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Keywords = lipid class ratio

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12 pages, 481 KB  
Article
The Impact of Glucagon-like Peptide-1 Receptor Agonists on Cardiovascular–Kidney–Metabolic Health in Romanian Patients with Type 2 Diabetes: A Retrospective Study
by Niculina Lixandru, Laura Gaita, Simona Popescu, Andreea Herascu, Bogdan Timar and Romulus Timar
J. Clin. Med. 2026, 15(1), 152; https://doi.org/10.3390/jcm15010152 - 25 Dec 2025
Viewed by 417
Abstract
Background/objectives: Chronic degenerative complications of diabetes, such as atherosclerotic cardiovascular disease and chronic kidney disease, contribute to an increased morbimortality in patients with type 2 diabetes (T2D), and thus, a multifactorial approach becomes essential. Among the classes of antihyperglycemic agents with beneficial pleiotropic [...] Read more.
Background/objectives: Chronic degenerative complications of diabetes, such as atherosclerotic cardiovascular disease and chronic kidney disease, contribute to an increased morbimortality in patients with type 2 diabetes (T2D), and thus, a multifactorial approach becomes essential. Among the classes of antihyperglycemic agents with beneficial pleiotropic cardiorenal effects, the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven to reduce the risk of major adverse cardiovascular (CV) and renal events. This study aims to assess the impact of treatment with GLP-1 RA on CV risk factors, insulin sensitivity, and renal function in Romanian patients with T2D. Methods: In an observational retrospective study, 150 patients with T2D were evaluated at the start of therapy with a GLP-1 RA and then after 6 and 12 months. Results: After 12 months of treatment, 59.3% of patients succeeded in achieving weight loss of over 5% of their initial weight, and 24.7% of patients achieved weight loss of over 10% of their initial weight, with the most significant decrease being measured in the first 6 months. HbA1c has shown a similar profile, with a significant reduction in the first 6 months of treatment, continued at a slower rate in the following 6 months. Additionally, the lipid profile, blood pressure values, and uric acid values, alongside the triglyceride/high-density lipoprotein cholesterol (TG/HDLc) ratio and the triglyceride–glucose (TyG) index have improved in these T2D patients treated with GLP-1 RA, while their eGFR decrease was slower than the one expected for similar populations without such a pharmacologic agent in their regimen. Conclusions: Treatment with GLP-1 RA in patients with T2D is associated with an improved cardiovascular–kidney–metabolic risk profile, ameliorated glycemic control, reduced weight, lower insulin resistance, and slower kidney disease progression. Full article
(This article belongs to the Special Issue Clinical Advances in Diabetes, Obesity, and Hypertension)
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29 pages, 2351 KB  
Article
Omega-3 Source Matters: Comparative Lipid Signatures and Quantitative Distribution of EPA/DHA Across Marine Resources
by Kolos Makay, Carola Griehl, Stephan Schilling and Claudia Grewe
Mar. Drugs 2026, 24(1), 4; https://doi.org/10.3390/md24010004 - 20 Dec 2025
Viewed by 1471
Abstract
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential omega-3 polyunsaturated fatty acids (n-3 PUFAs) with well-established health benefits. They occur primarily in marine resources, while their quantitative distribution within the glycerolipidome is rarely analyzed. Therefore, we investigated major commercial sources, including 12 [...] Read more.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential omega-3 polyunsaturated fatty acids (n-3 PUFAs) with well-established health benefits. They occur primarily in marine resources, while their quantitative distribution within the glycerolipidome is rarely analyzed. Therefore, we investigated major commercial sources, including 12 microalgal species, the protist Schizochytrium sp., four fish species, and nine commercial n-3 supplements (fish, krill and Schizochytrium-derived “algal” oils) by high-performance thin-layer chromatography–gas chromatography–mass spectrometry (HPTLC–GC–MS). The class-resolved mapping of EPA and DHA revealed signature lipid profiles across all sources. In microalgae, 60–80% of EPA was localized in glycolipids, whereas in Schizochytrium and fish, >90% of DHA occurred in triacylglycerols. Krill oils exhibited phospholipid-rich profiles with ~70% of phosphatidylcholine-bound DHA. Nutritional indices also highlighted major differences: fish and fish oils showed favorable PUFA-to-saturated FA ratios (>0.45) and hypocholesterolemic-to-hypercholesterolemic ratios (>1), while Schizochytrium-based “algal” oils even surpassed these values. The microalgae Nannochloropsis granulata contained the highest EPA content in biomass form, combined with favorable nutritional indices. Beyond total n-3 content in relation to recommended daily intake values, the lipid-class distribution and nutritional indices should be considered decisive metrics for evaluating the health relevance of n-3 resources in the human diet. Full article
(This article belongs to the Special Issue Applications of Lipids from Marine Sources)
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20 pages, 2742 KB  
Article
Untargeted Metabolomics Reveals Distinct Soil Metabolic Profiles Across Land Management Practices
by Zane A. Vickery, Hector F. Castro, Stephen P. Dearth, Eric D. Tague, Aimée T. Classen, Jessica A. Moore, Michael S. Strickland and Shawn R. Campagna
Metabolites 2025, 15(12), 783; https://doi.org/10.3390/metabo15120783 - 4 Dec 2025
Viewed by 619
Abstract
Background/Objectives: Land management practices strongly influence soil biochemical processes, yet conventional soil measurements often overlook dynamic small-molecule variation underlying nutrient cycling and microbial activity. This study aimed to evaluate whether MS1-based untargeted metabolomics can resolve meaningful biochemical differences among soil systems [...] Read more.
Background/Objectives: Land management practices strongly influence soil biochemical processes, yet conventional soil measurements often overlook dynamic small-molecule variation underlying nutrient cycling and microbial activity. This study aimed to evaluate whether MS1-based untargeted metabolomics can resolve meaningful biochemical differences among soil systems under distinct land management practices. Methods: Soils from six land-use types—conventional cultivation, organic cultivation, pasture, white pine, tulip poplar, and hardwood forest—were analyzed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Multivariate analyses, including PLS-DA, were performed to evaluate metabolic variation across systems. Both identified metabolites and unknown spectral features (MSI Level 4) were assessed, and biosynthetic class assignment of unknown features was performed using NPClassifier. Results: Metabolic features revealed clear separation between land management systems, demonstrating distinct chemical fingerprints across ecosystems. While conventional elemental ratios (e.g., C/N) showed minimal differentiation, phosphorus-related stoichiometric ratios (C/P and N/P) displayed strong land-use-dependent differences. NPClassifier superclasses highlighted unique chemical patterns, with forest soils enriched in diverse secondary metabolites, cultivated soils characterized by simplified profiles, and pasture soils dominated by microbial membrane lipids and alkaloids. Conclusions: Untargeted MS1-based metabolomics effectively distinguished soil systems under different land-use practices and revealed ecologically meaningful variation even without complete structural identification. This study demonstrates that an MS1-only workflow leveraging unknown spectral features can robustly distinguish soil systems, underscoring their value in untargeted metabolomics analyses. Full article
(This article belongs to the Section Environmental Metabolomics)
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26 pages, 5836 KB  
Article
Integrative Study of the Life Cycle in the Marine Protist Thraustochytrium aureum ssp. strugatskii
by Alexey V. Doroshkov, Ludmila G. Naumenko, Daniil A. Iukhtanov, Ksenia N. Morozova, Elena V. Kiseleva, Aleksei G. Menzorov and Ulyana S. Zubairova
Int. J. Mol. Sci. 2025, 26(23), 11302; https://doi.org/10.3390/ijms262311302 - 22 Nov 2025
Viewed by 405
Abstract
Thraustochytrium aureum ssp. strugatskii, a marine protist belonging to the class Labyrinthulea, exhibits a complex life cycle characterized by alternating motile and vegetative phases. Using an integrative multimodal microscopy approach, we reconstructed its full developmental cycle and analyzed the coordination between cellular [...] Read more.
Thraustochytrium aureum ssp. strugatskii, a marine protist belonging to the class Labyrinthulea, exhibits a complex life cycle characterized by alternating motile and vegetative phases. Using an integrative multimodal microscopy approach, we reconstructed its full developmental cycle and analyzed the coordination between cellular morphology, subcellular architecture, and population-level behavior. Transmission and scanning electron microscopy, combined with fluorescence and time-lapse imaging, revealed the dynamics of nuclear division, organelle rearrangement, and zoospore formation. Morphometric analysis of serial ultrathin sections demonstrated distinct changes in mitochondrial distribution, Golgi apparatus, and lipid droplet abundance during transitions between stages. We have shown that vegetative cells undergo synchronized karyokinesis coupled with stable nuclear-to-cytoplasmic ratios, leading to the emergence of multinucleate stages prior to zoospore formation. The integration of ultrastructural and dynamic data enabled us to propose a systems-level model linking metabolic state, morphogenesis, and population structure. This model highlights feedback regulation between nutrient availability, biomass accumulation, and developmental synchronization. Our results establish that T. aureum ssp. strugatskii has good potential to serve as a tractable model organism for systems-level studies of protists and provide an initial framework for predictive modeling of its life cycle under controlled conditions. Full article
(This article belongs to the Special Issue Marine Fungi: From Molecular Biology to Biotechnology Application)
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32 pages, 12229 KB  
Article
Shared Plasma Metabolites Mediate Causal Effects of Metabolic Diseases on Colorectal Cancer: A Two-Step Mendelian Randomization Study
by Xinyi Shi, Yuxin Tang, Yu Zhang, Yu Cheng, Yingying Ma, Fangrong Yan and Tiantian Liu
Biomedicines 2025, 13(10), 2433; https://doi.org/10.3390/biomedicines13102433 - 6 Oct 2025
Viewed by 1285
Abstract
Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify [...] Read more.
Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify the plasma metabolites mediating these effects; and (3) explore downstream regulatory genes and druggable targets. Methods: Using linkage disequilibrium score regression and two-sample Mendelian randomization, we assessed the causal relationships between each metabolic trait and CRC. A total of 1091 plasma metabolites and 309 metabolite ratios were identified and analyzed for mediating effects by a two-step MR approach. Colocalization analyses evaluated shared genetic loci. The findings were validated in the UK Biobank for metabolite-trait associations. The expression of candidate genes was explored using data from TCGA, GTEx, and GEO. A FADS1-centered protein–protein interaction (PPI) network was constructed via STRING. Results: BMI, waist circumference, basal metabolic rate, insulin resistance and metabolic syndrome exhibited both genetic correlation and causal effects on CRC. Five plasma metabolites—mannonate, the glucose/mannose ratio, plasma free asparagine, 1-linolenoyl-2-linolenoyl-GPC (18:2/18:3), and the mannose/trans-4-hydroxyproline ratio—were identified as shared central mediators. A colocalization analysis showed rs174546 linked CRC and 1-linolenoyl-2-linoleoyl-GPC. Validation in the UK Biobank confirmed the associations between phosphatidylcholine (the lipid class of this metabolite), adiposity measures, and CRC risk. An integrative analysis of TCGA, GTEx, and GEO revealed consistent upregulation of FADS1/2/3 and FEN1 in CRC, with high FADS1 expression predicting a poorer prognosis and showing the distinct cell-type expression in adipose and colon tissue. The PPI network mapping uncovered nine FADS1 interacting proteins targeted by supplements such as α-linolenic acid and eicosapentaenoic acid. Conclusions: This study systematically reveals, for the first time, the shared intermediary plasma metabolites and their regulatory genes in the causal pathway from metabolic diseases to CRC. These findings provide candidate targets for subsequent functional validation and biomarker development. Full article
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15 pages, 643 KB  
Article
Determinants of Atherogenic Dyslipidemia and Lipid Ratios: Associations with Sociodemographic Profile, Lifestyle, and Social Isolation in Spanish Workers
by Pere Riutord-Sbert, Pedro Juan Tárraga López, Ángel Arturo López-González, Irene Coll Campayo, Carla Busquets-Cortés and José Ignacio Ramírez Manent
J. Clin. Med. 2025, 14(19), 7039; https://doi.org/10.3390/jcm14197039 - 5 Oct 2025
Viewed by 1166
Abstract
Background: Atherogenic dyslipidemia is defined by the coexistence of high triglyceride concentrations, low levels of high-density lipoprotein cholesterol (HDL-C), and an excess of small, dense particles of low-density lipoprotein cholesterol (LDL-C). This lipid profile is strongly associated with an increased burden of cardiovascular [...] Read more.
Background: Atherogenic dyslipidemia is defined by the coexistence of high triglyceride concentrations, low levels of high-density lipoprotein cholesterol (HDL-C), and an excess of small, dense particles of low-density lipoprotein cholesterol (LDL-C). This lipid profile is strongly associated with an increased burden of cardiovascular disease and represents a leading cause of global morbidity and mortality. To better capture this risk, composite lipid ratios—including total cholesterol to HDL-C (TC/HDL-C), LDL-C to HDL-C (LDL-C/HDL-C), triglycerides to HDL-C (TG/HDL-C), and the atherogenic dyslipidemia index (AD)—have emerged as robust markers of cardiometabolic health, frequently demonstrating superior predictive capacity compared with isolated lipid measures. Despite extensive evidence linking these ratios to cardiovascular disease, few large-scale studies have examined their association with sociodemographic characteristics, lifestyle behaviors, and social isolation in working populations. Methods: We conducted a cross-sectional analysis of a large occupational cohort of Spanish workers evaluated between January 2021 and December 2024. Anthropometric, biochemical, and sociodemographic data were collected through standardized clinical protocols. Indices of atherogenic risk—namely the ratios TC/HDL-C, LDL-C/HDL-C, TG/HDL-C, and the atherogenic dyslipidemia index (AD)—were derived from fasting lipid measurements. The assessment of lifestyle factors included tobacco use, physical activity evaluated through the International Physical Activity Questionnaire (IPAQ), adherence to the Mediterranean dietary pattern using the MEDAS questionnaire, and perceived social isolation measured by the Lubben Social Network Scale. Socioeconomic classification was established following the criteria proposed by the Spanish Society of Epidemiology. Logistic regression models were fitted to identify factors independently associated with moderate-to-high risk for each lipid indicator, adjusting for potential confounders. Results: A total of 117,298 workers (71,384 men and 45,914 women) were included. Men showed significantly higher odds of elevated TG/HDL-C (OR 4.22, 95% CI 3.70–4.75) and AD (OR 2.95, 95% CI 2.70–3.21) compared with women, whereas LDL-C/HDL-C ratios were lower (OR 0.86, 95% CI 0.83–0.89). Advancing age was positively associated with all lipid ratios, with the highest risk observed in participants aged 60–69 years. Lower social class, smoking, physical inactivity, poor adherence to the Mediterranean diet, and low social isolation scores were consistently linked to higher atherogenic risk. Physical inactivity showed the strongest associations across all indicators, with ORs ranging from 3.54 for TC/HDL-C to 7.12 for AD. Conclusions: Atherogenic dyslipidemia and elevated lipid ratios are strongly associated with male sex, older age, lower socioeconomic status, unhealthy lifestyle behaviors, and reduced social integration among Spanish workers. These findings highlight the importance of workplace-based cardiovascular risk screening and targeted prevention strategies, particularly in high-risk subgroups. Interventions to promote physical activity, healthy dietary patterns, and social connectedness may contribute to lowering atherogenic risk in occupational settings. Full article
(This article belongs to the Section Cardiovascular Medicine)
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16 pages, 1872 KB  
Article
Sociodemographic, Lifestyle, and Quality of Life Determinants of Atherogenic Risk: A Cross-Sectional Study in a Large Cohort of Spanish Workers
by María Dolores Marzoa Jansana, Pedro Juan Tárraga López, Juan José Guarro Miquel, Ángel Arturo López-González, Pere Riutord Sbert, Carla Busquets-Cortés and José Ignacio Ramírez-Manent
J. Clin. Med. 2025, 14(19), 6876; https://doi.org/10.3390/jcm14196876 - 28 Sep 2025
Viewed by 631
Abstract
Background: Atherosclerosis is a leading cause of cardiovascular morbidity and mortality worldwide. Although lipid-derived atherogenic indices are widely used for cardiovascular risk assessment, their relationship with sociodemographic factors, lifestyle behaviors, and health-related quality of life (HRQoL) in occupational populations remains insufficiently explored. This [...] Read more.
Background: Atherosclerosis is a leading cause of cardiovascular morbidity and mortality worldwide. Although lipid-derived atherogenic indices are widely used for cardiovascular risk assessment, their relationship with sociodemographic factors, lifestyle behaviors, and health-related quality of life (HRQoL) in occupational populations remains insufficiently explored. This study aimed to evaluate the association between atherogenic risk, measured by total cholesterol/high-density lipoprotein cholesterol (TC/HDL-c), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-c/HDL-c), triglyceride/high-density lipoprotein cholesterol (TG/HDL-c), and atherogenic dyslipidemia (AD) and sociodemographic, lifestyle, and HRQoL variables in a large cohort of Spanish workers. Methods: We conducted a cross-sectional analysis of 100,014 Spanish workers aged 18–69 years, of whom 39.9% were women, with a mean age of 38.2 years (SD 10.2 or IQR) and 38.9 years (SD 10.3 or IQR) for men, during the health examinations carried out between 2021 and 2024. Sociodemographic variables included sex, age group, and occupational social class. Lifestyle factors comprised smoking status, adherence to the Mediterranean diet (MEDAS score), and physical activity (IPAQ categories). HRQoL was assessed using the 12-item Short Form Survey (SF-12), stratified into good vs. poor categories. Logistic regression models were applied to estimate odds ratios (OR) and 95% confidence intervals (CI) for moderate-to-high atherogenic risk across indices, adjusting for potential confounders. Results: Men exhibited a lower likelihood of moderate-to-high TC/HDL-c and LDL-c/HDL-c but a markedly higher probability of elevated TG/HDL-c and AD compared to women (OR range: 0.42–3.67, p < 0.001). A clear age-related gradient was observed across all indices, with participants aged 60–69 showing the highest risk (OR range: 2.28–7.84, p < 0.001). Lower social class, smoking, physical inactivity, poor diet, and poor SF-12 scores were significantly associated with increased atherogenic risk, with physical inactivity (OR up to 8.61) and poor diet (OR up to 4.98) emerging as the strongest predictors. Conclusions: Atherogenic risk in this large working cohort is strongly influenced by both traditional cardiovascular risk factors and HRQoL. Integrating lifestyle modification and quality-of-life improvement strategies into workplace health programs could substantially reduce the atherogenic burden. Longitudinal research is needed to confirm these associations and guide targeted interventions. Full article
(This article belongs to the Section Cardiovascular Medicine)
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30 pages, 500 KB  
Systematic Review
Role of Lipidomics in Respiratory Tract Infections: A Systematic Review of Emerging Evidence
by Vasiliki E. Georgakopoulou, Konstantinos Dodos and Vassiliki C. Pitiriga
Microorganisms 2025, 13(9), 2190; https://doi.org/10.3390/microorganisms13092190 - 19 Sep 2025
Cited by 1 | Viewed by 1719
Abstract
Lower respiratory tract infections (LRTIs) remain a major cause of global morbidity and mortality, yet accurate pathogen identification and risk stratification continue to pose clinical challenges. Lipidomics—the comprehensive analysis of lipid species within biological systems—has emerged as a promising tool to unravel host–pathogen [...] Read more.
Lower respiratory tract infections (LRTIs) remain a major cause of global morbidity and mortality, yet accurate pathogen identification and risk stratification continue to pose clinical challenges. Lipidomics—the comprehensive analysis of lipid species within biological systems—has emerged as a promising tool to unravel host–pathogen interactions and reveal novel diagnostic and prognostic biomarkers. This systematic review synthesizes evidence from nine original studies applying mass spectrometry-based lipidomic profiling in human LRTIs, including community-acquired pneumonia (CAP), ventilator-associated pneumonia (VAP), and coronavirus disease 2019 (COVID-19). Across diverse study designs, sample types, and analytical platforms, consistent alterations in lipid metabolism were observed. Perturbations in phospholipid classes, particularly phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs), were frequently associated with disease severity and immune activation. The ratios of PC to LPC and phosphatidylethanolamine (PE) to lysophosphatidylethanolamine (LPE) emerged as markers of inflammatory remodeling. Sphingolipids—including sphingomyelins (SMs) and sphingosine-1-phosphate (S1P)—were identified as key modulators of monocyte and neutrophil activation. Fatty acid–derived lipid mediators such as oxylipins (e.g., 12,13-epoxyoctadecenoic acid and 15-hydroxyeicosatetraenoic acid) and acylcarnitines reflected pathogen-specific immune responses and mitochondrial dysfunction. Several lipid-based classifiers demonstrated superior diagnostic and prognostic performance compared to conventional clinical scores, including the CURB-65 and pneumonia severity index. However, significant heterogeneity in experimental design, lipid identification workflows, and reporting standards limits inter-study comparability. While preliminary findings support the integration of lipidomics into infectious disease research, larger multi-omic and longitudinal studies are required. This review provides the first comprehensive synthesis of lipidomic alterations in human LRTIs and highlights their emerging translational relevance. Full article
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14 pages, 1620 KB  
Article
Lipid Composition Analysis of Cricket Oil from Crickets Fed with Broken Rice-Derived Bran
by Ryosuke Sogame, Taiki Miyazawa, Masako Toda, Akihiro Iijima, Maharshi Bhaswant and Teruo Miyazawa
Insects 2025, 16(9), 951; https://doi.org/10.3390/insects16090951 - 11 Sep 2025
Cited by 2 | Viewed by 1039
Abstract
This study investigated the effect of rice bran derived from broken rice feeding on the lipid classes and fatty acid composition of oil extracted from crickets (Acheta domesticus). During the final seven days prior to cricket oil extraction, crickets were fed [...] Read more.
This study investigated the effect of rice bran derived from broken rice feeding on the lipid classes and fatty acid composition of oil extracted from crickets (Acheta domesticus). During the final seven days prior to cricket oil extraction, crickets were fed either rice bran or control feed. The lipid classes in both the cricket oil and feed materials (rice bran or control feed) were identified using thin-layer chromatography, while the proportion of neutral lipids, phospholipids, and glycolipids was quantified by solid-phase extraction. Fatty acid composition was determined using GC-FID. Cricket oil from the rice bran-fed group exhibited a significantly higher ratio of glycolipids, which are abundant in rice bran, compared to the control group. Although both oleic and linoleic acid levels were significantly higher than in the control feed, only the oleic acid proportion was significantly increased in the cricket oil from the rice bran-fed group. Additionally, the ω-6/ω-3 ratio in each lipid fraction was significantly higher in the rice bran-fed group compared to the control group. These results suggest that dietary supplementation with rice bran derived from broken rice significantly alters the lipid profile of crickets and may represent a valuable strategy for enhancing the nutritional quality of cricket oil. Full article
(This article belongs to the Section Role of Insects in Human Society)
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15 pages, 838 KB  
Article
Predictive Utility and Metabolomic Signatures of TG/HDL-C Ratio for Metabolic Syndrome Without Cardiovascular Disease and/or Diabetes in Qatari Adults
by Noora Kano, Najeha Anwardeen, Khaled Naja, Asma A. Elashi, Ahmed Malki and Mohamed A. Elrayess
Metabolites 2025, 15(9), 574; https://doi.org/10.3390/metabo15090574 - 28 Aug 2025
Viewed by 1403
Abstract
Background: Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), especially in Middle Eastern populations with a high metabolic burden. This study aimed to evaluate the predictive utility of different lipid ratios, including triglyceride-to-high-density [...] Read more.
Background: Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), especially in Middle Eastern populations with a high metabolic burden. This study aimed to evaluate the predictive utility of different lipid ratios, including triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein (LDL-C)/HDL-C, and non-HDL-C/HDL-C, for identifying MetS. In addition, we aimed to characterise the underlying metabolic dysregulation using the most predictive lipid ratio by comparing metabolomic profiles between high-risk (T3) and low-risk (T1) groups. Method: We conducted a cross-sectional study using data from 2179 Qatari adults without CVD and/or T2DM. The predictive value of each lipid ratio for MetS was compared. Untargeted metabolomics was performed to profile metabolic changes between T3 and T1. Results: After adjustment for age, sex, and BMI, TG/HDL-C showed the highest discriminative ability for MetS (AUC = 0.896, 95% CI: 0.88–0.91; OR = 4.36, 95% CI: 3.63–5.28, p < 0.0001). In pairwise AUC comparisons, TG/HDL-C outperformed LDL-C/HDL-C (p = 2.6 × 10−4, after correction for multiple comparisons), with no significant differences versus other ratios. The high-risk group exhibited raised levels of phosphatidylethanolamines, phosphatidylinositols, and diacylglycerols, and lower levels of sphingomyelins and plasmalogens. These lipid classes have been suggested to be implicated in insulin resistance and metabolic dysfunction. Elevated monoacylglycerols were identified in high-TG/HDL-C groups, representing a previously underreported pattern. Conclusions: The TG/HDL-C ratio showed a better association with MetS compared with other lipid ratios and was linked to distinct metabolomic signatures. These findings suggest potential value for early risk evaluation, but longitudinal and mechanistic studies are needed to confirm clinical applicability. Full article
(This article belongs to the Special Issue Current Research in Metabolic Syndrome and Cardiometabolic Disorders)
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15 pages, 3716 KB  
Article
Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals
by Akiko Hanyuda, Oana A. Zeleznik, Yoshihiko Raita, Danielle E. Haslam, Qi Sun, Kazuno Negishi, Louis R. Pasquale, Jessica Lasky-Su, Janey L. Wiggs and Jae H. Kang
Metabolites 2025, 15(7), 469; https://doi.org/10.3390/metabo15070469 - 9 Jul 2025
Viewed by 1329
Abstract
Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS). Methods: We identified [...] Read more.
Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS). Methods: We identified 217 XFG cases and 217 matched controls nested within three prospective health professional cohorts with plasma collected a mean 11.8 years before case identification. Plasma metabolites were analyzed using the targeted NMR Nightingale platform. Conditional logistic models and Metabolite Set Enrichment Analysis were performed. Multiple comparison issues were addressed using the number of effective tests (NEF) and false discovery rate (FDR). Results: Among 235 profiled metabolites, higher glucose was significantly associated with a lower risk of XFG (odds ratio (95%CI) = 0.42 (0.26, 0.7); NEF = 0.03). Among metabolite classes, lipoprotein subclasses and branched-chain amino acids were inversely associated, while relative lipoprotein lipid concentrations were adversely associated (FDR < 0.05). Conclusion: NMR profiling revealed that glucose, branched-chain amino acids, lipoprotein subclasses, and relative lipoprotein lipid concentrations may play important roles in XFG etiology. Full article
(This article belongs to the Special Issue Metabolomics of the Eye and Adnexa)
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25 pages, 3592 KB  
Article
Flavonoid Glycosides and Phenolic Acids from Inula Oculus-Christi Modulate Membrane Organization and Provide Antioxidant Protection
by Ralitsa Veleva, Tanya Topouzova-Hristova, Aneliya Kostadinova, Dayana Benkova, Antoaneta Trendafilova, Viktoria Ivanova, Veselina Moskova-Doumanova, Kirilka Mladenova, Jordan Doumanov, Vesela Yordanova and Galya Staneva
Molecules 2025, 30(13), 2740; https://doi.org/10.3390/molecules30132740 - 25 Jun 2025
Cited by 1 | Viewed by 1601
Abstract
Oxidative stress induces lipid peroxidation within the membrane bilayer, thereby compromising membrane integrity. Polyphenols (PPs), renowned for their antioxidant properties, have been shown to mitigate oxidative damage. Here, we investigated the structural and antioxidant effects of PPs—specifically flavonoid glycosides (FGs) and phenolic acids [...] Read more.
Oxidative stress induces lipid peroxidation within the membrane bilayer, thereby compromising membrane integrity. Polyphenols (PPs), renowned for their antioxidant properties, have been shown to mitigate oxidative damage. Here, we investigated the structural and antioxidant effects of PPs—specifically flavonoid glycosides (FGs) and phenolic acids (PAs)—extracted from Inula oculus-christi using steady-state fluorescence spectroscopy in both model and cell membranes. Membrane lipid order was evaluated using DPH and Laurdan spectroscopy, while DPH-TEMPO fluorescence quenching was employed to quantify raft-like domain formation in model systems. The antioxidant capacity of the PP extracts was assessed via fluorescence quenching of cis-parinaric acid. Both FGs and PAs conferred approximately 2-fold antioxidant protection, with FGs showing a 1.13-fold greater effect than PAs. In addition, both PP classes promoted lipid raft formation, particularly in cholesterol-rich membranes. PPs increased order in the liquid-disordered (Ld) phase while inducing disorder in the liquid-ordered (Lo) phase, depending on the lipid-to-PP ratio. Notably, FGs enhanced membrane fluidity more strongly in A549 than in MDCKII cells, as reflected by a ~5.7-fold decrease in Laurdan GP in A549 (from 0.04 to −0.17) versus a ~1.4-fold decrease in MDCKII at 200 μg/mL. These findings highlight the dual structural and antioxidative roles of FGs and PAs in preserving membrane integrity under oxidative stress. Full article
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20 pages, 1078 KB  
Article
Atherogenic Risk and Its Association with Alcohol Consumption, Lifestyle Habits, and Sociodemographic Factors in a Population of Spanish Workers
by Joan Obrador de Hevia, Ángel Arturo López-González, José Ignacio Ramírez-Manent, Carla Busquets-Cortes, Pedro Juan Tárraga López, Miguel García Samuelsson and Pere Riutord-Sbert
Life 2025, 15(6), 923; https://doi.org/10.3390/life15060923 - 7 Jun 2025
Cited by 1 | Viewed by 1063
Abstract
Atherogenic dyslipidemia is a major contributor to cardiovascular disease, the leading cause of morbidity and mortality worldwide. While lipid abnormalities are well-established clinical risk factors, growing evidence highlights the influence of sociodemographic and lifestyle determinants on lipid profiles. However, large-scale epidemiological data addressing [...] Read more.
Atherogenic dyslipidemia is a major contributor to cardiovascular disease, the leading cause of morbidity and mortality worldwide. While lipid abnormalities are well-established clinical risk factors, growing evidence highlights the influence of sociodemographic and lifestyle determinants on lipid profiles. However, large-scale epidemiological data addressing these associations within occupational settings remain limited. Objective: To assess the cross-sectional and longitudinal associations between atherogenic risk—measured through TC/HDL-c, LDL-c/HDL-c, TG/HDL-c ratios, and atherogenic dyslipidemia (AD)—and sociodemographic variables, health behaviors, and alcohol consumption in a large cohort of Spanish workers. Methods: A dual-phase study was conducted. The first phase was a cross-sectional analysis of 139,634 workers (83,282 men; 56,352 women) from multiple employment sectors undergoing routine occupational health assessments. The second phase was a longitudinal study of a subsample (n = 40,431) with complete data from 2009 and 2019. Clinical, anthropometric, and biochemical data were collected using standardized protocols. Lifestyle factors (smoking, physical activity, Mediterranean diet adherence, alcohol intake) and socioeconomic indicators (education, occupational class) were recorded. Multinomial logistic regression was used to determine independent associations with high-risk atherogenic profiles. Results: Higher atherogenic indices and prevalence of AD were associated with advancing age, lower educational level, lower social class, smoking, physical inactivity, poor diet quality, and alcohol consumption. Men exhibited higher TG/HDL-c and AD values, whereas women had higher TC/HDL-c and LDL-c/HDL-c. Physical inactivity showed the strongest association with TG/HDL-c (OR: 36.23; 95% CI: 32.12–40.35) and AD (OR: 16.86; 95% CI: 14.80–18.93). Alcohol intake also independently predicted higher TG/HDL-c (OR: 1.60) and AD (OR: 1.79). Over the decade, a general increase in atherogenic risk was observed, especially among older adults, socially disadvantaged groups, and those with unhealthy behaviors. Conclusions: Sociodemographic and lifestyle factors, particularly physical inactivity and alcohol consumption, are strongly associated with adverse atherogenic profiles in the working population. The observed rise in lipid-related cardiovascular risk over the past decade emphasizes the urgent need for workplace-based health promotion strategies targeting modifiable behaviors and structural health inequalities. Full article
(This article belongs to the Section Physiology and Pathology)
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18 pages, 1567 KB  
Article
Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis
by Jiheng Xiao, Wei Zhou, Jiatai He, Yanbin Zhu, Yingze Zhang and Liming Xiong
Diagnostics 2025, 15(10), 1287; https://doi.org/10.3390/diagnostics15101287 - 20 May 2025
Cited by 1 | Viewed by 1001
Abstract
Background: Although clinical studies have indicated a possible association between dyslipidemia and osteoporosis, the underlying genetic basis and mechanistic pathways remain insufficiently defined. Most prior research has concentrated on conventional lipid markers, which are prone to confounding and limit causal inference. Exploring [...] Read more.
Background: Although clinical studies have indicated a possible association between dyslipidemia and osteoporosis, the underlying genetic basis and mechanistic pathways remain insufficiently defined. Most prior research has concentrated on conventional lipid markers, which are prone to confounding and limit causal inference. Exploring lipidomic profiles offers a more comprehensive view of lipid metabolism and may reveal novel genetic links beyond traditional lipid traits. Additionally, alterations in immune cell function, often triggered by metabolic disturbances, may contribute to osteoporosis development; however, the potential mediating role of immune cells in the lipid–bone axis has not been systematically investigated. Methods: A total of 179 lipid species across 13 lipid classes were analyzed in 7174 Finnish individuals from the GeneRISK cohort. Genome-Wide Association Study (GWAS) summary statistics for osteoporosis and 731 immune cell immunophenotypes were sourced from the GWAS Catalog. A two-step, two-sample Mendelian randomization analysis, using inverse variance weighting (IVW), was conducted to explore the potential causal effects of lipids on osteoporosis and the mediating role of immune cells in the relationship between lipids and osteoporosis. Results: Mendelian randomization analysis indicated that triacylglycerol levels of 48:0 were possibly associated with an increased risk of osteoporosis (IVW: odds ratio [OR] 1.1320, 95% CI 1.0401–1.2321; p = 0.004), while triacylglycerol levels of 48:3 appeared to be associated with a reduced risk of osteoporosis (IVW: OR 0.9053, 95% CI 0.8364–0.9800; p = 0.014). Two statistically significant mediating effects were identified: First, IgD− CD38dim %B cells appeared to partially negatively mediate the association between triacylglycerol levels of 48:3 and osteoporosis, with a negative mediating effect of −0.00669 (95% CI: −0.0214, 0.00805), which accounted for 6.73% of the total effect. That is, the protective effect of triacylglycerol levels of 48:3 against osteoporosis was attenuated by IgD− CD38dim %B cells. Second, HLA DR++ monocytes% leukocytes also partially negatively mediated this relationship, with a mediating effect of −0.023 (95% CI: −0.0434, −0.00266), accounting for 23.2% of the total effect. This indicates that other immune cells, HLA DR++ monocytes %leukocytes, resisted the protective effect of triacylglycerol levels of 48:3 against osteoporosis, with a weakening effect stronger than that of IgD− CD38dim %B cells. Conclusions: Our findings contribute to the growing understanding of the potential causal relationships and shared pathogenic mechanisms between dyslipidemia and osteoporosis. The results suggest that the potential genetic effects of plasma lipid metabolites on osteoporosis may be partially down-regulated by specific kinds of immune cells. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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12 pages, 393 KB  
Article
Bioactive Lipid Compounds and Nutritional Potential of Glyceride Oils from Flower Buds and Fruits of Lagerstroemia indica L. Cultivar ‘Hopi’ Grown in Bulgaria
by Olga Teneva, Zhana Petkova, Maria Angelova-Romova and Ginka Antova
Foods 2025, 14(9), 1449; https://doi.org/10.3390/foods14091449 - 22 Apr 2025
Cited by 2 | Viewed by 779
Abstract
This study explored the bioactive lipid compounds and assessed the nutritional potential of glyceride oils extracted from flower buds and fruits of Lagerstroemia indica L. cultivar ‘Hopi’ grown in Bulgaria. The study focused on chemical composition, fatty acid composition, and the content of [...] Read more.
This study explored the bioactive lipid compounds and assessed the nutritional potential of glyceride oils extracted from flower buds and fruits of Lagerstroemia indica L. cultivar ‘Hopi’ grown in Bulgaria. The study focused on chemical composition, fatty acid composition, and the content of biologically active compounds of the oils. The results indicated relatively higher levels of glyceride oil in fruits (F), 14.8%, compared to flower buds (FB), 3.3%. A similar trend was observed for protein content—15.7% (F) vs. 8.7% (FB). Total sterol and phospholipid content was higher in the FB than in the F. The primary components of sterol composition were β-sitosterol and campesterol. The main individual phospholipid classes were phosphatidylinositol and phosphatidylcholine in both oils. Linoleic acid was the predominant component (77.3% in the oil from the FB vs. 86.0% in the oil from the F), followed by comparable quantities of oleic acid. Palmitic acid was the main saturated fatty acid. To evaluate the therapeutic effect of isolated glyceride oils, the following indices were measured: index of atherogenicity, thrombogenicity, and hypocholesterolemic/hypercholesterolemic ratio. The study sought to compare the levels of glyceride oil, protein content, total sterol and phospholipid content, and to identify the main components of fatty acids, sterols, and phospholipids in the flower buds and fruits and their oils of L. indica cultivar ‘Hopi’. Full article
(This article belongs to the Section Plant Foods)
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