TY - JOUR AU - Varga-Zsíros, Vanda AU - Migh, Ede AU - Marton, Annamária AU - Kóta, Zoltán AU - Vizler, Csaba AU - Tiszlavicz, László AU - Horváth, Péter AU - Török, Zsolt AU - Vigh, László AU - Balogh, Gábor AU - Péter, Mária TI - Development of a Laser Microdissection-Coupled Quantitative Shotgun Lipidomic Method to Uncover Spatial Heterogeneity JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 3 PG - 16 SN - 2073-4409 DO - 10.3390/cells12030428 UR - https://m2.mtmt.hu/api/publication/33607647 ID - 33607647 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Kőszegi, Balázs AU - Balogh, Gábor AU - Berente, Zoltán AU - Vranesics, Anett AU - Pollák, Edit AU - Molnár, László AU - Takátsy, Anikó AU - Poór, Viktória AU - Wahr, Mátyás AU - Antus, Csenge Petra AU - Erős, Krisztián AU - Vigh, László AU - Gallyas, Ferenc AU - Péter, Mária AU - Veres, Balázs TI - Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 19 PG - 16 SN - 1661-6596 DO - 10.3390/ijms231911274 UR - https://m2.mtmt.hu/api/publication/33154711 ID - 33154711 N1 - * Megosztott szerzőség AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Sebők, Judit AU - Édel, Zsófia AU - Dembrovszky, Fanni AU - Borbásné Farkas, Kornélia AU - Török, Zsolt AU - Balogh, Gábor AU - Péter, Mária AU - Papp, Ildiko AU - Balogi, Zsolt AU - Csizmadiáné Nusser, Nóra AU - Péter, Iván AU - Hooper, Philip AU - Geiger, Paige AU - Erőss, Bálint Mihály AU - Wittmann, István AU - Váncsa, Szilárd AU - Vigh, László AU - Hegyi, Péter TI - Effect of HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) : protocol for a randomised controlled trial JF - BMJ OPEN J2 - BMJ OPEN VL - 12 PY - 2022 IS - 7 PG - 7 SN - 2044-6055 DO - 10.1136/bmjopen-2022-062122 UR - https://m2.mtmt.hu/api/publication/32990270 ID - 32990270 N1 - * Megosztott szerzőség Protocol AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Tiszlavicz, Ádám AU - Gombos, Imre AU - Péter, Mária AU - Hegedűs, Zoltán AU - Hunya, Ákos AU - Dukic, Barbara AU - Nagy, István AU - Peksel, Begüm AU - Balogh, Gábor AU - Horváth, Ibolya AU - Vigh, László AU - Török, Zsolt TI - Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells. JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 5 PG - 24 SN - 2227-9059 DO - 10.3390/biomedicines10051172 UR - https://m2.mtmt.hu/api/publication/32849807 ID - 32849807 N1 - Funding Agency and Grant Number: Hungarian Basic Research Fund [OTKA ANN 132280]; Eotvos Lorand Research Network Funding text: This research was funded by the Hungarian Basic Research Fund (OTKA ANN 132280) and Eotvos Lorand Research Network. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Mishra, K. AU - Péter, Mária AU - Nardiello, A.M. AU - Keller, G. AU - Llado, V. AU - Fernandez-Garcia, P. AU - Kahlert, U.D. AU - Barasch, D. AU - Saada, A. AU - Török, Zsolt AU - Balogh, Gábor AU - Escriba, P.V. AU - Piotto, S. AU - Kakhlon, O. TI - 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 JF - CELLS J2 - CELLS-BASEL VL - 11 PY - 2022 IS - 3 SN - 2073-4409 DO - 10.3390/cells11030578 UR - https://m2.mtmt.hu/api/publication/32666787 ID - 32666787 N1 - Department of Neurology, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, 91120, Israel Faculty of Medicine, Hebrew University of Jerusalem, Ein Kerem, Jerusalem, 9112102, Israel Lipodom Ltd., Dorottya utca 35-37, Szeged, 6726, Hungary Biological Research Centre, Institute of Biochemistry, Szeged, 6726, Hungary Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, SA, Fisciano, 84084, Italy Bionam Center for Biomaterials, University of Salerno, Via Giovanni Paolo II, 132, SA, Fisciano, 84084, Italy Department of Genetics, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, 9112102, Israel Laminar Pharmaceuticals, Ctra. de Valldemossa Km. 7, 4 Parc BIT Ed. Naorte Bolque A-1°-3, Palma de Mallorca, 07121, Spain Molecular and Experimental Surgery, Clinic for General, Visceral, Vascular, and Transplant Surgery, Medical Faculty, University Hospital Magdeburg, Magdeburg, 39120, Germany Mass Spectrometry Unit, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel Department of Biology, University of the Balearic Islands, Palma de Mallorca, 07122, Spain Export Date: 11 February 2022 Correspondence Address: Escriba, P.V.; Laminar Pharmaceuticals, Ctra. de Valldemossa Km. 7, 4 Parc BIT Ed. Naorte Bolque A-1°-3, Spain; email: pablo.escriba@uib.es Correspondence Address: Piotto, S.; Department of Pharmacy, Via Giovanni Paolo II, 132, SA, Italy; email: piotto@unisa.it Correspondence Address: Kakhlon, O.; Department of Neurology, Ein Kerem, Israel; email: ork@hadassah.org.il AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Péter, Mária AU - Gudmann, Péter AU - Kóta, Zoltán AU - Török, Zsolt AU - Vigh, László AU - Glatz, Attila AU - Balogh, Gábor TI - Lipids and Trehalose Actively Cooperate in Heat Stress Management of Schizosaccharomyces pombe JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 24 SN - 1661-6596 DO - 10.3390/ijms222413272 UR - https://m2.mtmt.hu/api/publication/32531214 ID - 32531214 N1 - Cited By :3 Export Date: 20 September 2022 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Erzsébet Melinda AU - Dukay, Brigitta AU - Péter, Mária AU - Balogh, Gábor AU - Szűcs, Gergő AU - Zvara, Ágnes AU - Szebeni, Gábor AU - Hajdu, Petra AU - Sárközy, Márta AU - Puskás, László AU - Török, Zsolt AU - Csont, Tamás Bálint AU - Vigh, László AU - Sántha, Miklós TI - Male and Female Animals Respond Differently to High-Fat Diet and Regular Exercise Training in a Mouse Model of Hyperlipidemia JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 8 PG - 22 SN - 1661-6596 DO - 10.3390/ijms22084198 UR - https://m2.mtmt.hu/api/publication/31970009 ID - 31970009 N1 - Institute of Biochemistry, ELKH Biological Research Centre, Szeged, H-6726, Hungary Doctoral School in Biology, University of Szeged, Szeged, H-6726, Hungary MEDICS Research Group, Department of Biochemistry, Interdisciplinary Center of Excellence, University of Szeged, Szeged, H-6720, Hungary Laboratory of Functional Genomics, ELKH Biological Research Centre, Szeged, H-6726, Hungary Export Date: 14 May 2021 Correspondence Address: Tóth, M.E.; Institute of Biochemistry, Hungary; email: toth.erzsebetmelinda@brc.hu Institute of Biochemistry, ELKH Biological Research Centre, Szeged, H-6726, Hungary Doctoral School in Biology, University of Szeged, Szeged, H-6726, Hungary MEDICS Research Group, Department of Biochemistry, Interdisciplinary Center of Excellence, University of Szeged, Szeged, H-6720, Hungary Laboratory of Functional Genomics, ELKH Biological Research Centre, Szeged, H-6726, Hungary Export Date: 22 May 2021 Correspondence Address: Tóth, M.E.; Institute of Biochemistry, Hungary; email: toth.erzsebetmelinda@brc.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Péter, Mária AU - Török, Wanda AU - Petrovics-Balog, Anna AU - Vigh, László AU - Vécsei, László AU - Balogh, Gábor TI - Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain–Barré syndrome JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 10 PY - 2020 IS - 1 PG - 13 SN - 2045-2322 DO - 10.1038/s41598-020-75502-x UR - https://m2.mtmt.hu/api/publication/31647569 ID - 31647569 LA - English DB - MTMT ER - TY - JOUR AU - Schmidt, János AU - Kajtár, Béla AU - Juhász, Kata AU - Péter, Mária AU - Járai, Tamás AU - Burián, András AU - Kereskai, László AU - Gerlinger, Imre AU - Tornóczky, Tamás AU - Balogh, Gábor AU - Vigh, László AU - Márk, László AU - Balogi, Zsolt TI - Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry JF - ONCOTARGET J2 - ONCOTARGET VL - 11 PY - 2020 IS - 28 SP - 2702 EP - 2717 PG - 16 SN - 1949-2553 DO - 10.18632/oncotarget.27649 UR - https://m2.mtmt.hu/api/publication/31380442 ID - 31380442 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Crul, Tim AU - Csoboz, Bálint AU - Gombos, Imre AU - Marton, Annamária AU - Péter, Mária AU - Balogh, Gábor AU - Vizler, Csaba AU - Szente, Lajos AU - Vigh, László TI - Modulation of Plasma Membrane Composition and Microdomain Organization Impairs Heat Shock Protein Expression in B16-F10 Mouse Melanoma Cells JF - CELLS J2 - CELLS-BASEL VL - 9 PY - 2020 IS - 4 PG - 14 SN - 2073-4409 DO - 10.3390/cells9040951 UR - https://m2.mtmt.hu/api/publication/31319639 ID - 31319639 LA - English DB - MTMT ER -