Unmasking the lipid landscape: carbamazepine induces alterations in Leydig cell lipidome

Unmasking the lipid landscape: carbamazepine induces alterations in Leydig cell lipidome

February 2025

Inês Nobre, Inês M. S. Guerra, Marisa Pinho, Ana D. Martins, Laura Goracci, Stefano Bonciarelli, Tânia Melo, Pedro Domingues, Artur Paiva, Pedro F. Oliveira, M. Rosário Domingues

Abstract

Leydig cells rely on lipids and fatty acids (FA) for essential functions like maintaining structural integrity, energy metabolism, and steroid hormone synthesis, including testosterone production. Carbamazepine (CBZ), a common anticonvulsant medication, can influence lipid metabolism and profiles, potentially impacting Leydig cell function and testosterone levels. Understanding this interplay is crucial to optimize treatment strategies for individuals requiring CBZ therapy while mitigating any adverse effects on male reproductive health. This study focuses on evaluating the effects of selected CBZ concentrations on the lipid homeostasis of BLTK-1 murine Leydig cells. By employing liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), we aimed to uncover the specific changes in lipid profiles induced by CBZ exposure (25 and 200 μM). FA analysis demonstrated a significant decrease in FA 22:6 n-3 with increasing CBZ concentration and an increase in the n-6/n-3 ratio. Furthermore, changes in the lipidome, particularly in lipid species belonging to phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylglycerol (PG), and sphingomyelin (SM) classes were observed. PE and PC lipid species were significantly elevated in Leydig cells exposed to 200 μM CBZ, whereas PG and SM species were downregulated. CBZ treatment significantly altered the Leydig cell phospholipidome, suggesting specific phospholipids such as PG 40:4, PG 34:1, PC O-32:1, PC 32:2, and PE P-38:6, which exhibited the lowest p-values, as potential biomarkers for clinical assessment of CBZ’s impact on Leydig cells. These findings underscore the intricate relationship between CBZ exposure and alterations in lipid profiles, offering potential insights for monitoring and mitigating the drug’s effects on male reproductive health.

Phosphatidylethanolamine species with n-3 and n-6 fatty acids modulate macrophage lipidome and attenuate responses to LPS stimulation

Phosphatidylethanolamine species with n-3 and n-6 fatty acids modulate macrophage lipidome and attenuate responses to LPS stimulation

April 2025

Tatiana Maurício, Inês M. S. Guerra, Marisa Pinho, Tânia Melo, Stefano Bonciarelli, Laura Goracci, Bruno Neves, Rosário Domingues, Pedro Domingues

Abstract

Phospholipids are increasingly recognized as key regulators of biological processes, including macrophage polarization and function. Among these, phosphatidylethanolamine (PE), a major constituent of cell membranes, is pivotal in maintaining cellular structure and function, yet the mechanisms through which native PE species influence macrophage immunometabolism remain largely unexplored. This study investigates the effects of two native PE species, PE 18:0/22:6 and PE 18:0/20:4, on the lipidome of resting and LPS-activated macrophages. Using C18 HPLC-MS/MS, we identified 337 lipid molecular species across 15 lipid subclasses, 332 of which varied significantly among conditions. Both PE 18:0/22:6 and PE 18:0/20:4 supplementation modulated the macrophage lipidome without inducing a pro-inflammatory phenotype under basal conditions. Notably, supplementation with PE 18:0/22:6 and PE 18:0/20:4 significantly increased lipid classes such as PE, PE O-, SMCLPG, LPE and PS, producing unique lipid profiles. Pre-treatment with PE 18:0/22:6 and PE 18:0/20:4 partially attenuated LPS-induced lipidomic changes, significantly reducing lipid classes like PC, including PC O- and PC P-, and Cer, which are typically linked to inflammation. While PE 18:0/20:4, from an individual lipid species perspective, may promote certain lipid profiles compatible with pro-inflammatory signaling pathways, particularly under inflammatory conditions, PE 18:0/22:6 seems to foster a lipid profile more supportive of inflammation resolution. This behaviour of PE 18:0/22:6 and PE 18:0/20:4 highlights the intricate complexity of lipid-mediated immunomodulation and emphasizes the critical role of cellular context in determining the functional outcomes of phospholipid supplementation in macrophage lipid metabolism and immune responses.

Unveiling the lipidomic profile of aerial plant and seed of the halophyte Suaeda albescens and their bioactive properties for food and nutraceutical applications

Unveiling the lipidomic profile of aerial plant and seed of the halophyte Suaeda albescens and their bioactive properties for food and nutraceutical applications

June 17, 2025

Marisa Pinho, Francisca Marques, Inês M. S. Guerra, Ana Moreira, Tânia Melo, Stefano Bonciarelli, Laura Goracci, Pedro Domingues, Ana I. Lillebø, Javier Cremades, M. Rosário Domingues

Abstract

Halophytes are gaining popularity as healthy food due to their nutritional value, as a source of essential fatty acids (FA), and various bioactive compounds. This study aimed to characterize the lipidome of the mature and green aerial parts, as well as seeds of Suaeda albescens, and evaluate the bioactivity of their lipid extracts. Plants had lower lipid content (1.29–1.45 mg/100 mg DW) than seeds (7.80 mg/100 mg DW). Triacylglycerols accounted for 70 % of seed lipids, whereas glycolipids and phospholipids constituted 70 % of plant lipids. Lipidomic analysis identified 206 lipid species belonging to different phospholipids, glycolipids and triglycerides, with large numbers of them esterified with n–6 and n–3 FA, including the most abundant FA 18:2n–6 and FA 18:3n–3. Changes in the profile of phospholipids and glycolipids distinguished the maturation stages, whereas triacyclglycerols differentiated plant from seed. Both plant and seed extracts exhibited antioxidant and anti-inflammatory properties, establishing S. albescens as a potential source of health-promoting lipids.

Lipidomic Profiling of Red Blood Cells in the Mitochondrial Fatty Acid β-oxidation Disorder MCADD Reveals Phospholipid and Sphingolipid Dysregulation

Lipidomic Profiling of Red Blood Cells in the Mitochondrial Fatty Acid β-oxidation Disorder MCADD Reveals Phospholipid and Sphingolipid Dysregulation

July 24, 2025

Inês M. S. Guerra, Helena B. Ferreira, Luísa Diogo, Sónia Moreira, Stefano Bonciarelli, Laura Goracci, Tânia Melo, Pedro Domingues, M. Rosário Domingues, Ana S. P. Moreira

Abstract

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is characterized by the accumulation of medium-chain acylcarnitines. Despite the therapeutic approach, changes in lipid homeostasis have been reported in MCADD plasma samples. Compared to plasma lipidomics, red blood cell (RBC) profiling provides a more stable biomarker that is less influenced by dietary changes and reflects long-term metabolic alterations. In this study, we assessed the plasticity of the lipidomic profile of RBC from children with MCADD and controls using C18 liquid chromatography–mass spectrometry. The results revealed significant alterations in 240 lipid species in MCADD, highlighting an upregulation of sphingolipids (sphingomyelins and ceramides) and lysophospholipid species (lysophosphatidylcholines and lysophosphatidylethanolamines) alongside a downregulation of polyunsaturated and ether-linked phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs). Also, altered PC/PE and (PC + SM)/(PE + PS) ratios could be associated with alterations in RBC membranes properties, e.g., fluidity and asymmetry. The observed changes in the lipidome suggest compromised antioxidant defenses, enhanced oxidative stress, and an inflammatory state, with potential systemic implications in MCADD lipid metabolism and long-term complications in older age. This study underscores the utility of RBC lipidomics as a robust tool for understanding the pathophysiology of MCADD. It may prove to be a useful tool for monitoring disease progression in the near future.

Rediscovering Halophyte Suaeda maritima as an Alternative crop for Food Lipids Through Aquaponic Cultivation and Lipidomics analysis

Rediscovering Halophyte Suaeda maritima as an Alternative crop for Food Lipids Through Aquaponic Cultivation and Lipidomics analysis

September 24, 2025

Marisa Pinho, Ana S. P. Moreira, Erika García Cardesín, Alexandra Pérez-González, David Gómez-Carnota, Bruna B. Neves, Stefano Bonciarelli, Laura Goracci, Tânia Melo, Pedro Domingues, Ana I. Lillebø, Javier Cremades, M. Rosário Domingues

Abstract

Halophytes are gaining recognition for their resilience and nutritional properties. Salicornia is widely consumed in Western countries. Other species like Suaeda genus have long-standing medicinal and culinary uses but remain underexplored. They can thrive in saline environments and aquaculture. Aquaponic cultivation, which can valorize aquaculture effluents and be integrated into IMTA-RAS systems, is a soil-free method that optimizes biomass and biochemical composition while reducing land and freshwater use. This study evaluated the benefits of aquaponically cultivating S. maritima, focusing on biomass yield and lipid composition. Lipidome profiling of aerial organs was conducted with LC-MS/MS and GC-MS. Biomass fresh weight increased significantly from 0.74 to 216 mg after 8-weeks of cultivation. Seventeen FA were identified, including essential FA18:2n-6 and FA18:3n-3, more abundant in aquaponic samples. Lipidomic analysis revealed 448 lipid species, including glycerophospholipids, glycolipids, acylglycerols, sphingolipids, sterol lipids, and prenol lipids. Aquaponic samples exhibited higher levels of PUFA-rich glycolipids, associated with anti-inflammatory properties, and wild samples containing more sphingolipids and acylglycerols. Glycerophospholipid profiles varied between 4- and 8-weeks. Aquaponic cultivated biomass have a more stable lipid composition than biomass collected from wild. These findings suggests aquaponic cultivation is a valuable technique for stable lipid composition, enhancing its potential as a sustainable food source.