Search Results (208)

Central nervous system (CNS) insulin signaling is involved in a broad array of cardiometabolic physiology, including glucose and lipid metabolism, feeding, energy expenditure, and blood pressure regulation. A key role for hypothalamic neuroendocrine and autonomic centers in regulating insulin-associated cardiovascular and metabolic physiology has been highlighted. However, it is still unclear which CNS site(s) initiate insulin-dependent neural cascades. While some investigations have suggested that circulating insulin can access hypothalamic regions by crossing the blood-brain barrier, other studies point to a necessity of other brain areas upstream of the hypothalamus to initiate central insulin actions. In this context, accumulating evidence points to a possible involvement of the sensory circumventricular organs (CVOs), unique areas located outside of the blood-brain barrier, in insulin-dependent cardiometabolic homeostasis. Here, the multifaceted roles for the sensory CVOs in cardiovascular and metabolic regulation, with a special emphasis on insulin receptor pathways, are discussed. Full article

Background/Objectives: Obesity, a major risk factor for cardiometabolic traits, is influenced by both genetic and environmental factors. Genetic studies have identified multiple single-nucleotide polymorphisms (SNPs) associated with obesity and related traits. This study aimed to examine the association between genetic risk score (GRS) and obesity-associated traits, while incorporating SNPs with established gene–diet interactions to explore their potential role in precision nutrition (PN) strategies. Methods: A total of 4279 participants were stratified into low- and intermediate-/high-GRS groups based on 18 SNPs linked to obesity and cardiometabolic traits. This study followed a case–control design, where cases included individuals with overweight/obesity, T2DM-positive (+), or CVD-positive (+) individuals and controls, which comprised individuals free of these traits. Logistic regression area under the curve (AUC) models were used to assess the predictive power of the GRS and traditional risk factors on BMI, T2DM and CVD. Results: Individuals in the intermediate-/high-GRS group had higher odds of being overweight or obese (OR = 1.23, CI: 1.03–1.48, p = 0.02), presenting as T2DM+ (OR = 1.56, CI: 1.03–2.49, p = 0.03) and exhibiting CVD-related traits (OR = 1.56, CI: 1.25–1.95, p < 0.0001), compared to the low-GRS group. The GRS was the second most predictive factor after age for BMI (AUC = 0.515; 95% CI: 0.462–0.538). The GRS also demonstrated a predictive power of 0.528 (95% CI: 0.508–0.564) for CVD and 0.548 (95% CI: 0.440–0.605) for T2DM. Conclusions: This study supports the potential utility of the GRS in assessing obesity and cardiometabolic risk, while emphasizing the potential of PN approaches in modulating genetic susceptibility. Incorporating gene–diet interactions provides actionable insights for personalized dietary strategies. Future research should integrate multiple gene–diet and gene–gene interactions to enhance risk prediction and targeted interventions. Full article

Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Endocrine disorders such as hypercortisolism, hypothyroidism, and polycystic ovary syndrome (PCOS) are closely linked to MASLD through shared metabolic pathways. Mechanisms include glucocorticoid-induced gluconeogenesis and lipolysis, impaired lipid clearance in hypothyroidism, and the hyperandrogenism-induced downregulation of hepatic low-density lipoprotein (LDL) receptors. PCOS-related factors—such as central obesity, adipocyte hypertrophy, low adiponectin levels, and genetic predisposition—further promote hepatic steatosis. Thyroid dysfunction may also impair the hepatic deiodination of T4, contributing to lipid accumulation and inflammation. Given the overlapping pathophysiology among endocrine, hepatic, and reproductive disorders, multidisciplinary collaboration is essential to optimize diagnosis, treatment, and long-term cardiometabolic outcomes. Full article

Background/Objectives: Cardiovascular diseases remain the leading cause of global mortality, with the gut microbiome emerging as a critical factor. This study aimed to characterize gut microbiome composition and metabolic pathways in individuals with low cardiovascular risk (LCR) compared to healthy controls to reveal insights into early disease shifts. Methods: We performed shotgun metagenomic sequencing on fecal samples from 25 LCR individuals and 25 matched healthy controls. Participants underwent a comprehensive cardiovascular evaluation. Taxonomic classification used MetaPhlAn 4, and functional profiling employed HUMAnN 3. Results: Despite similar alpha diversity, significant differences in bacterial community structure were observed between groups (PERMANOVA, p < 0.05). The LCR group showed enrichment of Faecalibacterium prausnitzii (p = 0.035), negatively correlating with atherogenic markers, including ApoB (r = −0.3, p = 0.025). Conversely, Fusicatenibacter saccharivorans positively correlated with ApoB (r = 0.4, p = 0.006). Metabolic pathway analysis revealed upregulation of nucleotide biosynthesis, glycolysis, and sugar degradation pathways in the LCR group, suggesting altered metabolic activity. Conclusions: We identified distinct gut microbiome signatures in LCR individuals that may represent early alterations associated with cardiovascular disease development. The opposing correlations between F. prausnitzii and F. saccharivorans with lipid parameters highlight their potential roles in cardiometabolic health. These findings suggest gut microbiome signatures may serve as indicators of early metabolic dysregulation preceding clinically significant cardiovascular disease. Full article

Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article

The transsulfuration pathway plays a central role in the regulation of sulfur metabolism and contributes to the maintenance of cellular homeostasis. Starting from homocysteine, a sulfur-containing amino acid derived from methionine via the methionine cycle, this metabolic pathway supports the biosynthesis of cysteine and other downstream products, such as taurine, serine, reduced glutathione and the gasotransmitter hydrogen sulfide (H₂S). The most common disruption of this pathway leads to hyperhomocysteinemia (HHcy), a well-known risk factor for the development of cardiometabolic diseases and other pathological conditions. In this context, identifying effective pharmacological strategies is crucial. Based on both preclinical and clinical evidence, this review provides an updated overview on the role of folates in restoring transsulfuration balance in HHcy and explores the potential effects of downstream products (such as serine, taurine, and precursors of glutathione) under HHcy conditions. Finally, it examines the pharmacological properties of H₂S-donors in cultured cells exposed to HHcy and in animal models of HHcy. This summary of the literature offers new perspectives for the treatment of HHcy and the prevention of its associated multiorgan complications. Full article

The causal nature of sex hormone-binding globulin (SHBG) in the pathogenesis of stroke remains uncertain. We explored whether SHBG levels are causally associated with stroke via cardiometabolic traits. A network two-sample Mendelian randomization (MR) study was conducted to determine the mediating roles of cardiometabolic traits in the causal effects of SHBG levels on stroke subtypes. Further two-sample MR analyses were performed to explore the inverse associations between significant cardiometabolic mediators and SHBG levels. The MR results indicated a protective effect of genetically increased SHBG levels on any stroke (odd ratio [OR] = 0.941; 95% confidence interval [CI]: 0.898, 0.984), any ischemic stroke (OR = 0.951; 95% CI: 0.922, 0.981), and small-vessel stroke (OR = 0.871; 95% CI: 0.765, 0.977). Moreover, genetically elevated SHBG levels were associated with lower waist circumference (WC, β = −0.091; 95% CI: −0.136, −0.046), waist-to-hip ratio (WHR, β = −0.057; 95% CI: −0.084, −0.030), triglycerides (TG, β = −0.188; 95% CI: −0.249, −0.127), systolic blood pressure (β = −0.799; 95% CI: −1.068, −0.530), and diastolic blood pressure (β = −0.436; 95% CI: −0.605, −0.267), and a reduced risk of type 2 diabetes mellitus (OR = 0.684; 95% CI: 0.400, 0.968) in both the discovery and replication datasets. The proportions of such cardiometabolic traits that mediated the causal effects of SHBG levels on any stroke, any ischemic stroke, or small-vessel stroke ranged from 17.8% to 52.7%; while the mediating effects of SHBG levels on the causal associations between WC, WHR, and TG and stroke ranged from 18.4% to 68.3%. Our findings suggest a protective effect of genetically elevated SHBG levels on stroke risk via key cardiometabolic mediators, primarily WC, WHR, and TG. The mediating roles of SHBG levels in the causal links from WC, WHR and TG to stroke risk were also established. These pathways support SHBG as a potential biomarker and therapeutic target in stroke prevention. Full article

Overnutrition is a predominant issue in contemporary society, increasing rapidly despite considerable progress in our comprehension of nutrition, the health consequences of different food categories, and the dangers linked to excessive calorie consumption. The pathways connecting obesity to associated disorders are intricate, although research has consistently identified oxidative stress as a principal facilitator of the progression of many diseases. In this paper, the synthesis of various reactive species at the molecular level is studied, and the influence of diet on their production is assessed, with a thorough examination of the cellular mechanisms involved. Furthermore, the correlation between oxidative stress and the development of cardiometabolic diseases is explored, highlighting the most recent and relevant research in the field. Full article

Olive oil (OO) has longstanding significance in human history, particularly in the Mediterranean region, where it has been a cornerstone of diet, economy, and culture. This history adds to modern evidence-based knowledge. Background: The Mediterranean diet (MD), rich in plant-based foods and OO, has been extensively associated with improved cardiometabolic and cognitive health. Recent interest has emerged in understanding how intermittent fasting protocols may enhance these effects. Still, the quality of OO does not only lie in the extraction process; it is also dependent on the tree variety, the soil, and the agricultural practices, ending with the way in which the finished product is stored and consumed. Objectives: This review explores the synergistic potential between OO consumption and intermittent fasting, focusing on their combined impact on metabolic health, oxidative stress, and inflammatory pathways. Methods: A literature search was conducted using multiple databases to identify studies addressing the health effects of OO, fasting, and the MD. Both human and relevant preclinical studies were considered, with emphasis on those evaluating inflammatory markers, lipid metabolism, insulin sensitivity, and neuroprotective mechanisms. Results: Evidence suggests that the bioactive compounds in EVOO may potentiate the benefits of fasting by enhancing antioxidant capacity, reducing postprandial inflammation, and modulating gene expression related to cellular metabolism. Combined, these factors may support improved insulin sensitivity, reduced oxidative damage, and delayed onset of age-related diseases. Conclusions: Understanding the integrative role of OO and fasting within the MD framework could offer valuable insights for nutritional strategies aimed at preventing metabolic syndrome, type 2 diabetes, and neurodegeneration. These findings also support the need for future clinical trials exploring the timing, dosage, and dietary context in which these interventions are most effective. Full article

Introduction: Olive oil’s health benefits are widely known and extensively documented; its advantages are widespread, covering numerous areas of human health. Clinical and experimental data indicate that a Mediterranean Diet (MedDiet) with Extra Virgin Olive Oil (EVOO) lowers the risk of illnesses associated with oxidative stress, chronic inflammation, and weakened immunity, including cancer and cardiovascular disease (CVD). The European Food Safety Authority (EFSA) confirms that olive oil’s polyphenols help protect blood lipids against oxidative damage; thus, EVOO, crucial in the MedDiet, could be a functional food component. Olive oils must contain at least 5 mg of Hydroxytyrosol (HYTY) and its derivatives (oleuropein and Tyrosol (TY)) per 20 g to qualify for the EFSA-approved health claim. To provide a summary of clinical study results, this systematic review assessed the impact of Virgin olive oil (VOO) consumption on cardiovascular risk and disease prevention. Methods: The systematic review’s studies were collected from PubMed, Cochrane, Web of Science, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Population Intervention Comparison Outcome Population (PICO) framework. Results: Seventeen clinical studies were identified, which highlighted the association between VOO consumption (including EVOO) and a reduced risk of cardiovascular disease. Particularly, improvements in biomarkers involved in cardiometabolic pathways and subsequent cardiovascular events were recorded. The beneficial effect was attributed to the polyphenols contained in EVOO. Indeed, EVOO supplementation as part of the Mediterranean diet could improve patients’ quality of life in secondary prevention by demonstrating a positive correlation with the cardioprotective role of polyphenols. Discussion: A balanced diet with VOO represents a simple yet potent method to counteract metabolic dysfunctions associated with CVD. Despite these results, further multicenter clinical studies with a wider range of patients are required to confirm and better understand EVOO’s effects on the prevention of cardiovascular risk. Full article

Background: Childhood obesity is a growing global health concern. Metabolomics, the comprehensive study of metabolites within biological systems, offers a powerful approach to better define the phenotype and understand the complex biochemical alterations associated with obesity. The aim of this systematic review was to summarize current knowledge in the field of metabolomics in childhood obesity and to identify metabolic signatures or biomarkers associated with overweight/obesity (Ov/Ob) and Metabolically Unhealthy Obesity (MUO) in children and adolescents. Methods: We performed a systematic search of Medline and Scopus databases according to PRISMA guidelines. We included only longitudinal prospective studies or randomized controlled trials with ≥12 months of follow-up, as well as meta-analyses of the above that assessed the relation between metabolic signatures related to obesity and Body Mass Index (BMI) or other measures of adiposity in children and adolescents aged 2–19 years with overweight or obesity. Initially, 595 records were identified from PubMed and 1565 from Scopus. After removing duplicates and screening for relevance, 157 reports were assessed for eligibility. From the additional search, 75 new records were retrieved, of which none were eligible for our study. Finally, 7 reports were included in the present systematic review (4 reporting on Ov/Ob and 4 on MUO). Results: The presented studies suggest that the metabolism of amino acids and lipids is primarily affected by childhood obesity. Metabolites like glycoprotein acetyls, the Apolipoprotein B/Apolipoprotein A-1 ratio, and lactate have emerged as potential biomarkers for insulin resistance and metabolic syndrome, highlighting their potential value in clinical applications. Conclusions: There is a need for future longitudinal studies to assess metabolic changes over time, interventional studies to evaluate the efficacy of therapeutic strategies, and large-scale population studies to explore metabolic diversity across different demographics. Our findings reveal specific biomarkers in the amino acid and lipid pathway that may serve as early indicators of childhood obesity and its associated cardiometabolic complications. Full article

Mitochondria play a central role in energy metabolism and continuously adapt through dynamic processes such as fusion and fission. When the balance between these processes is disrupted, it can lead to mitochondrial dysfunction and increased oxidative stress, contributing to the development and progression of various cardiometabolic diseases (CMDs). Their role is crucial in diabetes mellitus (DM), since their dysfunction drives β-cell apoptosis, immune activation, and chronic inflammation through excessive ROS production, worsening endogenous insulin secretion. Moreover, sympathetic nervous system activation and altered dynamics, contribute to hypertension through oxidative stress, impaired mitophagy, endothelial dysfunction, and cardiomyocyte hypertrophy. Furthermore, the role of mitochondria is catalytic in endothelial dysfunction through excessive reactive oxygen species (ROS) production, disrupting the vascular tone, permeability, and apoptosis, while impairing antioxidant defense and promoting inflammatory processes. Mitochondrial oxidative stress, resulting from an imbalance between ROS/Reactive nitrogen species (RNS) imbalance, promotes atherosclerotic alterations and oxidative modification of oxidizing low-density lipoprotein (LDL). Mitochondrial DNA (mtDNA), situated in close proximity to the inner mitochondrial membrane where ROS are generated, is particularly susceptible to oxidative damage. ROS activate redox-sensitive inflammatory signaling pathways, notably the nuclear factor kappa B (NF-κB) pathway, leading to the transcriptional upregulation of proinflammatory cytokines, chemokines, and adhesion molecules. This proinflammatory milieu promotes endothelial activation and monocyte recruitment, thereby perpetuating local inflammation and enhancing atherogenesis. Additionally, mitochondrial disruptions in heart failure promote further ischemic injury and excessive oxidative stress release and impair ATP production and Ca²⁺ dysregulation, contributing to cell death, fibrosis, and decreased cardiac performance. This narrative review aims to investigate the intricate relationship between mitochondrial dysfunction and CMDs. Full article

Background: Late-onset pre-eclampsia (LO-PE) remains difficult to predict because placental angiogenic markers perform poorly once maternal cardiometabolic factors dominate. Methods: We reanalyzed a publicly available cell-free RNA (cfRNA) cohort (12 EO-PE, 12 LO-PE, and 24 matched controls). After RNA-seq normalization, we derived LO-PE candidate genes using (i) differential expression and (ii) elastic-net feature selection. Predictive accuracy was assessed with nested Monte-Carlo cross-validation (10 × 70/30 outer splits; 5-fold inner grid-search for λ). Results: The best LO-PE elastic-net model achieved a mean ± SD AUROC of 0.88 ± 0.08 and F1 of 0.73 ± 0.17—substantially higher than an EO-derived baseline applied to the same samples (AUROC ≈ 0.69). Enrichment analysis highlighted immune-tolerance and metabolic pathways; three genes (HLA-G, IL17RB, and KLRC4) recurred across >50% of cross-validation repeats. Conclusions: Plasma cfRNA signatures can outperform existing EO-based screens for LO-PE and nominate biologically plausible markers of immune and metabolic dysregulation. Because the present dataset is small (n = 48) and underpowered for single-gene claims, external validation in larger, multicenter cohorts is essential before clinical translation. Full article

Obesity and cardiometabolic diseases (CMDs) have reached epidemic levels. Dysregulation of lipid metabolism is a risk factor for obesity and CMDs. Lipids are energy substrates, essential components of cell membranes, and signaling molecules. Fatty acids (FAs) are the major components of lipids and are classified based on carbon chain length and number, position, and stereochemistry of double bonds. They exert differential impacts on CMDs, such that saturated fat increases risks while very-long-chain n-3 FAs provide benefits. The functionalities of FAs, modulating membrane properties, acting as ligands for receptors, and serving as precursors for lipid mediators, are vital for insulin signaling, lipid metabolism, oxidative stress, and inflammatory response, collectively contributing to cardiometabolic health. This review examines recent advances in the characteristics and functional properties of different FAs in lipid structures, signaling pathways, and cellular metabolism to better understand the differential roles of different types of FAs in obesity and cardiometabolic health. Full article

Gal-3, also known as galectin-3, a lectin that binds β-galactosides, has gained attention as a novel biomarker and pathophysiological mediator in cardiovascular disease, where it contributes to inflammation, fibrosis, metabolic dysregulation and cardiac remodeling. This narrative review, developed following SANRA (Scale for the Assessment of Narrative Review Articles) guidelines, aims to integrate current clinical and experimental findings on gal-3 into the American Heart Association Life’s Simple 7 (LS7) and Life’s Essential 8 (LE8). By thematically organizing our review across modifiable domains of cardiovascular health, including glucose regulation, lipid metabolism, physical activity, blood pressure, diet, sleep, tobacco use, and body weight (BMI, body mass index), we highlight the role of gal-3 in linking environmental, behavioral and molecular risk factors to cardiometabolic outcomes. Particular attention is given to the oxidative stress, inflammatory–fibrotic axis, and immune activation as mechanistic pathways underlying gal-3-associated cardiovascular damage. We also discuss its relevance to public health and prevention, considering gal-3’s potential for early risk stratification, monitoring lifestyle interventions and personalized prevention strategies. This review bridges molecular mechanisms with clinical and public health relevance, particularly in the context of environmental and lifestyle-related cardiovascular risk. Full article