Search Results (5,823)

Ceramides are central bioactive sphingolipids that regulate diverse cellular processes, including membrane organization, energy metabolism, and stress signaling. Emerging evidence has implicated that ceramide dysregulation is associated with the onset and progression of heart failure. This review introduces the understanding of ceramide metabolism, focusing on its biosynthesis, and functional roles in cardiomyocytes. In addition, the contribution of systemic ceramides derived from circulating lipoproteins and peripheral tissues to cardiovascular risk is also discussed. In parallel, it is highlighted that cardiomyocyte-intrinsic ceramide synthesis plays physiological and pathological roles in the heart. Particularly, excessive ceramide accumulation is detrimental for cardiac function, through multiple mechanisms, such as lipotoxic effects, mitochondrial impairment, inflammation, and cell death. The current review discusses the potential diagnostic and therapeutic strategies targeting ceramide metabolism, as well as the open questions about ceramide association with heart disease. Full article

Background/Objectives: The interplay between cardiovascular risk factors and brain aging remains incompletely understood. We aimed to investigate the comparative associations of coronary artery calcium (CAC) and low-density lipoprotein cholesterol (LDL-C) with MRI-derived volumetric measures of the brain. Methods: In this retrospective, single-center, cross-sectional study, 84 participants who underwent coronary computed tomography for CAC scoring and brain magnetic resonance imaging within 90 days were included; LDL-C levels were available in 69 participants for LDL-based analyses. Brain volumetric measures were obtained using the automated lesionBrain pipeline within the volBrain platform, which performs fully automated tissue segmentation and lesion quantification based on multi-atlas and patch-based approaches. Associations were evaluated using Spearman’s correlation with false discovery rate correction and hierarchical multivariable regression, supported by bootstrap validation and post hoc power analysis. The cohort had a mean age of 58.0 ± 13.0 years (range 19–78) and was derived from routine clinical imaging. Results: LDL-C was positively associated with abnormal white matter volume (ρ = 0.334, p = 0.005), although this did not remain statistically significant after FDR correction (pFDR = 0.090). In fully adjusted models, LDL-C remained the only independent predictor (β = 0.006, 95% CI: 0.002–0.010, p = 0.007; standardized β = 0.225; partial R² = 11.7%), corresponding to a 6.2% increase in abnormal white matter volume per 10 mg/dL increase (derived from log-transformed models). CAC showed only a marginal association (p = 0.059). Post hoc power analysis demonstrated adequate power for LDL-C but insufficient power for CAC. Neither marker was associated with gray matter volume. Conclusions: In this cross-sectional cohort, higher LDL-C was independently associated with greater abnormal white matter volume after adjustment for cardiovascular risk factors, statin use, and CAC. No CAC–brain association was detected in this cohort, but limited statistical power means that small CAC effects cannot be excluded. These findings should be interpreted as associative rather than causal or mechanistic. Full article

Diabetes complications may increase frailty rates among the elderly, leading to falls, immobility, dependency, hospitalizations, and death. The study aimed to assess any association between frailty status and glycaemic control among older adults with type 2 diabetes mellitus at Kenyatta National Hospital, Kenya. We conducted a cross-sectional study of 430 older individuals aged 60+ years with type 2 diabetes at a specialized diabetes clinic using a modified FRAIL scale. Mean age was 69.1 years; 65.7% were female and 76.2% completed primary school. Frailty prevalence was 3.8%, pre-frailty constituted 24.3%, and robust/non-frail comprised 71.9%. It was associated with age, social status, health knowledge, duration of DM, blood pressure, body mass index, high-density lipoprotein-C, and renal failure. Mean fasting plasma glucose (FPG) was 8.7 mmol/L, with 60% having FPG > 7 mmol/L; mean glycated haemoglobin (HbA1C) was 8.0%, with 41% having HbA1C > 8%. Glycaemic control was correlated with number of medications, blood pressure, and lipidaemia, but not age, sex, or social status. No correlation was found between frailty and glycaemic control: frailty versus FPG (r = 0.038, p = 0.459; χ² = 0.699, p = 0.705) and HbA1C (r = −0.009, p = 0.877; χ² = 0.046, p = 0.977). Low frailty prevalence was noted, with no association to glycaemic control. Our findings provide evidence for conducting frailty assessments in chronic disease care. Full article

A 56-day feeding trial was conducted to evaluate the effects of varying dietary lipid and starch levels on growth performance, biochemical components, and hepatic glycolipid metabolism in hybrid grouper. Nine isonitrogenous diets were formulated to contain three levels of lipid (6%, 10%, or 14%) and starch (14%, 21%, or 28%) using a 3 × 3 factorial design. Juvenile fish (initial body weight: 19.06 ± 0.03 g) were randomly allocated to 27 floating net cages (25 fish per cage, three replicates per diet) in an indoor seawater recirculation system and hand-fed to apparent satiation twice daily. Two-way ANOVA was conducted to check treatment effects of dietary lipid and starch levels. No interaction effect between lipid and starch on growth and feed utilization was observed across all treatments; however, significant interactions between the two were observed for condition factor (CF), and some serum biochemical indicators and some hepatic glycolipid metabolic enzyme activities. Growth rate, specific growth rate, and feed efficiency (FE) exhibited a declining trend with increasing dietary lipid levels (p < 0.05). Conversely, hepatosomatic index (HSI), viscerosomatic index (VSI), condition factor, hepatic lipid and glycogen contents, muscle lipid content, serum triglyceride and high-density lipoprotein cholesterol contents, as well as hepatic carnitine palmitoyltransferase 1 (CPT-1) and lipoprotein lipase (LPL) activities, showed an increasing trend (p < 0.05). As lipid levels increased, serum total cholesterol (TC) and total protein (TP) contents dropped to a minimum at the intermediate lipid level (10%) and then rose, regardless of starch level. Hepatic fructose-1,6-bisphosphatase (FBP) activity increased significantly when lipid level rose from 6% to 10% (p < 0.05). With increasing dietary starch levels, HSI, VSI, hepatic and muscle glycogen contents, and serum low-density lipoprotein cholesterol content increased, while FE and serum TP content decreased (p < 0.05). Hepatic CPT-1, LPL, FBP, and pyruvate kinase activities were significantly enhanced when starch levels increased from 14% to 21% or 28% (p < 0.05). Serum aspartate aminotransferase activity was significantly higher in fish fed 14% lipid compared to those fed 6% or 10% lipid. These findings indicate that there is no interaction of dietary lipid and starch on growth and feed utilization, but high dietary lipid (14%) may enhance hepatic lipid oxidation while suppressing glycolysis, thereby limiting growth and promoting hepatic lipid deposition. The results provide a practical reference for optimizing dietary lipid and starch levels in cost-effective feed formulations for hybrid grouper. Full article

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic lipid accumulation and can progress to severe liver injury. Kaempferol (KPF), a plant-derived flavonoid, exhibits lipid-regulatory properties. Tripartite motif-containing protein 56 (TRIM56), an E3 ubiquitin ligase, has been reported to interact with fatty acid synthase (FASN) and limit hepatic lipogenesis. This study investigated whether KPF alleviates NAFLD through modulation of TRIM56-associated lipid metabolic pathways. Molecular docking, molecular dynamics simulations, and cellular thermal shift assays (CETSA) were employed to evaluate the interaction between KPF and TRIM56. High-fat diet-induced NAFLD mice and fatty acid-treated HepG2 cells were used to assess the effects of KPF on hepatic lipid accumulation. Histological analysis, lipid profiling, Oil Red O staining, Western blotting, immunofluorescence, and quantitative PCR were performed. Endogenous co-immunoprecipitation examined the association between TRIM56 and FASN, and siRNA-mediated knockdown of TRIM56 evaluated its functional contribution. KPF significantly reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, ameliorated hepatic steatosis in vivo, and decreased intracellular lipid accumulation in vitro. In silico and CETSA analyses supported the engagement of TRIM56 by KPF. KPF restored TRIM56 expression under steatotic conditions, whereas TRIM56 silencing attenuated its lipid-lowering effects. TRIM56 was confirmed to associate with FASN, and KPF treatment suppressed multiple lipogenic enzymes. These findings indicate that KPF alleviates hepatic steatosis, at least in part, through modulation of TRIM56-associated lipogenic pathways, highlighting TRIM56 as a potential therapeutic target in NAFLD. Full article

This study was conducted to investigate the effects of dietary supplementation with rumen-protected arginine (RP-Arg) on growth performance, rumen fermentation parameters, microbial diversity, and blood physiological and biochemical indices in fattening Altay sheep. A total of 24 healthy, 6-month-old Altay male lambs were randomly assigned to three groups, with eight replicates per group. The control group received a basal diet, while the experimental groups were supplemented with either 0.50% or 1.00% RP-Arg on a dry matter basis, respectively. The results indicated that RP-Arg supplementation had no significant effect on feed intake, growth performance, or slaughter performance of the lambs (p > 0.05), whereas backfat thickness decreased linearly (p < 0.05). With increasing RP-Arg levels, serum low-density lipoprotein cholesterol, leptin, and catalase activity increased linearly (p < 0.05), while blood ammonia, alanine aminotransferase, and Ig M exhibited a significant quadratic increase (p < 0.05). RP-Arg supplementation led to a linear decrease in ruminal propionate and valerate concentrations (p < 0.05). Analysis of bacterial diversity revealed that the class Vampirivibrionia and the order Gastranaerophilales were biomarkers for the 0.50% RP-Arg group, while several taxa within the phyla Proteobacteria and Thermoplasmatota served as biomarkers for the 1.00% RP-Arg group. In summary, although supplementation of a forage-based diet with RP-Arg partially modified rumen microbial composition and fermentation profile, and regulated several blood biochemical parameters, it did not translate into any beneficial effects on growth performance. Larger-scale studies are therefore warranted to further elucidate the role of RP-Arg in fattening lambs. Full article

Background: Metabolic dysregulation is increasingly recognized as a contributor to carcinogenesis; however, the role of circulating lipid traits in ovarian cancer remains unclear. Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, and Embase were searched from inception to March 2026. Observational studies evaluating triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in relation to ovarian cancer risk were included. Random-effects models were used to pool relative risks (RRs). Robustness was assessed via sensitivity analyses, influence diagnostics, and multiverse analysis. Mendelian randomization (MR) evidence was integrated for causal inference. Results: Six observational studies were included in the meta-analysis. Elevated triglyceride levels were associated with increased ovarian cancer risk, while HDL-C showed a modest inverse association. LDL-C and total cholesterol were not significantly associated with risk. Sensitivity analyses excluding early follow-up strengthened the triglyceride association. MR analyses supported a potential causal role for triglycerides but not for HDL-C. Conclusions: Circulating triglycerides may represent a metabolically relevant risk factor for ovarian cancer. Further large-scale prospective and mechanistic studies are warranted. Full article

Pregnancy is characterized by progressive maternal hyperlipidemia, including increased triglycerides, total cholesterol, and low-density lipoprotein, with dynamic fluctuations in high-density lipoprotein. Excess maternal free fatty acids induce oxidative stress through reactive oxygen species, causing mitochondrial dysfunction, lipid peroxidation, activation of inflammatory pathways, and epigenetic remodeling in the placenta and fetal tissues. These molecular alterations impair placental lipid transport and nutrient sensing, leading to hypertrophy of fetal liver, myocardium, and adipose tissue, while disrupting neonatal glucose and lipid homeostasis and increasing susceptibility to perinatal complications and long-term metabolic disorders. This review aims to evaluate mechanistic pathways linking maternal lipid metabolism, oxidative stress, placental function, and fetal organ remodeling. Mechanistic and translational studies were identified through searches of PubMed, Scopus, the Cochrane Library, and Web of Science (2000–2025) using predefined keywords including lipid metabolism, free fatty acids, oxidative stress, placental lipid transport, epigenetics, DNA methylation, fetal programming, and perinatal outcomes. Evidence indicates that maternal lipid imbalance drives placental oxidative and epigenetic modifications, directly contributing to fetal organ hypertrophy and neonatal metabolic dysregulation. In conclusion, maternal dyslipidemia represents a modifiable determinant of fetal organ hypertrophy and long-term metabolic risk, supporting the clinical relevance of maternal lipid monitoring and targeted metabolic interventions during pregnancy. Full article

Background/Objectives: This secondary and exploratory meta-analysis re-evaluated 30 randomized controlled trials on free and added sugars (FS) detailed in the European Food Safety Authority’s (EFSA) report on the tolerable upper intake level for dietary sugars, focusing on the influence of food source (beverages, foods, or mixed) on cardiometabolic and anthropometric health. Methods: The EFSA’s method of analyzing the relative FS intake (difference between treatment and comparator arms, Δ%E^fs) was used, with further adjustment for the reported intake of all sources of FS and energy. The EFSA’s “high vs. low” random-effects meta-analysis comparing groups with the highest and lowest FS intake was replicated, and additional exploratory dose–response meta-regressions (linear and non-linear) were performed, stratified by food source. Given the secondary and observational nature of the analysis, all source-stratified findings should be interpreted as hypothesis-generating, rather than causal. Results: There were no interactions between Δ%E^fs and food source for any outcome, and within a source there were linearly positive and statistically significant regressions for body weight (mixed), low-density lipoprotein cholesterol (LDL-C, foods), and uric acid (beverages). Across 13 outcomes, Δ%E^fs was positively and linearly related to greater fasting glucose, high-density lipoprotein cholesterol (HDL-C), and LDL-C, and non-linearly to body weight. However, the data were limited in their representation of FS intake at typical population levels, and there were insufficient data to investigate the effect of FS from foods on most anthropometric outcomes. Conclusions: Meta-regressive dose–responses revealed little relationship between Δ%E^fs from specific food sources and health outcomes, but such effects might be masked by confounding factors. Future trials that test realistic intakes of FS across diverse food matrices and account for dietary compensation would help to overcome limitations in the body of evidence. Full article

Background/Objectives: The relationship between P-wave dispersion (Pd) and disease status in patients with Familial Mediterranean Fever (FMF) undergoing colchicine treatment is unclear in the literature, and results are contradictory. This study aimed to evaluate P-wave dispersion in patients with Familial Mediterranean Fever receiving regular long-term colchicine treatment and to compare these findings with those of age- and sex-matched individuals without FMF. Methods: A cross-sectional and observational study included 97 individuals with positive FMF and 97 individuals with negative FMF. FMF diagnosis was confirmed according to the Tel-HaShomer criteria, and all patients received regular colchicine treatment and were evaluated during the attack-free period. P maximum, P minimum, and Pd were measured using standard 12-lead electrocardiography (ECG); clinical, laboratory, and drug data were recorded. Pd associations were analyzed using correlation and multivariable regression. Results: Pd was found to be significantly higher in FMF (+) patients (47 vs. 39 ms, p < 0.001). Pd showed a positive correlation with FMF status (r = 0.508, p < 0.001), colchicine dose (r = 0.476, p < 0.001), white blood cell (WBC) (r = 0.209, p = 0.005) and high-density lipoprotein cholesterol (HDL-C) (r = 0.156, p = 0.037) and a negative correlation with calcium channel blocker use (r = −0.245, p = 0.001). In multivariate analysis, FMF increased Pd by 10.17 ms, while calcium channel blockers decreased it by 11.78 ms (p < 0.001). Age, WBC and HDL-C also had independent positive effects on Pd (p < 0.001, p = 0.017, p = 0.040, respectively). Conclusions: These findings suggest that FMF is associated with increased P-wave dispersion despite regular colchicine treatment, indicating persistent subclinical atrial conduction heterogeneity. Full article

Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial “residual inflammatory risk” persists, propelling the search for targeted immunopharmacological interventions. At the forefront of this inflammatory cascade is the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as a central orchestrator of vascular inflammation by linking metabolic dysregulation to the innate immune response. Atherogenic danger signals—such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals—trigger NLRP3 activation through reactive oxygen species (ROS) generation, lysosomal rupture, and potassium efflux. This, in turn, drives the maturation of pro-inflammatory cytokines (IL-1β and IL-18) and initiates macrophage pyroptosis. In this review, we systematically evaluate the immunomodulatory potential of natural products—both complex extracts and single bioactive compounds—in inhibiting the NLRP3 inflammasome axis. We detail the pharmacological mechanisms by which these natural agents intercept inflammatory signaling at multiple stages: suppressing TLR4/NF-κB-mediated priming, scavenging mitochondrial ROS, and restoring autophagic flux via AMPK/mTOR pathways to prevent inflammasome assembly. By critically analyzing these pathways, we highlight natural product-derived inhibitors as a promising class of immunomodulators capable of attenuating atherosclerotic progression and addressing the persistent challenge of residual inflammatory risk. Full article

Saskatoon berry (SB), a traditional food of Indigenous people, has been associated with cardiometabolic benefits in animal models; however, its effects on humans remain unclear. This study investigated the effects of dried SB consumption on cardiometabolic outcomes, gut microbiota, and short-chain fatty acids (SCFAs) profiles in healthy adults. In a 10-week, single-arm, and open-label trial, 20 healthy adults consumed 40 g/day of freeze-dried whole SB. Biochemical measures, physical exams, dietary records, participant feedback, and fecal samples were collected before and after the intervention. Gut microbiota composition and fecal SCFAs were profiled using 16S-rRNA sequencing and gas chromatography–mass spectrometry, respectively. SB intake significantly reduced fasting plasma glucose, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), non-high-density lipoprotein-cholesterol (non-HDL-c), systolic blood pressure, and high-sensitivity C-reactive protein, while increasing dietary fiber intake. Fiber intake was negatively correlated with TC, LDL-c and non-HDL-c (p < 0.05). The relative abundance of fecal Prevotellaceae increased after SB consumption and was positively correlated with multiple fecal SCFAs (p < 0.05–0.0001), while being negatively associated with lipid profiles and blood pressure. No adverse cardiovascular, hepatic, or renal dysfunction were observed; however, the significant increase in sugar intake may pose a risk for elevated blood glucose. Therefore, limiting other high-sugar foods during SB supplementation may be advisable for individuals with glucose intolerance. Overall, SB intake improved glucose and lipid metabolism and lowered blood pressure and inflammatory markers in healthy adults. These cardiometabolic benefits may be mediated by fiber and anthocyanins in SB and through modulation of gut microbiota and SCFA production; however, further confirmation is needed in subsequent randomized controlled trials. Full article

Background/Objectives: Cardiovascular diseases are the leading cause of mortality worldwide, with coronary artery disease (CAD) being the most prevalent. An atherogenic diet contributes to oxidative stress by promoting lipid peroxidation in lipoproteins and cellular membranes, thereby compromising membrane integrity, which is reflected in lower phase angle (PhA) values. Dietary antioxidants play a crucial role in cellular health and in reducing atherosclerotic risk; therefore, the Dietary Antioxidant Index (DAI) is an important measure, as dietary antioxidants may counteract oxidative damage. This study aimed to assess the association between anthropometric, PhA, and biochemical variables across groups classified according to DAI. Methods: This was an analytical cross-sectional study. A total of 107 subjects, with and without CAD, were included. Oxidized LDL (oxLDL) and oxidized HDL (oxHDL) were determined using the ELISA technique. PhA was measured by bioelectrical impedance analysis, and DAI was calculated using the formula proposed by Wright et al. Results: DAI was positively associated with HDL concentrations in women with CAD, indicating that HDL levels increased by 5.8 mg/dL for each unit increase in DAI (R² = 0.625, p = 0.001). Furthermore, for each unit increase in DAI, the TC/HDL ratio decreased by 0.3 (R² = 0.625, p = 0.006), and the LDL/HDL ratio decreased by 0.2 (R² = 0.506, p = 0.012). Conclusions: A higher DAI is associated with a more favorable lipid profile in women with CAD, particularly with higher HDL concentrations and lower TC/HDL and LDL/HDL ratios. Full article

Phospholipid transfer protein (PLTP) is a lipid transfer protein classically studied in the context of plasma lipoprotein metabolism, high-density lipoprotein (HDL) remodeling, and cardiovascular disease risk. PLTP facilitates phospholipid transfer between lipoproteins and regulates HDL particle size and composition through interactions with apolipoprotein A-I and apolipoprotein A-II. While its systemic roles in cholesterol handling, reverse cholesterol transport, and inflammatory signaling are well established, the cell-autonomous functions of PLTP within cardiomyocytes remain poorly defined, particularly in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Extensive experimental and clinical studies demonstrate that PLTP enhances ABCA1-dependent cholesterol efflux primarily by stabilizing ABCA1 at the plasma membrane and by promoting the generation of lipid-poor apolipoprotein A-I and pre-β HDL particles, which serve as efficient cholesterol acceptors; the magnitude of these effects depends on cellular context, PLTP expression levels, and the availability of lipid acceptors. PLTP expression is metabolically regulated and widely distributed across tissues, including macrophages and other non-hepatic cells, supporting roles beyond circulating lipoprotein remodeling. Altered PLTP activity has been linked to atherosclerosis, cardiovascular disease, and inflammatory pathways, underscoring its relevance to cardiac pathophysiology. Emerging evidence further suggests that intracellular cholesterol distribution, rather than total cholesterol content alone, critically influences mitochondrial membrane composition, bioenergetics, and stress signaling in cardiomyocytes. These observations raise the possibility that PLTP-regulated lipid flux may indirectly shape mitochondrial function by modulating cellular cholesterol homeostasis. This review synthesizes current knowledge of PLTP biology, cholesterol metabolism, and lipoprotein remodeling, and integrates these concepts with emerging frameworks in cardiomyocyte lipid metabolism and mitochondrial physiology. We highlight human iPSC-derived cardiomyocytes as a strategic and translationally relevant platform to investigate PLTP’s non-canonical, cell-intrinsic roles, identify critical knowledge gaps, and propose future directions for elucidating how PLTP may influence mitochondrial function in human cardiac cells. Full article

Hypertriglyceridemia is a well-recognized contributor to residual atherosclerotic cardiovascular disease risk and a predisposing factor for acute pancreatitis. Despite the availability of pharmacologic agents and lifestyle interventions, patients with severe and refractory hypertriglyceridemia often fail to achieve adequate control. Recent advances in the molecular understanding of triglyceride metabolism have driven the development of targeted therapies that selectively modulate key regulatory pathways. This study sought to provide an overview of triglyceride regulation, the atherogenic role of remnant lipoproteins, and clinical evidence of emerging triglyceride-lowering therapies. Lipoprotein metabolism is regulated by a complex network of regulatory proteins that include lipoprotein lipase (LPL), apolipoproteins such as apolipoprotein C-III (ApoC-III), and angiopoietin-like proteins (ANGPTLs). Targeting these proteins in the metabolic cascade has shown promising results in reducing triglyceride levels. Emerging therapies such as antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) directed against ApoC-III (volanesorsen, olezarsen, and plozasiran), inhibitors of ANGPTL3 (evinacumab and zodasiran), and fibroblast growth factor 21 (FGF-21) analogs (pegozafermin) have demonstrated substantial triglyceride-lowering efficacy. These agents have achieved reductions in triglyceride levels of up to 80% in clinical trials. Additionally, preliminary evidence suggests that these agents may also reduce the incidence of acute pancreatitis and improve cardiometabolic risk profiles, although dedicated trials are still needed to confirm these outcomes. The therapeutic landscape for hypertriglyceridemia is rapidly evolving. Integrating these novel agents into clinical practice will require individualized treatment plans, sustained lifestyle modification, and careful safety monitoring. Full article