@article{MTMT:33607647, title = {Development of a Laser Microdissection-Coupled Quantitative Shotgun Lipidomic Method to Uncover Spatial Heterogeneity}, url = {https://m2.mtmt.hu/api/publication/33607647}, author = {Varga-Zsíros, Vanda and Migh, Ede and Marton, Annamária and Kóta, Zoltán and Vizler, Csaba and Tiszlavicz, László and Horváth, Péter and Török, Zsolt and Vigh, László and Balogh, Gábor and Péter, Mária}, doi = {10.3390/cells12030428}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {33607647}, abstract = {Lipid metabolic disturbances are associated with several diseases, such as type 2 diabetes or malignancy. In the last two decades, high-performance mass spectrometry-based lipidomics has emerged as a valuable tool in various fields of biology. However, the evaluation of macroscopic tissue homogenates leaves often undiscovered the differences arising from micron-scale heterogeneity. Therefore, in this work, we developed a novel laser microdissection-coupled shotgun lipidomic platform, which combines quantitative and broad-range lipidome analysis with reasonable spatial resolution. The multistep approach involves the preparation of successive cryosections from tissue samples, cross-referencing of native and stained images, laser microdissection of regions of interest, in situ lipid extraction, and quantitative shotgun lipidomics. We used mouse liver and kidney as well as a 2D cell culture model to validate the novel workflow in terms of extraction efficiency, reproducibility, and linearity of quantification. We established that the limit of dissectible sample area corresponds to about ten cells while maintaining good lipidome coverage. We demonstrate the performance of the method in recognizing tissue heterogeneity on the example of a mouse hippocampus. By providing topological mapping of lipid metabolism, the novel platform might help to uncover region-specific lipidomic alterations in complex samples, including tumors.}, year = {2023}, eissn = {2073-4409}, orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773; Tiszlavicz, László/0000-0003-1134-6587} } @article{MTMT:33154711, title = {Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D}, url = {https://m2.mtmt.hu/api/publication/33154711}, author = {Kőszegi, Balázs and Balogh, Gábor and Berente, Zoltán and Vranesics, Anett and Pollák, Edit and Molnár, László and Takátsy, Anikó and Poór, Viktória and Wahr, Mátyás and Antus, Csenge Petra and Erős, Krisztián and Vigh, László and Gallyas, Ferenc and Péter, Mária and Veres, Balázs}, doi = {10.3390/ijms231911274}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33154711}, issn = {1661-6596}, abstract = {In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases.}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Molnár, László/0000-0002-0049-9679; Gallyas, Ferenc/0000-0002-1906-4333} } @article{MTMT:32990270, title = {Effect of HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) : protocol for a randomised controlled trial}, url = {https://m2.mtmt.hu/api/publication/32990270}, author = {Sebők, Judit and Édel, Zsófia and Dembrovszky, Fanni and Borbásné Farkas, Kornélia and Török, Zsolt and Balogh, Gábor and Péter, Mária and Papp, Ildiko and Balogi, Zsolt and Csizmadiáné Nusser, Nóra and Péter, Iván and Hooper, Philip and Geiger, Paige and Erőss, Bálint Mihály and Wittmann, István and Váncsa, Szilárd and Vigh, László and Hegyi, Péter}, doi = {10.1136/bmjopen-2022-062122}, journal-iso = {BMJ OPEN}, journal = {BMJ OPEN}, volume = {12}, unique-id = {32990270}, issn = {2044-6055}, abstract = {The burden of type 2 diabetes mellitus (T2DM) is increasing worldwide. Heat therapy has been found effective in improving glycaemic control. However, to date, there is a lack of randomised controlled studies investigating the efficacy of heat therapy in T2DM. Therefore, we aim to investigate whether heat therapy with natural thermal mineral water can improve glycaemic control in patients with T2DM.The HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) Study is a single-centre, two-arm randomised controlled trial being conducted at Harkány Thermal Rehabilitation Centre in Hungary. Patients with T2DM will be randomly assigned to group A (bath sessions in 38°C natural thermal mineral water) and group B (baths in thermoneutral water (30°C-32°C)). Both groups will complete a maximum of 5 weekly visits, averaging 50-60 visits over the 12-week study. Each session will last 30 min, with a physical check-up before the bath. At baseline, patients' T2DM status will be investigated thoroughly. Possible microvascular and macrovascular complications of T2DM will be assessed with physical and laboratory examinations. The short form-36 questionnaire will assess the quality of life. Patients will also be evaluated at weeks 4, 8 and 12. The primary endpoint will be the change of glycated haemoglobin from baseline to week 12. An estimated 65 patients will be enrolled per group, with a sample size re-estimation at the enrolment of 50% of the calculated sample size.The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (818-2/2022/EÜIG). Written informed consent is required from all participants. We will disseminate our results to the medical community and will publish our results in peer-reviewed journals.ClinicalTrials.gov, NCT05237219.}, keywords = {THERAPEUTICS; DIABETES & ENDOCRINOLOGY; general diabetes}, year = {2022}, eissn = {2044-6055}, orcid-numbers = {Dembrovszky, Fanni/0000-0001-6953-3591; Borbásné Farkas, Kornélia/0000-0002-5349-6527; Erőss, Bálint Mihály/0000-0003-3658-8427; Váncsa, Szilárd/0000-0002-9347-8163; Hegyi, Péter/0000-0003-0399-7259} } @article{MTMT:32849807, title = {Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells.}, url = {https://m2.mtmt.hu/api/publication/32849807}, author = {Tiszlavicz, Ádám and Gombos, Imre and Péter, Mária and Hegedűs, Zoltán and Hunya, Ákos and Dukic, Barbara and Nagy, István and Peksel, Begüm and Balogh, Gábor and Horváth, Ibolya and Vigh, László and Török, Zsolt}, doi = {10.3390/biomedicines10051172}, journal-iso = {BIOMEDICINES}, journal = {BIOMEDICINES}, volume = {10}, unique-id = {32849807}, abstract = {Mild stress could help cells to survive more severe environmental or pathophysiological conditions. In the current study, we investigated the cellular mechanisms which contribute to the development of stress tolerance upon a prolonged (0-12 h) fever-like (40 °C) or a moderate (42.5 °C) hyperthermia in mammalian Chinese Hamster Ovary (CHO) cells. Our results indicate that mild heat triggers a distinct, dose-dependent remodeling of the cellular lipidome followed by the expression of heat shock proteins only at higher heat dosages. A significant elevation in the relative concentration of saturated membrane lipid species and specific lysophosphatidylinositol and sphingolipid species suggests prompt membrane microdomain reorganization and an overall membrane rigidification in response to the fluidizing heat in a time-dependent manner. RNAseq experiments reveal that mild heat initiates endoplasmic reticulum stress-related signaling cascades resulting in lipid rearrangement and ultimately in an elevated resistance against membrane fluidization by benzyl alcohol. To protect cells against lethal, protein-denaturing high temperatures, the classical heat shock protein response was required. The different layers of stress response elicited by different heat dosages highlight the capability of cells to utilize multiple tools to gain resistance against or to survive lethal stress conditions.}, keywords = {MEMBRANE; STRESS; heat shock response; transcriptomics; LIPIDOMICS; Unfolded protein response; Chinese hamster ovary cells; acquired stress tolerance; membrane lipid metabolism}, year = {2022}, eissn = {2227-9059}, orcid-numbers = {Hunya, Ákos/0000-0002-4547-9284} } @article{MTMT:32666787, title = {Multifaceted Analyses of Isolated Mitochondria Establish the Anticancer Drug 2-Hydroxyoleic Acid as an Inhibitor of Substrate Oxidation and an Activator of Complex IV-Dependent State 3 Respiration}, url = {https://m2.mtmt.hu/api/publication/32666787}, author = {Mishra, K. and Péter, Mária and Nardiello, A.M. and Keller, G. and Llado, V. and Fernandez-Garcia, P. and Kahlert, U.D. and Barasch, D. and Saada, A. and Török, Zsolt and Balogh, Gábor and Escriba, P.V. and Piotto, S. and Kakhlon, O.}, doi = {10.3390/cells11030578}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {11}, unique-id = {32666787}, abstract = {The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) has been extensively investigated as a cancer therapy mainly based on its regulation of membrane lipid composition and structure, activating various cell fate pathways. We discovered, additionally, that 2OHOA can uncouple oxi-dative phosphorylation, but this has never been demonstrated mechanistically. Here, we explored the effect of 2OHOA on mitochondria isolated by ultracentrifugation from U118MG glioblastoma cells. Mitochondria were analyzed by shotgun lipidomics, molecular dynamic simulations, spectrophotometric assays for determining respiratory complex activity, mass spectrometry for assessing beta oxidation and Seahorse technology for bioenergetic profiling. We showed that the main impact of 2OHOA on mitochondrial lipids is their hydroxylation, demonstrated by simulations to decrease co-enzyme Q diffusion in the liquid disordered membranes embedding respiratory complexes. This de-creased co-enzyme Q diffusion can explain the inhibition of disjointly measured complexes I-III activ-ity. However, it doesn’t explain how 2OHOA increases complex IV and state 3 respiration in intact mitochondria. This increased respiration probably allows mitochondrial oxidative phosphorylation to maintain ATP production against the 2OHOA-mediated inhibition of glycolytic ATP production. This work correlates 2OHOA function with its modulation of mitochondrial lipid composition, reflecting both 2OHOA anticancer activity and adaptation to it by enhancement of state 3 respiration. © 2022 by the authors. Li-censee MDPI, Basel, Switzerland.}, keywords = {Mitochondria; Respiration; molecular dynamics; Glycolysis; Bioenergetics; Shotgun lipidomics; 2-Hydroxyoleic acid; Membrane Lipid Therapy}, year = {2022}, eissn = {2073-4409} } @article{MTMT:32531214, title = {Lipids and Trehalose Actively Cooperate in Heat Stress Management of Schizosaccharomyces pombe}, url = {https://m2.mtmt.hu/api/publication/32531214}, author = {Péter, Mária and Gudmann, Péter and Kóta, Zoltán and Török, Zsolt and Vigh, László and Glatz, Attila and Balogh, Gábor}, doi = {10.3390/ijms222413272}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {22}, unique-id = {32531214}, issn = {1661-6596}, year = {2021}, eissn = {1422-0067}, orcid-numbers = {Kóta, Zoltán/0000-0003-2420-8773} } @article{MTMT:31970009, title = {Male and Female Animals Respond Differently to High-Fat Diet and Regular Exercise Training in a Mouse Model of Hyperlipidemia}, url = {https://m2.mtmt.hu/api/publication/31970009}, author = {Tóth, Erzsébet Melinda and Dukay, Brigitta and Péter, Mária and Balogh, Gábor and Szűcs, Gergő and Zvara, Ágnes and Szebeni, Gábor and Hajdu, Petra and Sárközy, Márta and Puskás, László and Török, Zsolt and Csont, Tamás Bálint and Vigh, László and Sántha, Miklós}, doi = {10.3390/ijms22084198}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {22}, unique-id = {31970009}, issn = {1661-6596}, abstract = {Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We aimed to analyze the morphological, gene expression, and lipidomic patterns in the liver and adipose tissues in response to regular exercise. Healthy (wild type on a normal diet) and hyperlipidemic, high-fat diet-fed (HFD-fed) apolipoprotein B-100 (APOB-100)-overexpressing mice were trained by treadmill running for 7 months. The serum concentrations of triglyceride and tumor necrosis factor alpha (TNF alpha), as well as the level of lipid accumulation in the liver, were significantly higher in HFD-fed APOB-100 males compared to females. However, regular exercise almost completely abolished lipid accumulation in the liver of hyperlipidemic animals. The expression level of the thermogenesis marker, uncoupling protein-1 (Ucp1), was significantly higher in the subcutaneous white adipose tissue of healthy females, as well as in the brown adipose tissue of HFD-fed APOB-100 females, compared to males. Lipidomic analyses revealed that hyperlipidemia essentially remodeled the lipidome of brown adipose tissue, affecting both the membrane and storage lipid fractions, which was partially restored by exercise in both sexes. Our results revealed more severe metabolic disturbances in HFD-fed APOB-100 males compared to females. However, exercise efficiently reduced the body weight, serum triglyceride levels, expression of pro-inflammatory factors, and hepatic lipid accumulation in our model.}, year = {2021}, eissn = {1422-0067}, orcid-numbers = {Szűcs, Gergő/0000-0003-1874-2718; Szebeni, Gábor/0000-0002-6998-5632; Sárközy, Márta/0000-0002-5929-2146; Török, Zsolt/0000-0003-0836-3247; Csont, Tamás Bálint/0000-0001-5792-2768} } @article{MTMT:31647569, title = {Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome}, url = {https://m2.mtmt.hu/api/publication/31647569}, author = {Péter, Mária and Török, Wanda and Petrovics-Balog, Anna and Vigh, László and Vécsei, László and Balogh, Gábor}, doi = {10.1038/s41598-020-75502-x}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {10}, unique-id = {31647569}, issn = {2045-2322}, year = {2020}, eissn = {2045-2322}, orcid-numbers = {Vécsei, László/0000-0001-8037-3672} } @article{MTMT:31380442, title = {Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry}, url = {https://m2.mtmt.hu/api/publication/31380442}, author = {Schmidt, János and Kajtár, Béla and Juhász, Kata and Péter, Mária and Járai, Tamás and Burián, András and Kereskai, László and Gerlinger, Imre and Tornóczky, Tamás and Balogh, Gábor and Vigh, László and Márk, László and Balogi, Zsolt}, doi = {10.18632/oncotarget.27649}, journal-iso = {ONCOTARGET}, journal = {ONCOTARGET}, volume = {11}, unique-id = {31380442}, year = {2020}, eissn = {1949-2553}, pages = {2702-2717}, orcid-numbers = {Kajtár, Béla/0000-0001-5551-3709; Márk, László/0000-0002-9301-8159} } @article{MTMT:31319639, title = {Modulation of Plasma Membrane Composition and Microdomain Organization Impairs Heat Shock Protein Expression in B16-F10 Mouse Melanoma Cells}, url = {https://m2.mtmt.hu/api/publication/31319639}, author = {Crul, Tim and Csoboz, Bálint and Gombos, Imre and Marton, Annamária and Péter, Mária and Balogh, Gábor and Vizler, Csaba and Szente, Lajos and Vigh, László}, doi = {10.3390/cells9040951}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {9}, unique-id = {31319639}, year = {2020}, eissn = {2073-4409}, orcid-numbers = {Crul, Tim/0000-0002-6053-7016} }