, Guangzhou, China
| | - Cui Shao
- The First Affiliated Traditional Chinese Medicine Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yuqi Liang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liushan Chen
- Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Guangdong Academy of Traditional Chinese Medicine, Guangzhou, China
| | - Qianqian Guo
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Ping Huang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Qianjun Chen
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- Guangdong Academy of Traditional Chinese Medicine, Guangzhou, China
| |
Collapse
|
8
|
Aly AA, Górecki T. Two-dimensional liquid chromatography with reversed phase in both dimensions: A review. J Chromatogr A 2024; 1721:464824. [PMID: 38522405 DOI: 10.1016/j.chroma.2024.464824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/14/2024] [Accepted: 03/16/2024] [Indexed: 03/26/2024]
Abstract
Two-dimensional liquid chromatography (2D-LC), and in particular comprehensive two-dimensional liquid chromatography (LC×LC), offers increased peak capacity, resolution and selectivity compared to one-dimensional liquid chromatography. It is commonly accepted that the technique produces the best results when the separation mechanisms in the two dimensions are completely orthogonal; however, the use of similar separation mechanisms in both dimensions has been gaining popularity as it helps avoid difficulties related to mobile phase incompatibility and poor column efficiency. The remarkable advantages of using reversed phase in both dimensions (RPLC×RPLC) over other separation mechanisms made it a promising technique in the separation of complex samples. This review discusses some physical and practical considerations in method development for 2D-LC involving the use of RP in both dimensions. In addition, an extensive overview is presented of different applications that relied on RPLC×RPLC and 2D-LC with reversed phase column combinations to separate components of complex samples in different fields including food analysis, natural product analysis, environmental analysis, proteomics, lipidomics and metabolomics.
Collapse
Affiliation(s)
- Alshymaa A Aly
- Analytical Chemistry Department, Faculty of Pharmacy, Minia University, Menia Governorate, Arab Republic of Egypt; Department of Chemistry, University of Waterloo, ON, Canada
| | - Tadeusz Górecki
- Department of Chemistry, University of Waterloo, ON, Canada.
| |
Collapse
|
9
|
Bernardo RA, Roque JV, de Oliveira Júnior CI, Lima NM, Machado LS, Duarte GRM, Costa NL, Sorgi CA, Soares FFL, Vaz BG, Chaves AR. Exploring salivary lipid profile changes in COVID-19 patients: Insights from mass spectrometry analysis. Talanta 2024; 269:125522. [PMID: 38091738 DOI: 10.1016/j.talanta.2023.125522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/27/2023] [Accepted: 12/04/2023] [Indexed: 01/05/2024]
Abstract
The most common COVID-19 testing relies on the use of nasopharyngeal swabs. However, this sampling step is very uncomfortable and is one of the biggest challenges regarding population testing. In the present study, the use of saliva as an alternative sample for COVID-19 diagnosis was investigated. Therefore, high-resolution mass spectrometry analysis and chemometric approaches were applied to salivary lipid extracts. Two data organizations were used: classical MS data and pseudo-MS image datasets. The latter transformed MS data into pseudo-images, simplifying data interpretation. Classification models achieved high accuracy, with pseudo-MS image data performing exceptionally well. PLS-DA with OPSDA successfully separated COVID-19 and healthy groups, serving as a potential diagnostic tool. The most important lipids for COVID-19 classification were elucidated and include sphingolipids, ceramides, phospholipids, and glycerolipids. These lipids play a crucial role in viral replication and the inflammatory response. While pseudo-MS image data excelled in classification, it lacked the ability to annotate important variables, which was performed using classical MS data. These findings have the potential to improve clinical diagnosis using rapid, non-invasive testing methods and accurate high-volume results.
Collapse
Affiliation(s)
- Ricardo A Bernardo
- Instituto de Química, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil; Departamento de Química, Universidade Federal do Paraná, 81531-980, Curitiba, PR, Brazil.
| | - Jussara V Roque
- Instituto de Química, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil
| | - Charles I de Oliveira Júnior
- Instituto de Química, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil; Departamento de Química, Universidade Federal de Jataí, 75804-020, Jataí, GO, Brazil
| | | | - Lucas Santos Machado
- Instituto de Química, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil
| | | | - Nádia L Costa
- Faculdade de Odontologia, Universidade Federal de Goiás, 74605-020, Goiânia, GO, Brazil
| | - Carlos A Sorgi
- Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14015-130, Ribeirão Preto, SP, Brazil
| | - Frederico F L Soares
- Departamento de Química, Universidade Federal do Paraná, 81531-980, Curitiba, PR, Brazil
| | - Boniek G Vaz
- Instituto de Química, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil
| | - Andréa R Chaves
- Instituto de Química, Universidade Federal de Goiás, 74690-900, Goiânia, GO, Brazil; Departamento de Química, Universidade Federal de Jataí, 75804-020, Jataí, GO, Brazil.
| |
Collapse
|
10
|
Waly DA, Zeid AHA, Attia HN, Ahmed KA, El-Kashoury ESA, El Halawany AM, Mohammed RS. Comprehensive phytochemical characterization of Persea americana Mill. fruit via UPLC/HR-ESI-MS/MS and anti-arthritic evaluation using adjuvant-induced arthritis model. Inflammopharmacology 2023; 31:3243-3262. [PMID: 37936023 PMCID: PMC10692038 DOI: 10.1007/s10787-023-01365-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/06/2023] [Indexed: 11/09/2023]
Abstract
Persea americana Mill. (avocado fruit) has many health benefits when added to our diet due to various pharmacological activities, such as preventing bone loss and inflammation, modulating immune response and acting as an antioxidant. In the current study, the total ethanol extract (TEE) of the fruit was investigated for in vitro antioxidant and anti-inflammatory activity via DPPH and cyclooxygenase enzyme inhibition. Biological evaluation of the antiarthritic effect of the fruit extract was further investigated in vivo using Complete Freund's Adjuvant (CFA) arthritis model, where the average percentages of body weight change, inhibition of paw edema, basal paw diameter/weight and spleen index were estimated for all animal groups. Inflammatory mediators such as serum IL-6 and TNF-α were also determined, in addition to histopathological examination of the dissected limbs isolated from all experimental animals. Eighty-one metabolites belonging to different chemical classes were detected in the TEE of P. americana fruit via UPLC/HR-ESI-MS/MS. Two classes of lyso-glycerophospholipids; lyso-glycerophosphoethanolamines and lysoglycerophosphocholines were detected for the first time in avocado fruit in the positive mode. The TEE of fruit exhibited significant antioxidant and anti-inflammatory activity in vitro. In vivo anti-arthritic activity of the fruit TEE improved paw parameters, inflammatory mediators and spleen index. Histopathological findings showed marked improvements in the arthritic condition of the excised limbs. Therefore, avocado fruit could be proposed to be a powerful antioxidant and antiarthritic natural product.
Collapse
Affiliation(s)
- Dina Atef Waly
- Department of Pharmacognosy, National Research Centre (ID: 60014618), 33-Elbohouth St (Former El-Tahrir St.), Dokki, P.O. 12622, Giza, Egypt.
| | - Aisha Hussein Abou Zeid
- Department of Pharmacognosy, National Research Centre (ID: 60014618), 33-Elbohouth St (Former El-Tahrir St.), Dokki, P.O. 12622, Giza, Egypt
| | - Hanan Naeim Attia
- Medicinal and Pharmaceutical Chemistry Department (Pharmacology Group), National Research Centre (ID: 60014618), 33-Elbohouth St (Former El-Tahrir St.), Dokki, P.O. 12622, Giza, Egypt
| | - Kawkab A Ahmed
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, P.O. 12211, Giza, Egypt
| | | | - Ali Mahmoud El Halawany
- Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr-El Ainy Street, Cairo, 11562, Egypt
| | - Reda Sayed Mohammed
- Department of Pharmacognosy, National Research Centre (ID: 60014618), 33-Elbohouth St (Former El-Tahrir St.), Dokki, P.O. 12622, Giza, Egypt.
| |
Collapse
|
11
|
Hormann FL, Sommer S, Heiles S. Formation and Tandem Mass Spectrometry of Doubly Charged Lipid-Metal Ion Complexes. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2023. [PMID: 37315187 DOI: 10.1021/jasms.3c00126] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Phospholipids are major components of most eukaryotic cell membranes. Changes in metabolic states are often accompanied by phospholipid structure variations. The structural changes of phospholipids are the hallmark of disease states, or specific lipid structures have been associated with distinct organisms. Prime examples are microorganisms that synthesize phospholipids with, for example, different branched chain fatty acids. Assignment and relative quantitation of structural isomers of phospholipids that arise from attachment of different fatty acids to the glycerophospholipid backbone are difficult with routine tandem mass spectrometry or with liquid chromatography without authentic standards. In this work, we report on the observation that all investigated phospholipid classes form doubly charged lipid-metal ion complexes during electrospray ionization (ESI) and show that these complexes can be used to assign lipid classes and fatty acid moieties, distinguish isomers of branched chain fatty acids, and relatively quantify these isomers in positive-ion mode. Use of water free methanol and addition of divalent metal salts (100 mol %) to ESI spray solutions afford highly abundant doubly charged lipid-metal ion complexes (up to 70 times of protonated compounds). Higher-energy collisional dissociation and collision-induced dissociation of doubly charged complexes yield a diverse set of lipid class-dependent fragment ions. In common for all lipid classes is the liberation of fatty acid-metal adducts that yield fragment ions from the fatty acid hydrocarbon chain upon activation. This ability is used to pinpoint sites of branching in saturated fatty acids and is showcased for free fatty acids as well as glycerophospholipids. The analytical utility of doubly charged phospholipid-metal ion complexes is demonstrated by distinguishing fatty acid branching-site isomers in phospholipid mixtures and relatively quantifying the corresponding isomeric compounds.
Collapse
Affiliation(s)
- Felix-Levin Hormann
- Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Otto-Hahn-Straße 6b, 44139 Dortmund, Germany
- Lipidomics, Faculty of Chemistry, University of Duisburg-Essen, Universitätsstrasse 5, 45141 Essen, Germany
| | - Simon Sommer
- Institute of Inorganic and Analytical Chemistry, Justus Liebig University Giessen, 35392 Giessen, Germany
| | - Sven Heiles
- Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Otto-Hahn-Straße 6b, 44139 Dortmund, Germany
- Lipidomics, Faculty of Chemistry, University of Duisburg-Essen, Universitätsstrasse 5, 45141 Essen, Germany
| |
Collapse
|
12
|
Ren W, Sun M, Shi X, Wang T, Wang Y, Wang C, Li M. Progress of Mass Spectrometry-Based Lipidomics in the Dairy Field. Foods 2023; 12:foods12112098. [PMID: 37297344 DOI: 10.3390/foods12112098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/11/2023] [Accepted: 05/20/2023] [Indexed: 06/12/2023] Open
Abstract
Lipids play important biological roles, such as providing essential fatty acids and signaling. The wide variety and structural diversity of lipids, and the limited technical means to study them, have seriously hampered the resolution of the mechanisms of action of lipids. With advances in mass spectrometry (MS) and bioinformatic technologies, large amounts of lipids have been detected and analyzed quickly using MS-based lipidomic techniques. Milk lipids, as complex structural metabolites, play a crucial role in human health. In this review, the lipidomic techniques and their applications to dairy products, including compositional analysis, quality identification, authenticity identification, and origin identification, are discussed, with the aim of providing technical support for the development of dairy products.
Collapse
Affiliation(s)
- Wei Ren
- School of Agricultural Science and Engineering, Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 252000, China
| | - Mengqi Sun
- School of Agricultural Science and Engineering, Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 252000, China
| | - Xiaoyuan Shi
- School of Agricultural Science and Engineering, Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 252000, China
| | - Tianqi Wang
- School of Agricultural Science and Engineering, Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 252000, China
| | - Yonghui Wang
- School of Agricultural Science and Engineering, Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 252000, China
| | - Changfa Wang
- School of Agricultural Science and Engineering, Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 252000, China
| | - Mengmeng Li
- School of Agricultural Science and Engineering, Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 252000, China
| |
Collapse
|
13
|
Dadashkhan S, Mirmotalebisohi SA, Poursheykhi H, Sameni M, Ghani S, Abbasi M, Kalantari S, Zali H. Deciphering crucial genes in multiple sclerosis pathogenesis and drug repurposing: A systems biology approach. J Proteomics 2023; 280:104890. [PMID: 36966969 DOI: 10.1016/j.jprot.2023.104890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 02/14/2023] [Accepted: 03/09/2023] [Indexed: 04/10/2023]
Abstract
This study employed systems biology and high-throughput technologies to analyze complex molecular components of MS pathophysiology, combining data from multiple omics sources to identify potential biomarkers and propose therapeutic targets and repurposed drugs for MS treatment. This study analyzed GEO microarray datasets and MS proteomics data using geWorkbench, CTD, and COREMINE to identify differentially expressed genes associated with MS disease. Protein-protein interaction networks were constructed using Cytoscape and its plugins, and functional enrichment analysis was performed to identify crucial molecules. A drug-gene interaction network was also created using DGIdb to propose medications. This study identified 592 differentially expressed genes (DEGs) associated with MS disease using GEO, proteomics, and text-mining datasets. 37 DEGs were found to be important by topographical network studies, and 6 were identified as the most significant for MS pathophysiology. Additionally, we proposed six drugs that target these key genes. Crucial molecules identified in this study were dysregulated in MS and likely play a key role in the disease mechanism, warranting further research. Additionally, we proposed repurposing certain FDA-approved drugs for MS treatment. Our in silico results were supported by previous experimental research on some of the target genes and drugs. SIGNIFICANCE: As the long-lasting investigations continue to discover new pathological territories in neurodegeneration, here we apply a systems biology approach to determine multiple sclerosis's molecular and pathophysiological origin and identify multiple sclerosis crucial genes that contribute to candidating new biomarkers and proposing new medications.
Collapse
Affiliation(s)
- Sadaf Dadashkhan
- Molecular Medicine Research Centre, Universitätsklinikum Jena, Jena, Germany; Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Seyed Amir Mirmotalebisohi
- Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Poursheykhi
- Department of New Scientist, Faculty of Medical Sciences, Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Marzieh Sameni
- Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Ghani
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Sima Kalantari
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Regenerative Medicine Group (REMED), Universal Scientific Education & Research Network (USERN), Tehran, Iran
| | - Hakimeh Zali
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
14
|
Analysis of milk with liquid chromatography–mass spectrometry: a review. Eur Food Res Technol 2023. [DOI: 10.1007/s00217-022-04197-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
AbstractAs a widely consumed foodstuff, milk and dairy products are increasingly studied over the years. At the present time, milk profiling is used as a benchmark to assess the properties of milk. Modern biomolecular mass spectrometers have become invaluable to fully characterize the milk composition. This review reports the analysis of milk and its components using liquid chromatography coupled with mass spectrometry (LC–MS). LC–MS analysis as a whole will be discussed subdivided into the major constituents of milk, namely, lipids, proteins, sugars and the mineral fraction.
Collapse
|
15
|
Ni Z, Wölk M, Jukes G, Mendivelso Espinosa K, Ahrends R, Aimo L, Alvarez-Jarreta J, Andrews S, Andrews R, Bridge A, Clair GC, Conroy MJ, Fahy E, Gaud C, Goracci L, Hartler J, Hoffmann N, Kopczyinki D, Korf A, Lopez-Clavijo AF, Malik A, Ackerman JM, Molenaar MR, O'Donovan C, Pluskal T, Shevchenko A, Slenter D, Siuzdak G, Kutmon M, Tsugawa H, Willighagen EL, Xia J, O'Donnell VB, Fedorova M. Guiding the choice of informatics software and tools for lipidomics research applications. Nat Methods 2023; 20:193-204. [PMID: 36543939 PMCID: PMC10263382 DOI: 10.1038/s41592-022-01710-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 11/02/2022] [Indexed: 12/24/2022]
Abstract
Progress in mass spectrometry lipidomics has led to a rapid proliferation of studies across biology and biomedicine. These generate extremely large raw datasets requiring sophisticated solutions to support automated data processing. To address this, numerous software tools have been developed and tailored for specific tasks. However, for researchers, deciding which approach best suits their application relies on ad hoc testing, which is inefficient and time consuming. Here we first review the data processing pipeline, summarizing the scope of available tools. Next, to support researchers, LIPID MAPS provides an interactive online portal listing open-access tools with a graphical user interface. This guides users towards appropriate solutions within major areas in data processing, including (1) lipid-oriented databases, (2) mass spectrometry data repositories, (3) analysis of targeted lipidomics datasets, (4) lipid identification and (5) quantification from untargeted lipidomics datasets, (6) statistical analysis and visualization, and (7) data integration solutions. Detailed descriptions of functions and requirements are provided to guide customized data analysis workflows.
Collapse
Affiliation(s)
- Zhixu Ni
- Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany
| | - Michele Wölk
- Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany
| | - Geoff Jukes
- Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK
| | | | - Robert Ahrends
- Department of Analytical Chemistry, University of Vienna, Vienna, Austria
| | - Lucila Aimo
- Swiss-Prot group, SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, Geneva, Switzerland
| | - Jorge Alvarez-Jarreta
- Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK
- European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK
| | - Simon Andrews
- Babraham Institute, Babraham Research Campus, Cambridge, UK
| | - Robert Andrews
- Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK
| | - Alan Bridge
- Swiss-Prot group, SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, Geneva, Switzerland
| | - Geremy C Clair
- Biological Science Division, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Matthew J Conroy
- Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK
| | - Eoin Fahy
- Department of Bioengineering, University of California, San Diego, CA, USA
| | - Caroline Gaud
- Babraham Institute, Babraham Research Campus, Cambridge, UK
| | - Laura Goracci
- Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy
| | - Jürgen Hartler
- Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria
- Field of Excellence BioHealthe-University of Graz, Graz, Austria
| | - Nils Hoffmann
- Center for Biotechnology, University of Bielefeld, Bielefeld, Germany
| | - Dominik Kopczyinki
- Department of Analytical Chemistry, University of Vienna, Vienna, Austria
| | - Ansgar Korf
- Bruker Daltonics GmbH & Co. KG, Bremen, Germany
| | | | - Adnan Malik
- European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK
| | | | - Martijn R Molenaar
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Claire O'Donovan
- European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK
| | - Tomáš Pluskal
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic
| | - Andrej Shevchenko
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Denise Slenter
- Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, The Netherlands
| | - Gary Siuzdak
- Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA, USA
| | - Martina Kutmon
- Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, The Netherlands
- Maastricht Centre for Systems Biology, Maastricht University, Maastricht, The Netherlands
| | - Hiroshi Tsugawa
- Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo, Japan
- RIKEN Center for Sustainable Resource Science, Yokohama, Japan
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
- Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan
| | - Egon L Willighagen
- Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, The Netherlands
| | - Jianguo Xia
- Institute of Parasitology, McGill University, Montreal, Canada
| | - Valerie B O'Donnell
- Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK.
| | - Maria Fedorova
- Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany.
| |
Collapse
|
16
|
Alabed HBR, Gorello P, Pellegrino RM, Lancioni H, La Starza R, Taddei AA, Urbanelli L, Buratta S, Fernandez AGL, Matteucci C, Caniglia M, Arcioni F, Mecucci C, Emiliani C. Comparison between Sickle Cell Disease Patients and Healthy Donors: Untargeted Lipidomic Study of Erythrocytes. Int J Mol Sci 2023; 24:ijms24032529. [PMID: 36768849 PMCID: PMC9917006 DOI: 10.3390/ijms24032529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023] Open
Abstract
Sickle cell disease (SCD) is one of the most common severe monogenic disorders in the world caused by a mutation on HBB gene and characterized by hemoglobin polymerization, erythrocyte rigidity, vaso-occlusion, chronic anemia, hemolysis, and vasculopathy. Recently, the scientific community has focused on the multiple genetic and clinical profiles of SCD. However, the lipid composition of sickle cells has received little attention in the literature. According to recent studies, changes in the lipid profile are strongly linked to several disorders. Therefore, the aim of this study is to dig deeper into lipidomic analysis of erythrocytes in order to highlight any variations between healthy and patient subjects. 241 lipid molecular species divided into 17 classes have been annotated and quantified. Lipidomic profiling of SCD patients showed that over 24% of total lipids were altered most of which are phospholipids. In-depth study of significant changes in lipid metabolism can give an indication of the enzymes and genes involved. In a systems biology scenario, these variations can be useful to improve the understanding of the biochemical basis of SCD and to try to make a score system that could be predictive for the severity of clinical manifestations.
Collapse
Affiliation(s)
- Husam B. R. Alabed
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
| | - Paolo Gorello
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
| | - Roberto Maria Pellegrino
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
- Correspondence:
| | - Hovirag Lancioni
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
| | - Roberta La Starza
- Hematology and Bone Marrow Transplantation Unit, Laboratory of Molecular Medicine (CREO), Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
| | - Anna Aurora Taddei
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
| | - Lorena Urbanelli
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
| | - Sandra Buratta
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
| | - Anair Graciela Lema Fernandez
- Hematology and Bone Marrow Transplantation Unit, Laboratory of Molecular Medicine (CREO), Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
| | - Caterina Matteucci
- Hematology and Bone Marrow Transplantation Unit, Laboratory of Molecular Medicine (CREO), Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
| | - Maurizio Caniglia
- Pediatric Oncology-Hematology, Azienda Ospedaliera di Perugia, 06100 Perugia, Italy
| | - Francesco Arcioni
- Pediatric Oncology-Hematology, Azienda Ospedaliera di Perugia, 06100 Perugia, Italy
| | - Cristina Mecucci
- Hematology and Bone Marrow Transplantation Unit, Laboratory of Molecular Medicine (CREO), Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
| | - Carla Emiliani
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
- Centro di Eccellenza sui Materiali Innovativi Nanostrutturati (CEMIN), University of Perugia, Via del Giochetto, 06123 Perugia, Italy
| |
Collapse
|
17
|
Wang T, Pattabiraman PP. Analysis of Lipid Contents in Human Trabecular Meshwork Cells by Multiple Reaction Monitoring (MRM) Profiling Lipidomics. Methods Mol Biol 2023; 2625:291-298. [PMID: 36653651 DOI: 10.1007/978-1-0716-2966-6_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Lipids are among the major constituents of cells and play many important cellular functions. Lipid levels in the trabecular meshwork (TM) aqueous humor outflow pathway play an important role in the maintenance of aqueous humor drainage and intraocular pressure (IOP) homeostasis. Therefore, it is important to characterize the changes in the lipid contents in the aqueous humor outflow pathway tissues to better understand their functional significance in the maintenance of IOP. The multiple reaction monitoring (MRM)-based profiling aids in the analysis of the metabolome as a collection of functional groups and is utilized as an exploratory metabolomics and lipidomics approach. The MRM-based profiling utilizes tandem mass spectrometry experiments carried out on a commercial triple quadrupole mass spectrometer with three aligned quadrupole mass filters (Q1, Q2, and Q3). This screening methodology can be utilized for targeted lipidomics screening. This chapter focuses on the methodology for isolation and culturing of the TM cells, lipid extraction, and the MRM-based lipidomics approach with data analysis.
Collapse
Affiliation(s)
- Ting Wang
- Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA.,Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Padmanabhan Paranji Pattabiraman
- Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA. .,Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
| |
Collapse
|
18
|
Mallah K, Zibara K, Kerbaj C, Eid A, Khoshman N, Ousseily Z, Kobeissy A, Cardon T, Cizkova D, Kobeissy F, Fournier I, Salzet M. Neurotrauma investigation through spatial omics guided by mass spectrometry imaging: Target identification and clinical applications. MASS SPECTROMETRY REVIEWS 2023; 42:189-205. [PMID: 34323300 DOI: 10.1002/mas.21719] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/04/2021] [Accepted: 07/11/2021] [Indexed: 06/13/2023]
Abstract
Traumatic brain injury (TBI) represents one of the major public health concerns worldwide due to the increase in TBI incidence as a result of injuries from daily life accidents such as sports and motor vehicle transportation as well as military-related practices. This type of central nervous system trauma is known to predispose patients to several neurological disorders such as Parkinson's disease, Alzheimer's disease, chronic trauamatic encephalopathy, and age-related Dementia. Recently, several proteomic and lipidomic platforms have been applied on different TBI studies to investigate TBI-related mechanisms that have broadened our understanding of its distinct neuropathological complications. In this study, we provide an updated comprehensive overview of the current knowledge and novel perspectives of the spatially resolved microproteomics and microlipidomics approaches guided by mass spectrometry imaging used in TBI studies and its applications in the neurotrauma field. In this regard, we will discuss the use of the spatially resolved microproteomics and assess the different microproteomic sampling methods such as laser capture microdissection, parafilm assisted microdissection, and liquid microjunction extraction as accurate and precise techniques in the field of neuroproteomics. Additionally, we will highlight lipid profiling applications and their prospective potentials in characterizing molecular processes involved in the field of TBI. Specifically, we will discuss the phospholipid metabolism acting as a precursor for proinflammatory molecules such as eicosanoids. Finally, we will survey the current state of spatial neuroproteomics and microproteomics applications and present the various studies highlighting their findings in these fields.
Collapse
Affiliation(s)
- Khalil Mallah
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
- PRASE, Lebanese University, Beirut, Lebanon
- Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France
| | - Kazem Zibara
- PRASE, Lebanese University, Beirut, Lebanon
- Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Coline Kerbaj
- Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Ali Eid
- Department of Basic Medical Sciences, QU Health, Qatar University, Doha, Qatar
| | - Nour Khoshman
- Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Zahraa Ousseily
- Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Abir Kobeissy
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Tristan Cardon
- Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France
| | - Dasa Cizkova
- Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France
- Center for Experimental and Clinical Regenerative Medicine, University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovakia
| | - Firas Kobeissy
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Isabelle Fournier
- Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France
- Institut Universitaire de France, Paris, France
| | - Michel Salzet
- Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France
- Institut Universitaire de France, Paris, France
| |
Collapse
|
19
|
Busnelli M, Manzini S, Colombo A, Franchi E, Lääperi M, Laaksonen R, Chiesa G. Effect of Diets on Plasma and Aorta Lipidome: A Study in the apoE Knockout Mouse Model. Mol Nutr Food Res 2023; 67:e2200367. [PMID: 36419336 DOI: 10.1002/mnfr.202200367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 09/20/2022] [Indexed: 11/27/2022]
Abstract
SCOPE Specific lipid molecules circulating in plasma at low concentrations have emerged as biomarkers of atherosclerotic risk. The aim of the present study is that of evaluating, in an athero-prone mouse model, how different diets can affect plasma and aorta lipidome. METHODS AND RESULTS Thirty-six apoE knockout mice are divided in three groups and feed 12 weeks with diets differing for cholesterol and fatty acid content. Atherosclerosis is measured at the aortic sinus and aorta. Lipids are quantified in plasma and aorta with mass spectrometry. The cholesterol content of the diets is the main driver of lipid accumulation in plasma and aorta. The fatty acid composition of the diets affects plasma levels both of essential (linoleic acid) and nonessential (myristic and arachidonic acid) ones. Lipidomics show a comparable distribution, in plasma and aorta, of the main lipid components of oxidized LDL, including cholesteryl esters and lysophosphatidylcholines. Interestingly, lactosylceramide, glucosyl/galactosylceramide, and individual ceramide species are found to accumulate in diseased aortic segments. CONCLUSION Both the cholesterol and fatty acid content of the diets profoundly affect plasma lipidome. Aorta lipidome is likewise affected with the accumulation of specific lipids known as markers of atherosclerosis.
Collapse
Affiliation(s)
- Marco Busnelli
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti, 9, Milan, 20133, Italy
| | - Stefano Manzini
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti, 9, Milan, 20133, Italy
| | - Alice Colombo
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti, 9, Milan, 20133, Italy
| | - Elsa Franchi
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti, 9, Milan, 20133, Italy
| | | | - Reijo Laaksonen
- Zora Biosciences Oy, Espoo, 02150, Finland.,Finnish Cardiovascular Research Center, University of Tampere, Tampere, 33520, Finland
| | - Giulia Chiesa
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti, 9, Milan, 20133, Italy
| |
Collapse
|
20
|
Wang W, Song L. Landscape of lipidomics in cardiovascular medicine from 2012 to 2021: A systematic bibliometric analysis and literature review. Medicine (Baltimore) 2022; 101:e32599. [PMID: 36596038 PMCID: PMC9803420 DOI: 10.1097/md.0000000000032599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Lipidomics has shaped our knowledge of how lipids play a central role in cardiovascular diseases (CVD), whereas there is a lack of a summary of existing research findings. This study performed a bibliometric analysis of lipidomics research in cardiovascular medicine to reveal the core countries, institutions, key researchers, important references, major journals, research hotspots and frontiers in this field. From 2012 to 2021, a total of 761 articles were obtained from the Web of Science Core Collection database. There is a steady increase of publications yearly. The United States and China are on the top of the list regarding article output. The institutions with the most publications were the Baker Heart and Diabetes Institute, the Chinese Academy of Sciences and Harvard Medical School. Peter J Meikle was both the most published and most co-cited author. The major journal in this field is Journal of lipid research. Keyword co-occurrence analysis indicated that coronary heart disease, mass spectrometry, risk, fatty acid, and insulin resistance have become hot topics in this field and keyword burst detection suggests that metabolomics, activation, liver, low density lipoprotein are the frontiers of research in recent years. Collectively, lipidomics in CVD is still in its infancy with a steady increase yearly. More in-depth studies in this area are warranted in the future.
Collapse
Affiliation(s)
- Wenting Wang
- Department of Cardiovascular Disease, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, China
- * Correspondence: Wenting Wang, Department of Cardiology, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, 208 Huancheng East Road, Hangzhou 310003, China (e-mail: )
| | - Lei Song
- Beijing University of Chinese Medicine, Beijing, China
| |
Collapse
|
21
|
Randolph CE, Beveridge CH, Iyer S, Blanksby SJ, McLuckey SA, Chopra G. Identification of Monomethyl Branched-Chain Lipids by a Combination of Liquid Chromatography Tandem Mass Spectrometry and Charge-Switching Chemistries. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2022; 33:2156-2164. [PMID: 36218280 PMCID: PMC10173259 DOI: 10.1021/jasms.2c00225] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
While various mass spectrometric approaches have been applied to lipid analysis, unraveling the extensive structural diversity of lipids remains a significant challenge. Notably, these approaches often fail to differentiate between isomeric lipids─a challenge that is particularly acute for branched-chain fatty acids (FAs) that often share similar (or identical) mass spectra to their straight-chain isomers. Here, we utilize charge-switching strategies that combine ligated magnesium dications with deprotonated fatty acid anions. Subsequent activation of these charge inverted anions yields mass spectra that differentiate anteiso-branched- from straight-chain and iso-branched-chain FA isomers with the predictable fragmentation enabling de novo assignment of anteiso branch points. The application of these charge-inversion chemistries in both gas- and solution-phase modalities is demonstrated to assign the position of anteiso-methyl branch-points in FAs and, with the aid of liquid chromatography, can be extended to de novo assignment of additional branching sites via predictable fragmentation patterns as methyl branching site(s) move closer to the carboxyl carbon. The gas-phase approach is shown to be compatible with top-down structure elucidation of complex lipids such as phosphatidylcholines, while the integration of solution-phase charge-inversion with reversed phase liquid chromatography enables separation and unambiguous identification of FA structures within isomeric mixtures. Taken together, the presented charge-switching MS-based technique, in combination with liquid chromatography, enables the structural identification of branched-chain FA without the requirement of authentic methyl-branched FA reference standards.
Collapse
Affiliation(s)
- Caitlin E. Randolph
- Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-2084, USA
| | - Connor H. Beveridge
- Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-2084, USA
| | - Sanjay Iyer
- Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-2084, USA
| | - Stephen J. Blanksby
- Central Analytical Research Facility and the School of Chemistry and Physics, Queensland University of Technology, Brisbane, QLD 4000, Australia
| | - Scott A. McLuckey
- Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-2084, USA
| | - Gaurav Chopra
- Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-2084, USA
- Department of Computer Science (by courtesy), Purdue Institutes of Drug Discovery and Integrative Neuroscience, Purdue Center for Cancer Research, West Lafayette, Indiana, 47907, USA
| |
Collapse
|
22
|
Gutiérrez Y, Fresch M, Scherber C, Brockmeyer J. The lipidome of an omnivorous insect responds to diet composition and social environment. Ecol Evol 2022; 12:e9497. [PMID: 36381391 PMCID: PMC9643132 DOI: 10.1002/ece3.9497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 09/30/2022] [Accepted: 10/20/2022] [Indexed: 11/10/2022] Open
Abstract
Lipids are biomolecules with essential roles in metabolic processes, signaling, and cellular architecture. In this study, we investigated changes in the lipidome of the house cricket Acheta domesticus subjected to diets of different nutritional composition (i.e., protein to carbohydrate ratio) and two distinct social environments (i.e., solitary or in groups). We measured relative abundances of 811 lipid species in whole-body cricket samples using flow injection analysis coupled to tandem mass spectrometry. We assessed differences in the relative abundances of lipid species induced by diet composition and social environment in female and male A. domesticus. Additionally, we performed a functional analysis of the lipids with significant differences using a recently developed database. We found that most differences in the relative abundances of lipid species were explained by sex alone. Furthermore, the lipidome of female A. domesticus was responsive to diet composition. Females fed with the balanced diet had an even higher abundance of lipids involved in lipid storage than their counterparts fed with a protein-rich diet. Interestingly, the male cricket lipidome was not responsive to diet composition. In addition, the social environment did not induce significant changes in the lipid profile neither in female nor in male crickets.
Collapse
Affiliation(s)
- Yeisson Gutiérrez
- Centro de Bioinformática y Biología Computacional de Colombia – BIOSManizalesColombia
| | - Marion Fresch
- Institute for Biochemistry and Technical BiochemistryUniversity of StuttgartStuttgartGermany
| | - Christoph Scherber
- Institute of Landscape EcologyUniversity of MünsterMünsterGermany
- Centre for Biodiversity MonitoringZoological Research Museum Alexander KoenigBonnGermany
| | - Jens Brockmeyer
- Institute for Biochemistry and Technical BiochemistryUniversity of StuttgartStuttgartGermany
| |
Collapse
|
23
|
Cherian G. Hatching egg polyunsaturated fatty acids and the broiler chick. J Anim Sci Biotechnol 2022; 13:98. [PMID: 36117183 PMCID: PMC9484210 DOI: 10.1186/s40104-022-00757-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 07/08/2022] [Indexed: 11/21/2022] Open
Abstract
Transgenerational effects of certain nutrients such as essential fatty acids are gaining increased attention in the field of human medicine and animal sciences as a new tool to improve health and animal performance during perinatal life. Omega-3 (n-3) and omega-6 (n-6) fatty acids are denoted by the position of the first double bond from methyl end of the hydrocarbon chain. Alpha-linolenic acid (18:3 n-3) and linoleic acid (18:2 n-6) are essential n-3 and n-6 fatty acids and cannot be synthesized by the vertebrates including chickens. Alpha-linolenic acid and linoleic acid are the parent fatty acids of long chain (> 20–22C) n-3 and n-6 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (20:5 n-3, EPA), docosapentaenoic acid (22:5 n-3/or 22:5 n-6, DPA), docosahexaenoic acid (22:6 n-3, DHA) and arachidonic acid (20:4 n-6). As components of cell membrane phospholipids, PUFA serves as precursors of eicosanoids, act as ligands for membrane receptors and transcription factors that regulate gene expression and are pivotal for normal chick growth and development. Considering the role of egg lipids as the sole source of essential fatty acids to the hatchling, dietary deficiencies or inadequate in ovo supply may have repercussions in tissue PUFA incorporation, lipid metabolism, chick growth and development during pre and early post-hatch period. This review focus on studies showing how maternal dietary n-3 or n-6 fatty acids can lead to remodeling of long chain n-3 and n-6 PUFA in the hatching egg and progeny chick tissue phospholipid molecular species and its impact on chick growth and PUFA metabolism during early life.
Collapse
|
24
|
Rapid Evaporative Ionization Mass Spectrometry-Based Lipidomics for Identification of Canine Mammary Pathology. Int J Mol Sci 2022; 23:ijms231810562. [PMID: 36142485 PMCID: PMC9502565 DOI: 10.3390/ijms231810562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/02/2022] [Accepted: 09/09/2022] [Indexed: 11/16/2022] Open
Abstract
The present work proposes the use of a fast analytical platform for the mass spectrometric (MS) profiling of canine mammary tissues in their native form for the building of a predictive statistical model. The latter could be used as a novel diagnostic tool for the real-time identification of different cellular alterations in order to improve tissue resection during veterinary surgery, as previously validated in human oncology. Specifically, Rapid Evaporative Ionization Mass Spectrometry (REIMS) coupled with surgical electrocautery (intelligent knife—iKnife) was used to collect MS data from histologically processed mammary samples, classified into healthy, hyperplastic/dysplastic, mastitis and tumors. Differences in the lipid composition enabled tissue discrimination with an accuracy greater than 90%. The recognition capability of REIMS was tested on unknown mammary samples, and all of them were correctly identified with a correctness score of 98–100%. Triglyceride identification was increased in healthy mammary tissues, while the abundance of phospholipids was observed in altered tissues, reflecting morpho-functional changes in cell membranes, and oxidized species were also tentatively identified as discriminant features. The obtained lipidomic profiles represented unique fingerprints of the samples, suggesting that the iKnife technique is capable of differentiating mammary tissues following chemical changes in cellular metabolism.
Collapse
|
25
|
Pranneshraj V, Sangha MK, Djalovic I, Miladinovic J, Djanaguiraman M. Lipidomics-Assisted GWAS (lGWAS) Approach for Improving High-Temperature Stress Tolerance of Crops. Int J Mol Sci 2022; 23:ijms23169389. [PMID: 36012660 PMCID: PMC9409476 DOI: 10.3390/ijms23169389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/08/2022] [Accepted: 08/12/2022] [Indexed: 11/25/2022] Open
Abstract
High-temperature stress (HT) over crop productivity is an important environmental factor demanding more attention as recent global warming trends are alarming and pose a potential threat to crop production. According to the Sixth IPCC report, future years will have longer warm seasons and frequent heat waves. Thus, the need arises to develop HT-tolerant genotypes that can be used to breed high-yielding crops. Several physiological, biochemical, and molecular alterations are orchestrated in providing HT tolerance to a genotype. One mechanism to counter HT is overcoming high-temperature-induced membrane superfluidity and structural disorganizations. Several HT lipidomic studies on different genotypes have indicated the potential involvement of membrane lipid remodelling in providing HT tolerance. Advances in high-throughput analytical techniques such as tandem mass spectrometry have paved the way for large-scale identification and quantification of the enormously diverse lipid molecules in a single run. Physiological trait-based breeding has been employed so far to identify and select HT tolerant genotypes but has several disadvantages, such as the genotype-phenotype gap affecting the efficiency of identifying the underlying genetic association. Tolerant genotypes maintain a high photosynthetic rate, stable membranes, and membrane-associated mechanisms. In this context, studying the HT-induced membrane lipid remodelling, resultant of several up-/down-regulations of genes and post-translational modifications, will aid in identifying potential lipid biomarkers for HT tolerance/susceptibility. The identified lipid biomarkers (LIPIDOTYPE) can thus be considered an intermediate phenotype, bridging the gap between genotype–phenotype (genotype–LIPIDOTYPE–phenotype). Recent works integrating metabolomics with quantitative genetic studies such as GWAS (mGWAS) have provided close associations between genotype, metabolites, and stress-tolerant phenotypes. This review has been sculpted to provide a potential workflow that combines MS-based lipidomics and the robust GWAS (lipidomics assisted GWAS-lGWAS) to identify membrane lipid remodelling related genes and associations which can be used to develop HS tolerant genotypes with enhanced membrane thermostability (MTS) and heat stable photosynthesis (HP).
Collapse
Affiliation(s)
- Velumani Pranneshraj
- Department of Biochemistry, Punjab Agricultural University, Ludhiana 141004, India
| | - Manjeet Kaur Sangha
- Department of Biochemistry, Punjab Agricultural University, Ludhiana 141004, India
| | - Ivica Djalovic
- Institute of Field and Vegetable Crops, National Institute of the Republic of Serbia, Maxim Gorki 30, 21000 Novi Sad, Serbia
- Correspondence: (I.D.); (M.D.)
| | - Jegor Miladinovic
- Institute of Field and Vegetable Crops, National Institute of the Republic of Serbia, Maxim Gorki 30, 21000 Novi Sad, Serbia
| | - Maduraimuthu Djanaguiraman
- Department of Crop Physiology, Tamil Nadu Agricultural University, Coimbatore 641003, India
- Correspondence: (I.D.); (M.D.)
| |
Collapse
|
26
|
Konjevod M, Sáiz J, Nikolac Perkovic M, Nedic Erjavec G, Tudor L, Uzun S, Kozumplik O, Barbas C, Zarkovic N, Pivac N, Strac DS. Plasma lipidomics in subjects with combat posttraumatic stress disorder. Free Radic Biol Med 2022; 189:169-177. [PMID: 35918015 DOI: 10.1016/j.freeradbiomed.2022.07.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/18/2022] [Indexed: 11/18/2022]
Abstract
Posttraumatic stress disorder (PTSD) is complex neuropsychiatric disorder triggered by a traumatic event and characterized by the symptoms that represent large burden to patients, as well as to society. Lipidomic approach can be applied as a useful tool for discovery of novel diagnostic, prognostic and therapeutic lipid biomarkers of various disorders, whose etiology is complex and still unknown, including PTSD. Since changes in the levels of lipid metabolites might indicate impairments in various metabolic pathways and cellular processes, the aim of this lipidomic study was to determine altered levels of lipid compounds in PTSD. The study enrolled 235 male patients with combat PTSD and 241 healthy male control subjects. Targeted lipidomic analysis of plasma samples was conducted using reverse-phase liquid chromatography coupled with mass spectrometry. Lipids that have been analyzed belong to the group of ceramides, cholesterol esters, diacylglycerols, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylethanolamines, sphingomyelins and triglycerides. The levels of fifteen lipid compounds were found to be significantly different between PTSD patients and healthy control subjects, including four phosphatidylcholines, two phosphatidylethanolamines, five sphingomyelins, two cholesterol esters and two ceramides. The lipid metabolites whose levels significantly differed between patients with PTSD and control subjects are associated with various biological processes, including impairments of membrane integrity and function, mitochondrial dysfunction, inflammation and oxidative stress. As these processes might be associated with development and progression of PTSD, altered lipid compounds represent potential biomarkers that could facilitate the diagnosis of PTSD, prediction of the disease, as well as identification of novel treatment approaches in PTSD.
Collapse
Affiliation(s)
- Marcela Konjevod
- Ruder Boskovic Institute, Division of Molecular Medicine, Bijenicka Cesta 54, 10000, Zagreb, Croatia; Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizacion Monteprincipe, 28660, Boadilla del Monte, Spain
| | - Jorge Sáiz
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizacion Monteprincipe, 28660, Boadilla del Monte, Spain.
| | - Matea Nikolac Perkovic
- Ruder Boskovic Institute, Division of Molecular Medicine, Bijenicka Cesta 54, 10000, Zagreb, Croatia
| | - Gordana Nedic Erjavec
- Ruder Boskovic Institute, Division of Molecular Medicine, Bijenicka Cesta 54, 10000, Zagreb, Croatia
| | - Lucija Tudor
- Ruder Boskovic Institute, Division of Molecular Medicine, Bijenicka Cesta 54, 10000, Zagreb, Croatia
| | - Suzana Uzun
- Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapce, Bolnicka Cesta 32, 10000, Zagreb, Croatia; School of Medicine, University of Zagreb, Salata 2, 10 000, Zagreb, Croatia; Faculty of Education and Rehabilitation Studies, University of Zagreb, University Campus Borongaj, Borongajska Cesta 83f, 10000, Zagreb, Croatia
| | - Oliver Kozumplik
- Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapce, Bolnicka Cesta 32, 10000, Zagreb, Croatia; Faculty of Education and Rehabilitation Studies, University of Zagreb, University Campus Borongaj, Borongajska Cesta 83f, 10000, Zagreb, Croatia
| | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizacion Monteprincipe, 28660, Boadilla del Monte, Spain
| | - Neven Zarkovic
- Ruder Boskovic Institute, Division of Molecular Medicine, Bijenicka Cesta 54, 10000, Zagreb, Croatia
| | - Nela Pivac
- Ruder Boskovic Institute, Division of Molecular Medicine, Bijenicka Cesta 54, 10000, Zagreb, Croatia.
| | - Dubravka Svob Strac
- Ruder Boskovic Institute, Division of Molecular Medicine, Bijenicka Cesta 54, 10000, Zagreb, Croatia.
| |
Collapse
|
27
|
Alvi T, Khan MKI, Maan AA, Razzaq ZU. Date fruit as a promising source of functional carbohydrates and bioactive compounds: A review on its nutraceutical potential. J Food Biochem 2022; 46:e14325. [PMID: 35894233 DOI: 10.1111/jfbc.14325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/14/2022] [Indexed: 11/28/2022]
Abstract
From the past decade, consumption of ready-to-eat food and ease of access to fast food increased the onset of several diseases. Thus, there is a need to shift the trend from consumption of unhealthy food item to natural and healthy alternatives. In this context, fruits can be considered as functional food, which have ability to provide essential nutrients and bioactive compounds. These compounds when consume in adequate amount would have the potential to lower the onset of diseases. In this regard, Phoenix dactylifera or date fruit is an important source of functional carbohydrates and bioactive compounds for their use as functional foods. The major functional carbohydrate in date fruit are in the form of dietary fiber, such as β-glucan, cellulose and fructans along with other bioactive compounds. Additionally, it is also a good source of other important nutrients such as sugars, minerals, along with minor quantities of proteins and lipids. Due to these functional compounds, date fruit have shown a wide range of pharmaceutical properties such as antioxidant, anti-inflammatory, anti-diabetic, hepatoprotective and anticancer. This review provides latest information regarding functional and nutraceutical carbohydrates of date fruits along-with mechanism of action on different diseases reported in recent years. PRACTICAL APPLICATIONS: This will provide information to food industries for the development of innovative food products by using date fruit. Moreover, bioactive components from date fruit may prove to enhance global health and wellness. However, further research is needed on clinical trials for the development of functional food products by using date fruit for functional foods and pharmaceutical applications.
Collapse
Affiliation(s)
- Tayyaba Alvi
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| | - Muhammad Kashif Iqbal Khan
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan.,Department of Food Engineering, University of Agriculture, Faisalabad, Pakistan
| | - Abid Aslam Maan
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan.,Department of Food Engineering, University of Agriculture, Faisalabad, Pakistan
| | - Zafar Ullah Razzaq
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| |
Collapse
|
28
|
Ruiz-Hernández IM, Nouri MZ, Kozuch M, Denslow ND, Díaz-Gamboa RE, Rodríguez-Canul R, Collí-Dulá RC. Trace element and lipidomic analysis of bottlenose dolphin blubber from the Yucatan coast: Lipid composition relationships. CHEMOSPHERE 2022; 299:134353. [PMID: 35314180 DOI: 10.1016/j.chemosphere.2022.134353] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/27/2022] [Accepted: 03/15/2022] [Indexed: 06/14/2023]
Abstract
Bottlenose dolphins (Tursiops truncatus) are found in coastal and estuarine ecosystems where they are in continuous contact with multiple abiotic and biotic stressors in the environment. Due to their role as predators, they can bioaccumulate contaminants and are considered sentinel organisms for monitoring the health of coastal marine ecosystems. The northern zonal coast of the Yucatan peninsula of Mexico has a high incidence of anthropogenic activities. The principal objectives of this study were two-fold: 1) to determine the presence of trace metals and their correlation with lipids in bottlenose dolphin blubber, and 2) to use a lipidomics approach to characterize their biological responses. Levels of trace elements (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Pb) were analyzed using ICP-MS and lipids were measured using a targeted lipidomics approach with LC-MS/MS. Spearman correlation analysis was used to identify associations between lipids and trace elements. The influences of gender, stranding codes, presence of stomach content, growth stages and body length were also analyzed. Blubber lipid composition was dominated by triacylglycerols (TAG). Our results demonstrated the presence of heavy-metal elements such as Cd and As, which were correlated with different lipid species, mainly the ceramides and glycerophospholipids, respectively. Organisms with Cd showed lower concentrations of ceramides (CER, HCER and DCER), TAG and cholesteryl esters (CE). Trace elements Cr, Co, As and Cd increased proportionately with body length. This study provides a novel insight of lipidomic characterization and correlations with trace elements in the bottlenose dolphin which might contribute to having a better understanding of the physiological functions and the risks that anthropogenic activities can bring to sentinel organisms from coastal regions.
Collapse
Affiliation(s)
- Ixchel M Ruiz-Hernández
- Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Mérida. Antigua Carretera a Progreso km 6. Cordemex, Mérida, Yucatán, 97310, Mexico.
| | - Mohammad-Zaman Nouri
- Department of Physiological Sciences and Center for Environmental and Human Toxicology. University of Florida. PO Box 110885. 2187 Mowry Road. Gainesville, FL, 32611, USA.
| | - Marianne Kozuch
- Department of Physiological Sciences and Center for Environmental and Human Toxicology. University of Florida. PO Box 110885. 2187 Mowry Road. Gainesville, FL, 32611, USA.
| | - Nancy D Denslow
- Department of Physiological Sciences and Center for Environmental and Human Toxicology. University of Florida. PO Box 110885. 2187 Mowry Road. Gainesville, FL, 32611, USA.
| | - Raúl E Díaz-Gamboa
- Universidad Autónoma de Yucatán, Departamento de Biología Marina, Mérida, Yucatán, 97000, Mexico.
| | - Rossanna Rodríguez-Canul
- Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Mérida. Antigua Carretera a Progreso km 6. Cordemex, Mérida, Yucatán, 97310, Mexico.
| | - Reyna C Collí-Dulá
- Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Mérida. Antigua Carretera a Progreso km 6. Cordemex, Mérida, Yucatán, 97310, Mexico; CONACYT, CONACYT, Ciudad de México, Mexico.
| |
Collapse
|
29
|
Chatterjee A, Sakallioglu IT, Murthy D, Kosmacek EA, Singh PK, McDonald JT, Powers R, Oberley-Deegan RE. MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure. Redox Biol 2022; 52:102301. [PMID: 35358851 PMCID: PMC8967707 DOI: 10.1016/j.redox.2022.102301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/04/2022] [Accepted: 03/21/2022] [Indexed: 11/20/2022] Open
Abstract
Radiation is a common anticancer therapy for prostate cancer, which transforms tumor-associated normal fibroblasts to myofibroblasts, resulting in fibrosis. Oxidative stress caused by radiation-mediated mitochondrial damage is one of the major contributors to fibrosis. As diabetics are oxidatively stressed, radiation-mediated reactive oxygen species cause severe treatment failure, treatment-related side effects, and significantly reduced survival for diabetic prostate cancer patients as compared to non-diabetic prostate cancer patients. Hyperglycemia and enhanced mitochondrial damage significantly contribute to oxidative damage and disease progression after radiation therapy among diabetic prostate cancer patients. Therefore, reduction of mitochondrial damage in normal prostate fibroblasts after radiation should improve the overall clinical state of diabetic prostate cancer patients. We previously reported that MnTE-2-PyP, a manganese porphyrin, reduces oxidative damage in irradiated hyperglycemic prostate fibroblasts by scavenging superoxide and activating NRF2. In the current study, we have investigated the potential role of MnTE-2-PyP to protect mitochondrial health in irradiated hyperglycemic prostate fibroblasts. This study revealed that hyperglycemia and radiation increased mitochondrial ROS via blocking the mitochondrial electron transport chain, altered mitochondrial dynamics, and reduced mitochondrial biogenesis. Increased mitochondrial damage preceeded an increase in myofibroblast differentiation. MnTE-2-PyP reduced myofibroblast differentiation, improved mitochondrial health by releasing the block on the mitochondrial electron transport chain, enhanced ATP production efficiency, and restored mitochondrial dynamics and metabolism in the irradiated-hyperglycemic prostate fibroblasts. Therefore, we are proposing that one of the mechanisms that MnTE-2-PyP protects prostate fibroblasts from irradiation and hyperglycemia-mediated damage is by protecting the mitochondrial health in diabetic prostate cancer patients.
Collapse
Affiliation(s)
- Arpita Chatterjee
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Isin T Sakallioglu
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA
| | - Divya Murthy
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Elizabeth A Kosmacek
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Pankaj K Singh
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - J Tyson McDonald
- Department of Physics & Cancer Research Center, Hampton University, Hampton, VA, 23668, USA
| | - Robert Powers
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA; Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA
| | - Rebecca E Oberley-Deegan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
| |
Collapse
|
30
|
de Almeida FC, Berzoti-Coelho MG, Toro DM, Cacemiro MDC, Bassan VL, Barretto GD, Garibaldi PMM, Palma LC, de Figueiredo-Pontes LL, Sorgi CA, Faciolli LH, Gardinassi LG, de Castro FA. Bioactive Lipids as Chronic Myeloid Leukemia’s Potential Biomarkers for Disease Progression and Response to Tyrosine Kinase Inhibitors. Front Immunol 2022; 13:840173. [PMID: 35493444 PMCID: PMC9043757 DOI: 10.3389/fimmu.2022.840173] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/15/2022] [Indexed: 01/04/2023] Open
Abstract
Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that expresses the Philadelphia chromosome and constitutively activated Bcr-Abl tyrosine kinase in hematopoietic progenitor cells. Bcr-Abl tyrosine-kinase inhibitors (TKI) do not definitively cure all CML patients. The efficacy of TKI is reduced in CML patients in the blastic phase—the most severe phase of the disease—and resistance to this drug has emerged. There is limited knowledge on the underlying mechanisms of disease progression and resistance to TKI beyond BCR-ABL1, as well as on the impact of TKI treatment and disease progression on the metabolome of CML patients. The present study reports the metabolomic profiles of CML patients at different phases of the disease treated with TKI. The plasma metabolites from CML patients were analyzed using liquid chromatography, mass spectrometry, and bioinformatics. Distinct metabolic patterns were identified for CML patients at different phases of the disease and for those who were resistant to TKI. The lipid metabolism in CML patients at advanced phases and TKI-resistant patients is reprogrammed, as detected by analysis of metabolomic data. CML patients who were responsive and resistant to TKI therapy exhibited distinct enriched pathways. In addition, ceramide levels were higher and sphingomyelin levels were lower in resistant patients compared with control and CML groups. Taken together, the results here reported established metabolic profiles of CML patients who progressed to advanced phases of the disease and failed to respond to TKI therapy as well as patients in remission. In the future, an expanded study on CML metabolomics may provide new potential prognostic markers for disease progression and response to therapy.
Collapse
MESH Headings
- Biomarkers
- Disease Progression
- Drug Resistance, Neoplasm/genetics
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
- Lipids/therapeutic use
- Protein Kinase Inhibitors/pharmacology
- Protein Kinase Inhibitors/therapeutic use
Collapse
Affiliation(s)
- Felipe Campos de Almeida
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
- *Correspondence: Felipe Campos de Almeida, ; Fabíola Attié de Castro,
| | - Maria G. Berzoti-Coelho
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Diana Mota Toro
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
- Biological Science Institute, Department of Basic and Applied Immunology at Manaus Federal University, Manaus, Brazil
| | - Maira da Costa Cacemiro
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Vitor Leonardo Bassan
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Gabriel Dessotti Barretto
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Pedro Manoel Marques Garibaldi
- Division of Hematology, Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Leonardo Carvalho Palma
- Division of Hematology, Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Lorena Lobo de Figueiredo-Pontes
- Division of Hematology, Department of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Carlos Arterio Sorgi
- Chemistry Department, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Lucia Helena Faciolli
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Luiz Gustavo Gardinassi
- Department of Biosciences and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiania, Brazil
| | - Fabíola Attié de Castro
- Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
- Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- *Correspondence: Felipe Campos de Almeida, ; Fabíola Attié de Castro,
| |
Collapse
|
31
|
Han X, Gross RW. The foundations and development of lipidomics. J Lipid Res 2022; 63:100164. [PMID: 34953866 PMCID: PMC8953652 DOI: 10.1016/j.jlr.2021.100164] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 12/15/2022] Open
Abstract
For over a century, the importance of lipid metabolism in biology was recognized but difficult to mechanistically understand due to the lack of sensitive and robust technologies for identification and quantification of lipid molecular species. The enabling technological breakthroughs emerged in the 1980s with the development of soft ionization methods (Electrospray Ionization and Matrix Assisted Laser Desorption/Ionization) that could identify and quantify intact individual lipid molecular species. These soft ionization technologies laid the foundations for what was to be later named the field of lipidomics. Further innovative advances in multistage fragmentation, dramatic improvements in resolution and mass accuracy, and multiplexed sample analysis fueled the early growth of lipidomics through the early 1990s. The field exponentially grew through the use of a variety of strategic approaches, which included direct infusion, chromatographic separation, and charge-switch derivatization, which facilitated access to the low abundance species of the lipidome. In this Thematic Review, we provide a broad perspective of the foundations, enabling advances, and predicted future directions of growth of the lipidomics field.
Collapse
Affiliation(s)
- Xianlin Han
- Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Departments of Medicine - Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
| | - Richard W Gross
- Division of Bioorganic Chemistry and Molecular Pharmacology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Chemistry, Washington University, St. Louis, MO, USA
| |
Collapse
|
32
|
Zhao L, Han L, Wei X, Zhou Y, Zhang Y, Si N, Wang H, Yang J, Bian B, Zhao H. Toxicokinetics of Arenobufagin and its Cardiotoxicity Mechanism Exploration Based on Lipidomics and Proteomics Approaches in Rats. Front Pharmacol 2022; 12:780016. [PMID: 35002716 PMCID: PMC8727535 DOI: 10.3389/fphar.2021.780016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 11/22/2021] [Indexed: 12/17/2022] Open
Abstract
Arenobufagin (ArBu), one of the main active bufadienolides of toad venom with cardiotonic effect, analgesic effect, and outstanding anti-tumor potentiality, is also a potential cardiotoxic component. In the present study, the cardiac effect of ArBu and its underlying mechanism were explored by integrating data such as heart rates, toxicokinetics, myocardial enzyme and brain natriuretic peptide (BNP) activity, pathological sections, lipidomics and proteomics. Under different doses, the cardiac effects turned out to be different. The oral dose of 60 mg/kg of ArBu sped up the heart rate. However, 120 mg/kg ArBu mainly reduced the heart rate. Over time, they all returned to normal, consisting of the trend of ArBu concentration-time curve. High concentrations of myocardial enzymes and BNP indicated that ArBu inhibited or impaired the cardiac function of rats. Pathological sections of hearts also showed that ArBu caused myocardial fiber disorder and rupture, in which the high-dose group was more serious. At the same time, serum and heart tissue lipidomics were used to explore the changes in body lipid metabolism under different doses. The data indicated a larger difference in the high-dose ArBu group. There were likewise many significant differences in the proteomics of the heart. Furthermore, a multi-layered network was used to integrate the above information to explore the potential mechanism. Finally, 4 proteins that were shown to be significantly and differentially expressed were validated by targeted proteomics using parallel reaction monitoring (PRM) analysis. Our findings indicated that ArBu behaved as a bidirectional regulation of the heart. The potential mechanism of cardiac action was revealed with the increased dose, which provided a useful reference for the safety of clinical application of ArBu.
Collapse
Affiliation(s)
- Lijuan Zhao
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.,Shaanxi Chinese Medicine Institute (Shaanxi Pharmaceutical Information Center), Xianyang, China
| | - Lingyu Han
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.,School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Xiaolu Wei
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanyan Zhou
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanqiong Zhang
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Nan Si
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hongjie Wang
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jian Yang
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Baolin Bian
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haiyu Zhao
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| |
Collapse
|
33
|
Singh RS, Angra V, Singh A, Masih GD, Medhi B. Integrative omics - An arsenal for drug discovery. Indian J Pharmacol 2022; 54:1-6. [PMID: 35343200 PMCID: PMC9012413 DOI: 10.4103/ijp.ijp_53_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Affiliation(s)
- Rahul Soloman Singh
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vani Angra
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashutosh Singh
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Gladson David Masih
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Bikash Medhi
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
34
|
Liu J, Li T, Pei W, Zhao Y, Zhang X, Shi X, Li Y, Xu W. Lipidomics reveals the dysregulated ceramide metabolism in oxidized low-density lipoprotein-induced macrophage-derived foam cell. Biomed Chromatogr 2021; 36:e5297. [PMID: 34893994 DOI: 10.1002/bmc.5297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 10/01/2021] [Accepted: 11/23/2021] [Indexed: 12/12/2022]
Abstract
Atherosclerosis (AS) is associated with increasing lipid peroxidation. Oxidative modification of low-density lipoproteins (ox-LDL) is one most important factors contributing to the pathogenesis and clinical features of AS. The lipid composition influenced by ox-LDL is not known clearly. In this work, a UHPLC/Orbitrap MS-based lipidomics approach integrated pathway analysis was performed to advance understanding of the lipid composition and feature pathway in an ox-LDL-induced foamy macrophage cell. In the lipid metabolic profiling, 196 lipid species from 15 (sub)classes were identified. Lipid profiling indicated that increasing ox-LDL caused lipid metabolic alternations, manifesting as phospholipids being down-regulated and sphingolipids being up-regulated. Pathway analysis explored glycerophospholipid and sphingolipid metabolism, which was involved in atherogenic changes. Notably, dysregulated ceramide metabolism was a typical feature of foamy cell formation. qRT-PCR analysis was conducted to explore the differentially expressed genes. It indicated that ceramide metabolic balance might be disordered, performing higher synthesis and lower hydrolysis, with the ratio of SMPD1/SGMS2 being significantly up-regulated (p < 0.05) in the ox-LDL induced group. Our work offers a comprehensive understanding of macrophage-derived foam cells and screen feature pathways associated with foamy cell formation, which provides a reference for the clinic diagnosis of AS and drug interventions.
Collapse
Affiliation(s)
- Jie Liu
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Tong Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Wenxuan Pei
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Ye Zhao
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Xin Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiujia Shi
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yanping Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Wenjuan Xu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| |
Collapse
|
35
|
Díaz de León-Martínez L, Flores-Ramírez R, López-Mendoza CM, Rodríguez-Aguilar M, Metha G, Zúñiga-Martínez L, Ornelas-Rebolledo O, Alcántara-Quintana LE. Identification of volatile organic compounds in the urine of patients with cervical cancer. Test concept for timely screening. Clin Chim Acta 2021; 522:132-140. [PMID: 34418363 DOI: 10.1016/j.cca.2021.08.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/19/2021] [Accepted: 08/13/2021] [Indexed: 01/15/2023]
Abstract
The objective of this research was to identify a global chemical pattern of volatile organic compounds (VOCs) in urine capable of discriminating between women with cervical cancer (CC) and control women using an electronic nose and to elucidate potential biomarkers by gas chromatography-mass spectrometry (GC-MS). A cross-sectional study was performed, with 12 control women, 5 women with CIN (Cervical Intraepithelial Neoplasia) and 12 women with CC. Global VOCs in urine were assessed using an electronic nose and specific by GC-MS. Multivariate analysis was performed: Principal Component Analysis (PCA), Canonical Principal Coordinate Analysis (CAP) and Partial Least Squares Discriminant Analysis (PLS-DA) and the test's diagnostic power was evaluated through ROC (Receiver Operating Characteristic) curves. Results from the PCA between the control group compared to the CC present variability of 98.4% (PC1 = 93.9%, PC2 = 2.3% and PC3 = 2.1%). CAP model shows a separation between the overall VOCs profile of the control and CC group with a correct classification of 94.7%. PLS-DA indicated that 8 sensors have a higher contribution in the CC group. The sensitivity, specificity, value reached 91.6% (61.5%-99.7%) and 100% (73.5%-100%) respectively, according to the ROC curve. GC-MS analysis indicated that 33 compounds occur only in the CC group and some of them have been found in other types of cancer. In all, this study provides the basis for the development of an accessible, non-invasive, sensitive and specific screening platform for cervical cancer through the application of electronic nose and chemometric analysis.
Collapse
Affiliation(s)
- Lorena Díaz de León-Martínez
- Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Avenida Sierra Leona No. 550, CP 78210, Colonia Lomas Segunda Sección, San Luis Potosí, SLP, México
| | - Rogelio Flores-Ramírez
- Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Avenida Sierra Leona No. 550, CP 78210, Colonia Lomas Segunda Sección, San Luis Potosí, SLP, México.
| | - Carlos Miguel López-Mendoza
- Unidad de Innovación en Diagnóstico Celular y Molecular. Coordinación para la Innovación y la Aplicación de la Ciencia y Tecnología, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona 550, Lomas 2a sección, 78120 San Luis Potosí, México
| | | | - Garima Metha
- CEO of Altus Lifescience, San José, CA, United States
| | - Lourdes Zúñiga-Martínez
- Unidad de Innovación en Diagnóstico Celular y Molecular. Coordinación para la Innovación y la Aplicación de la Ciencia y Tecnología, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona 550, Lomas 2a sección, 78120 San Luis Potosí, México
| | - Omar Ornelas-Rebolledo
- Labinnova Center of Research in Breath for early diseases detection, Guadalajara, Mexico
| | - Luz Eugenia Alcántara-Quintana
- Unidad de Innovación en Diagnóstico Celular y Molecular. Coordinación para la Innovación y la Aplicación de la Ciencia y Tecnología, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona 550, Lomas 2a sección, 78120 San Luis Potosí, México.
| |
Collapse
|
36
|
Altered metabolic pathways elucidated via untargeted in vivo toxicometabolomics in rat urine and plasma samples collected after controlled application of a human equivalent amphetamine dose. Arch Toxicol 2021; 95:3223-3234. [PMID: 34414480 PMCID: PMC8448701 DOI: 10.1007/s00204-021-03135-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/11/2021] [Indexed: 10/28/2022]
Abstract
Amphetamine is widely consumed as drug of abuse due to its stimulating and cognitive enhancing effects. Since amphetamine has been on the market for quite a long time and it is one of the most commonly used stimulants worldwide, to date there is still limited information on its effects on the metabolome. In recent years, untargeted toxicometabolomics have been increasingly used to study toxicity-related pathways of such drugs of abuse to find and identify important endogenous and exogenous biomarkers. In this study, the acute effects of amphetamine intake on plasma and urinary metabolome in rats were investigated. For this purpose, samples of male Wistar rats after a single dose of amphetamine (5 mg/kg) were compared to a control group using an untargeted metabolomics approach. Analysis was performed using normal and reversed phase liquid chromatography coupled to high-resolution mass spectrometry using positive and negative ionization mode. Statistical evaluation was performed using Welch's two-sample t test, hierarchical clustering, as well as principal component analysis. The results of this study demonstrate a downregulation of amino acids in plasma samples after amphetamine exposure. Furthermore, four new potential biomarkers N-acetylamphetamine, N-acetyl-4-hydroxyamphetamine, N-acetyl-4-hydroxyamphetamine glucuronide, and amphetamine succinate were identified in urine. The present study complements previous data and shows that several studies are necessary to elucidate altered metabolic pathways associated with acute amphetamine exposure.
Collapse
|
37
|
Abstract
Lipids are natural substances found in all living organisms and involved in many biological functions. Imbalances in the lipid metabolism are linked to various diseases such as obesity, diabetes, or cardiovascular disease. Lipids comprise thousands of chemically distinct species making them a challenge to analyze because of their great structural diversity.Thanks to the technological improvements in the fields of chromatography, high-resolution mass spectrometry, and bioinformatics over the last years, it is now possible to perform global lipidomics analyses, allowing the concomitant detection, identification, and relative quantification of hundreds of lipid species. This review shall provide an insight into a general lipidomics workflow and its application in metabolic biomarker research.
Collapse
|
38
|
The Importance of Lipidomic Approach for Mapping and Exploring the Molecular Networks Underlying Physical Exercise: A Systematic Review. Int J Mol Sci 2021; 22:ijms22168734. [PMID: 34445440 PMCID: PMC8395903 DOI: 10.3390/ijms22168734] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 02/07/2023] Open
Abstract
Maintaining appropriate levels of physical exercise is an optimal way for keeping a good state of health. At the same time, optimal exercise performance necessitates an integrated organ system response. In this respect, physical exercise has numerous repercussions on metabolism and function of different organs and tissues by enhancing whole-body metabolic homeostasis in response to different exercise-related adaptations. Specifically, both prolonged and intensive physical exercise produce vast changes in multiple and different lipid-related metabolites. Lipidomic technologies allow these changes and adaptations to be clarified, by using a biological system approach they provide scientific understanding of the effect of physical exercise on lipid trajectories. Therefore, this systematic review aims to indicate and clarify the identifying biology of the individual response to different exercise workloads, as well as provide direction for future studies focused on the body’s metabolome exercise-related adaptations. It was performed using five databases (Medline (PubMed), Google Scholar, Embase, Web of Science, and Cochrane Library). Two author teams reviewed 105 abstracts for inclusion and at the end of the screening process 50 full texts were analyzed. Lastly, 14 research articles specifically focusing on metabolic responses to exercise in healthy subjects were included. The Oxford quality scoring system scale was used as a quality measure of the reviews. Information was extracted using the participants, intervention, comparison, outcomes (PICOS) format. Despite that fact that it is well-known that lipids are involved in different sport-related changes, it is unclear what types of lipids are involved. Therefore, we analyzed the characteristic lipid species in blood and skeletal muscle, as well as their alterations in response to chronic and acute exercise. Lipidomics analyses of the studies examined revealed medium- and long-chain fatty acids, fatty acid oxidation products, and phospholipids qualitative changes. The main cumulative evidence indicates that both chronic and acute bouts of exercise determine significant changes in lipidomic profiles, but they manifested in very different ways depending on the type of tissue examined. Therefore, this systematic review may offer the possibility to fully understand the individual lipidomics exercise-related response and could be especially important to improve athletic performance and human health.
Collapse
|
39
|
Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology. Proc Natl Acad Sci U S A 2021; 118:2104411118. [PMID: 34260388 DOI: 10.1073/pnas.2104411118] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.
Collapse
|
40
|
Function and therapeutic potential of N-acyl amino acids. Chem Phys Lipids 2021; 239:105114. [PMID: 34217720 DOI: 10.1016/j.chemphyslip.2021.105114] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 06/06/2021] [Accepted: 06/29/2021] [Indexed: 12/11/2022]
Abstract
N-acyl amino acids (NAAs) are amphiphilic molecules, with different potential fatty acid and head group moieties. NAAs are the largest family of anandamide congener lipids discovered to date. In recent years, several NAAs have been identified as potential ligands, engaging novel binding sites and mechanisms for modulation of membrane proteins such as G-protein coupled receptors (GPRs), nuclear receptors, ion channels, and transporters. NAAs play a key role in a variety of physiological functions as lipid signaling molecules. Understanding the structure, function roles, and pharmacological potential of these NAAs is still in its infancy, and the biochemical roles are also mostly unknown. This review will provide a summary of the literature on NAAs and emphasize their therapeutic potential.
Collapse
|
41
|
Combined Lipidomics and Network Pharmacology Study of Protective Effects of Salvia miltiorrhiza against Blood Stasis Syndrome. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5526778. [PMID: 33790973 PMCID: PMC7997765 DOI: 10.1155/2021/5526778] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 03/01/2021] [Accepted: 03/11/2021] [Indexed: 12/23/2022]
Abstract
Blood stasis syndrome (BSS) is one of the most common symptoms of cardiovascular diseases (CVDs) in traditional Chinese medicine (TCM) theory. Previous studies have identified that Salvia miltiorrhiza (Danshen) has beneficial effects on BSS, but there is no relevant research from the perspective of lipidomics to study the mechanism of Danshen against BSS since hyperlipidemia has been the widely accepted risk factor of CVDs. In this study, lipidomics technology combined with network pharmacology was applied to investigate the pathological mechanism of BSS and the protective effects of Danshen. The lipidomics profiling based on the UPLC-QTOF-MS analysis method was applied to identify the differential metabolites in the plasma of blood stasis rats. The related pathway and potential targets involved in the anti-BSS effects of Danshen were predicted by pathway analysis and network pharmacology. The biochemical results showed that Danshen intervention significantly reduced whole blood viscosity (WBV) at all the shear rates and fibrinogen concentration (FIB) (p < 0.01) and increased activated partial thromboplastin time (APTT) effectively (p < 0.01). We also found that 52 lipid metabolites, including glycerophospholipid, sphingolipid, glycerolipid, plasmalogen, cholesterol ester, and testosterone, were associated with blood stasis. Moreover, Dgka, Hsd17b3, Hsd3b1, Inppl1, Lpl, Pik3ca, Pik3r1, Pla2g1b, Pla2g2a, Soat1, and Soat2 were predicted as potential targets, while glycerophospholipid metabolism, glycerolipid metabolism, steroid and steroid hormone biosynthesis, phosphatidylinositol signaling system, and ether lipid metabolism were involved as shared critical pathways of lipidomics analysis and network pharmacology. Collectively, this study offered a new understanding of the protection mechanism of Danshen against BSS, which provided new insight to explore the protective effects of Danshen.
Collapse
|
42
|
Properties of Solanum melongena green calyx against toxic effects of diabetes‐induced testopathy: a stereological and biochemical study. ADVANCES IN TRADITIONAL MEDICINE 2021. [DOI: 10.1007/s13596-021-00568-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
|
43
|
Matsushita Y, Nakagawa H, Koike K. Lipid Metabolism in Oncology: Why It Matters, How to Research, and How to Treat. Cancers (Basel) 2021; 13:474. [PMID: 33530546 PMCID: PMC7865757 DOI: 10.3390/cancers13030474] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 12/11/2022] Open
Abstract
Lipids in our body, which are mainly composed of fatty acids, triacylglycerides, sphingolipids, phospholipids, and cholesterol, play important roles at the cellular level. In addition to being energy sources and structural components of biological membranes, several types of lipids serve as signaling molecules or secondary messengers. Metabolic reprogramming has been recognized as a hallmark of cancer, but changes in lipid metabolism in cancer have received less attention compared to glucose or glutamine metabolism. However, recent innovations in mass spectrometry- and chromatography-based lipidomics technologies have increased our understanding of the role of lipids in cancer. Changes in lipid metabolism, so-called "lipid metabolic reprogramming", can affect cellular functions including the cell cycle, proliferation, growth, and differentiation, leading to carcinogenesis. Moreover, interactions between cancer cells and adjacent immune cells through altered lipid metabolism are known to support tumor growth and progression. Characterization of cancer-specific lipid metabolism can be used to identify novel metabolic targets for cancer treatment, and indeed, several clinical trials are currently underway. Thus, we discuss the latest findings on the roles of lipid metabolism in cancer biology and introduce current advances in lipidomics technologies, focusing on their applications in cancer research.
Collapse
Affiliation(s)
| | - Hayato Nakagawa
- Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; (Y.M.); (K.K.)
| | | |
Collapse
|
44
|
"Omics" in traumatic brain injury: novel approaches to a complex disease. Acta Neurochir (Wien) 2021; 163:2581-2594. [PMID: 34273044 PMCID: PMC8357753 DOI: 10.1007/s00701-021-04928-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 06/23/2021] [Indexed: 11/12/2022]
Abstract
BACKGROUND To date, there is neither any pharmacological treatment with efficacy in traumatic brain injury (TBI) nor any method to halt the disease progress. This is due to an incomplete understanding of the vast complexity of the biological cascades and failure to appreciate the diversity of secondary injury mechanisms in TBI. In recent years, techniques for high-throughput characterization and quantification of biological molecules that include genomics, proteomics, and metabolomics have evolved and referred to as omics. METHODS In this narrative review, we highlight how omics technology can be applied to potentiate diagnostics and prognostication as well as to advance our understanding of injury mechanisms in TBI. RESULTS The omics platforms provide possibilities to study function, dynamics, and alterations of molecular pathways of normal and TBI disease states. Through advanced bioinformatics, large datasets of molecular information from small biological samples can be analyzed in detail and provide valuable knowledge of pathophysiological mechanisms, to include in prognostic modeling when connected to clinically relevant data. In such a complex disease as TBI, omics enables broad categories of studies from gene compositions associated with susceptibility to secondary injury or poor outcome, to potential alterations in metabolites following TBI. CONCLUSION The field of omics in TBI research is rapidly evolving. The recent data and novel methods reviewed herein may form the basis for improved precision medicine approaches, development of pharmacological approaches, and individualization of therapeutic efforts by implementing mathematical "big data" predictive modeling in the near future.
Collapse
|
45
|
Khomtchouk BB, Tran DT, Vand KA, Might M, Gozani O, Assimes TL. Cardioinformatics: the nexus of bioinformatics and precision cardiology. Brief Bioinform 2020; 21:2031-2051. [PMID: 31802103 PMCID: PMC7947182 DOI: 10.1093/bib/bbz119] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 08/08/2019] [Accepted: 08/13/2019] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide, causing over 17 million deaths per year, which outpaces global cancer mortality rates. Despite these sobering statistics, most bioinformatics and computational biology research and funding to date has been concentrated predominantly on cancer research, with a relatively modest footprint in CVD. In this paper, we review the existing literary landscape and critically assess the unmet need to further develop an emerging field at the multidisciplinary interface of bioinformatics and precision cardiovascular medicine, which we refer to as 'cardioinformatics'.
Collapse
Affiliation(s)
- Bohdan B Khomtchouk
- Department of Biology, Stanford University, Stanford, CA, USA
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA
- VA Palo Alto Health Care System, Palo Alto, CA, USA
- Department of Medicine, Section of Computational Biomedicine and Biomedical Data Science, University of Chicago, Chicago, IL, USA
| | - Diem-Trang Tran
- School of Computing, University of Utah, Salt Lake City, UT, USA
| | | | - Matthew Might
- Hugh Kaul Personalized Medicine Institute, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Or Gozani
- Department of Biology, Stanford University, Stanford, CA, USA
| | - Themistocles L Assimes
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA
- VA Palo Alto Health Care System, Palo Alto, CA, USA
| |
Collapse
|
46
|
Di Minno A, Anesi A, Chiesa M, Cirillo F, Colombo GI, Orsini RC, Capasso F, Morisco F, Fiorelli S, Eligini S, Cavalca V, Tremoli E, Porro B, Di Minno MND. Plasma phospholipid dysregulation in patients with cystathionine-β synthase deficiency. Nutr Metab Cardiovasc Dis 2020; 30:2286-2295. [PMID: 32912785 DOI: 10.1016/j.numecd.2020.07.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/14/2020] [Accepted: 07/14/2020] [Indexed: 01/27/2023]
Abstract
BACKGROUND & AIMS Patients with cystathionine β-synthase deficiency (CBSD) exhibit high circulating levels of homocysteine and enhanced lipid peroxidation. We have characterized the plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels. METHODS AND RESULTS Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, plasma lipids were determined with an untargeted lipidomics approach in 11 CBSD patients and 11 matched healthy subjects (CTRL). Compared to CTRL, CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p < 0.02), and depletion of phosphatidylcholine (PC; p = 0.02) and of lysophosphatidylcholine (LPC; p = 0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p = 0.015) and 5.3-fold (p = 0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r = 0.520; p = 0.019) was found. CONCLUSIONS A novel biochemical abnormality in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE species is revealed by this lipidomic approach. Changes in plasma SAM and SAH concentrations are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, depletion of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with homocystinuria.
Collapse
Affiliation(s)
- Alessandro Di Minno
- Dipartimento di Farmacia, Università degli Studi di Napoli "Federico II", Napoli, Italy
| | - Andrea Anesi
- Fondazione Edmund Mach Research and Innovation Centre, Food Quality and Nutrition Department, S. Michele all' Adige, Trento, Italy
| | | | - Ferdinando Cirillo
- Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", 80131 Napoli, Italy
| | | | - Roberta C Orsini
- Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", 80131 Napoli, Italy
| | - Filomena Capasso
- Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", 80131 Napoli, Italy
| | - Filomena Morisco
- Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II", 80131 Napoli, Italy
| | | | | | | | | | | | - Matteo N D Di Minno
- Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", 80131 Napoli, Italy
| |
Collapse
|
47
|
Nia AM, Shavkunov A, Ullrich RL, Emmett MR. 137Cs γ Ray and 28Si Irradiation Induced Murine Hepatocellular Carcinoma Lipid Changes in Liver Assessed by MALDI-MSI Combined with Spatial Shrunken Centroid Clustering Algorithm: A Pilot Study. ACS OMEGA 2020; 5:25164-25174. [PMID: 33043195 PMCID: PMC7542585 DOI: 10.1021/acsomega.0c03047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 09/07/2020] [Indexed: 06/11/2023]
Abstract
Characterization of lipids by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is of great interest because not only are lipids important structural molecules in both the cell and internal organelle membranes, but they are also important signaling molecules. MALDI-MSI combined with spatial image segmentation has been previously used to identify tumor heterogeneities within tissues with distinct anatomical regions such as the brain. However, there has been no systematic study utilizing MALDI-MSI combined with spatial image segmentation to assess the tumor microenvironment in the liver. Here, we present that image segmentation can be used to evaluate the tumor microenvironment in the liver. In particular, to better understand the molecular mechanisms of irradiation-induced hepatic carcinogenesis, we used MALDI-MSI in the negative ion mode to identify lipid changes 12 months post exposure to low dose 28Si and 137Cs γ ray irradiation. We report here the changes in the lipid profiles of male C3H/HeNCrl mice liver tissues after exposure to irradiation and analyzed using the spatial shrunken centroid clustering algorithm. These findings provide valuable information as astronauts will be exposed to high-charge high-energy (HZE) particles and low-energy γ-ray irradiation during deep space travel. Even at low doses, exposure to these irradiations can lead to cancer. Previous studies infer that irradiation of mice with low-dose HZE particles induces oxidative damage and microenvironmental changes that are thought to play roles in the pathophysiology of hepatocellular carcinoma.
Collapse
Affiliation(s)
- Anna M. Nia
- Biochemistry
and Molecular Biology, The University of
Texas Medical Branch, Galveston, Texas 77555, United States
| | - Alexander Shavkunov
- Pharmacology
and Toxicology, The University of Texas
Medical Branch, Galveston, Texas 77555, United States
| | - Robert L. Ullrich
- The
Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki 732-0815, Japan
| | - Mark R. Emmett
- Biochemistry
and Molecular Biology, The University of
Texas Medical Branch, Galveston, Texas 77555, United States
- Pharmacology
and Toxicology, The University of Texas
Medical Branch, Galveston, Texas 77555, United States
- Radiation
Oncology, The University of Texas Medical
Branch, Galveston, Texas 77555, United
States
| |
Collapse
|
48
|
Bianchi F, Spitaler U, Robatscher P, Vogel RF, Schmidt S, Eisenstecken D. Comparative Lipidomics of Different Yeast Species Associated to Drosophila suzukii. Metabolites 2020; 10:E352. [PMID: 32872268 PMCID: PMC7569767 DOI: 10.3390/metabo10090352] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/25/2020] [Accepted: 08/26/2020] [Indexed: 11/16/2022] Open
Abstract
Yeasts constitute a dietary source for the spotted wing drosophila (SWD) and produce compounds that attract these flies. The study of the chemical composition of the yeast communities associated with SWD should therefore help to understand the relationship between the biology of the insect and the yeast's metabolism. In the present study, the lipidome of five yeast species isolated from grapes infested by SWD (three Hanseniaspora uvarum strains, Candida sp., Issatchenkia terricola, Metschnikowia pulcherrima and Saccharomycopsis vini) and a laboratory strain of Saccharomyces cerevisiae was explored using an untargeted approach. Additionally, the lipid profile of two species, S. cerevisiae and H. uvarum, which were reported to elicit different responses on SWD flies based on feeding and behavioral trials, was compared with a chemical enrichment approach. Overall, 171 lipids were annotated. The yeast species could be distinguished from each other based on their lipid profile, except for the three strains of H. uvarum, which were very similar to each other. The chemical enrichment analysis emphasized diversities between S. cerevisiae and H. uvarum, that could not be detected based on their global lipid profile. The information concerning differences between species in their lipidome may be of interest to future entomological studies concerning the yeast-insect interaction and could help to explain the responses of SWD to diverse yeast species.
Collapse
Affiliation(s)
- Flavia Bianchi
- Laboratory for Flavours and Metabolites, Institute for Agricultural Chemistry and Food Quality, Laimburg Research Centre, Ora (BZ), 39040 Auer, Italy; (F.B.); (P.R.)
- Chair of Technical Microbiology, School of Life Sciences Weihenstephan, Technical University of Munich, Gregor-Mendel-Straße 4, 85354 Freising, Germany;
| | - Urban Spitaler
- Entomology Group, Institute for Plant Health, Laimburg Research Centre, Ora (BZ), 39040 Auer, Italy; (U.S.); (S.S.)
- Institute of Plant Protection, Department of Crop Sciences, University of Natural Resources and Life Sciences, Gregor-Mendel-Straße 33, 1180 Vienna, Austria
| | - Peter Robatscher
- Laboratory for Flavours and Metabolites, Institute for Agricultural Chemistry and Food Quality, Laimburg Research Centre, Ora (BZ), 39040 Auer, Italy; (F.B.); (P.R.)
| | - Rudi F. Vogel
- Chair of Technical Microbiology, School of Life Sciences Weihenstephan, Technical University of Munich, Gregor-Mendel-Straße 4, 85354 Freising, Germany;
| | - Silvia Schmidt
- Entomology Group, Institute for Plant Health, Laimburg Research Centre, Ora (BZ), 39040 Auer, Italy; (U.S.); (S.S.)
| | - Daniela Eisenstecken
- Chair of Technical Microbiology, School of Life Sciences Weihenstephan, Technical University of Munich, Gregor-Mendel-Straße 4, 85354 Freising, Germany;
| |
Collapse
|
49
|
Aristizabal-Henao JJ, Jones CM, Lippa KA, Bowden JA. Nontargeted lipidomics of novel human plasma reference materials: hypertriglyceridemic, diabetic, and African-American. Anal Bioanal Chem 2020; 412:7373-7380. [PMID: 32851459 DOI: 10.1007/s00216-020-02910-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 08/05/2020] [Accepted: 08/21/2020] [Indexed: 12/20/2022]
Abstract
The unavailability of appropriate quality assurance/quality control materials in many lipidomics applications poses a significant challenge for lipidomics research. It is recommended that samples with certified values and/or consensus estimates, such as NIST SRM 1950-Metabolites in Frozen Human Plasma, be implemented in routine analyses to enable community-wide comparisons of lipidomics results and analytical workflows. Herein, we applied a nontargeted lipidomics method for the analysis of a new human plasma reference material suite developed by NIST (hypertriglyceridemic, diabetic, and African-American plasma pools), in addition to SRM 1950. We identified specific lipidomics fingerprints associated with each sample type, including lauric acid-containing lipids and elevated triacylglycerol levels in hypertriglyceridemic plasma, palmitoleic acid-containing lipids in diabetic plasma, and oxidized fatty acid-containing phospholipids in African-American plasma. This work highlights the importance of developing and profiling application-specific reference materials, while establishing reference data that may be used for system suitability and/or quality control metrics.Graphical abstract.
Collapse
Affiliation(s)
- Juan J Aristizabal-Henao
- Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, 1333 Center Drive, Gainesville, FL, 32610, USA
| | - Christina M Jones
- Chemical Sciences Division, National Institutes of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - Katrice A Lippa
- Chemical Sciences Division, National Institutes of Standards and Technology, Gaithersburg, MD, 20899, USA
| | - John A Bowden
- Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, 1333 Center Drive, Gainesville, FL, 32610, USA.
| |
Collapse
|
50
|
Cheng X, Geng F, Pan M, Wu X, Zhong Y, Wang C, Tian Z, Cheng C, Zhang R, Puduvalli V, Horbinski C, Mo X, Han X, Chakravarti A, Guo D. Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress. Cell Metab 2020; 32:229-242.e8. [PMID: 32559414 PMCID: PMC7415721 DOI: 10.1016/j.cmet.2020.06.002] [Citation(s) in RCA: 173] [Impact Index Per Article: 34.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 04/15/2020] [Accepted: 06/01/2020] [Indexed: 12/21/2022]
Abstract
Glioblastoma (GBM), a mostly lethal brain tumor, acquires large amounts of free fatty acids (FAs) to promote cell growth. But how the cancer avoids lipotoxicity is unknown. Here, we identify that GBM upregulates diacylglycerol-acyltransferase 1 (DGAT1) to store excess FAs into triglycerides and lipid droplets. Inhibiting DGAT1 disrupted lipid homeostasis and resulted in excessive FAs moving into mitochondria for oxidation, leading to the generation of high levels of reactive oxygen species (ROS), mitochondrial damage, cytochrome c release, and apoptosis. Adding N-acetyl-cysteine or inhibiting FA shuttling into mitochondria decreased ROS and cell death induced by DGAT1 inhibition. We show in xenograft models that targeting DGAT1 blocked lipid droplet formation, induced tumor cell apoptosis, and markedly suppressed GBM growth. Together, our study demonstrates that DGAT1 upregulation protects GBM from oxidative damage and maintains lipid homeostasis by facilitating storage of excess FAs. Targeting DGAT1 could be a promising therapeutic approach for GBM.
Collapse
Affiliation(s)
- Xiang Cheng
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Feng Geng
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Meixia Pan
- Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
| | - Xiaoning Wu
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Yaogang Zhong
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Chunyan Wang
- Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
| | - Zhihua Tian
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Chunming Cheng
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Rui Zhang
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Vinay Puduvalli
- Division of Neuro-Oncology, Department of Neurology, The Ohio State University, Columbus, OH 43210, USA
| | - Craig Horbinski
- Departments of Pathology and Neurosurgery, Feinberg School of Medicine at Northwestern University, Chicago, IL 60611, USA
| | - Xiaokui Mo
- Biostatistic Center and Department of Bioinformatics, College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Xianlin Han
- Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
| | - Arnab Chakravarti
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA
| | - Deliang Guo
- Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA; Center for Cancer Metabolism, James Comprehensive Cancer Center at The Ohio State University, Columbus, OH 43210, USA.
| |
Collapse
|