Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 17, 2025

Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting release pro-inflammatory factors such as cytokines adipokines. These inflammatory mediators circulate through bloodstream, propagating inflammation both periphery central nervous system. Gut dysbiosis, which results leaky intestinal barrier, exacerbates plays significant role linking pathogenesis neurodegeneration gut-brain/gut-brain-liver axis. Inflammatory states within brain can lead insulin resistance, mitochondrial dysfunction, autolysosomal increased oxidative stress. disruptions impair normal neuronal function subsequently cognitive decline motor deficits, similar pathologies observed neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease. Understanding underlying disease mechanisms crucial for developing therapeutic strategies address defects these metabolic pathways. In this review, we summarize provide insights different strategies, methods alter gut lifestyle changes, dietary supplementation, well pharmacological agents derived from natural sources, that target obesity-induced

Язык: Английский

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Obesity Is Associated with Oxidative Stress Markers and Antioxidant Enzyme Activity in Mexican Children

Antioxidants, Год журнала: 2024, Номер 13(4), С. 457 - 457

Опубликована: Апрель 12, 2024

The relationship between metabolic disorders and oxidative stress is still controversial in the child population. present cross-sectional study aimed to analyze associations obesity, cardiometabolic traits, serum level of carbonylated proteins (CPs), malondialdehyde (MDA), enzyme activity catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) children from Mexico City (normal weight: 120; obesity: 81). Obesity resulted being positively associated with CAT (β = 0.05 ± 0.01, p 5.0 × 10−3) GPx 0.13 3.7 10−19) activity. A significant interaction obesity sex was observed MDA SOD enzymatic (PMDA 0.03; PSOD 0.04). level, were only boys (boys: PMDA 3.0 10−3; 7.0 girls: ≥ 0.79). In both normal weight those CP levels (PNormal-weight 2.2 PObesity 0.03). conclusion, Mexican children, activity, its are sex-specific. Therefore, related independently body weight.

Язык: Английский

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Obesity modifies the association between abnormal glucose metabolism and atrial fibrillation in older adults: A community-based longitudinal and prospective cohort study

Hellenic Journal of Cardiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

To investigate the modifying role of obesity in association between abnormal glucose metabolism and atrial fibrillation (AF) risk older individuals. From April 2007 to November 2011, 11663 participants aged ≥60 years were enrolled Shandong area. Glucose metabolic status determined using fasting plasma hemoglobin A1c levels, body mass index (BMI), waist-to-hip ratio (WHR), visceral fat area (VFA). Obesity-associated activities assessed adiponectin-to-leptin (ALR), galectin-3, triglyceride-glucose (TyG). New-onset AF was diagnosed by ICD-10. During an average 11.1 follow-up, 1343 developed AF. risks higher those with prediabetes, uncontrolled diabetes, well-controlled diabetes than normoglycemia. The hazard ratios decreased 14.79%, 40.29%, 25.23% 31.44%, 53.56%, 41.90% 21.16%, 42.38%, 27.59% after adjusting for BMI, WHR, VFA, respectively. population attributable percentage general obesity, central high VFA new-onset 10.43%, 34.78%, 31.30%, ALR, TyG significantly mediated (all Padj. <0.001). Obesity mediates WHR is effective modifier BMI moderating association. TyG, galectin-3 mediate effect on risk.

Язык: Английский

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Single-cell analyses of intestinal epithelium reveal the dysregulation of gut immune microenvironment in systemic lupus erythematosus

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 27, 2025

Abstract Background The small intestine harbors a rich array of intestinal intraepithelial lymphocytes (IELs) that interact with structural cells to collectively sustain gut immune homeostasis. Dysregulation homeostasis was implicated in the pathogenesis multiple autoimmune diseases, however, whether this is disrupted lupus background remains unclear. Methods We performed single-cell RNA sequencing (scRNA-seq) analyses elucidate and milieu epithelium MRL/Lpr mice (Lpr mice) MRL/Mpj control (Mpj mice). Comprehensive including unsupervised clustering, trajectories, cellular communication were performed. primary findings from scRNA-seq further validated by quantitative polymerase chain reaction (qPCR), flow cytometry, vivo experiments selenium supplementation. Results observed significant reduction CD8αα + IELs, accompanied marked increase CD8αβ IELs Lpr mice. Additionally, subsets CD8 exhibiting significantly enhanced effector functions found be markedly enriched Intercellular patterns within epithelial specifically altered Moreover, revealed decreased TCRγδ T (γδT) associated reduced aryl-hydrocarbon receptor repressor ( AHRR ) expression subsequent oxidative stress ferroptosis Antioxidant effectively reversed loss γδT mice, improved barrier, alleviated symptoms. Conclusions Our high-resolution atlas enhances understanding provides new insights into mediated dysregulation.

Язык: Английский

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Association of elevated albumin-corrected anion gap with all-cause mortality risk in atrial fibrillation: a retrospective study

BMC Cardiovascular Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 27, 2025

Compared to the conventional anion gap, albumin-corrected gap (ACAG) offers a more precise measure of acid-base imbalance, providing superior prognostic insight. However, relevance ACAG in individuals atrial fibrillation (AF) remains insufficiently explored. This research seeks evaluate correlation between levels and mortality risk with AF. We identified diagnosed AF from Medical Information Mart for Intensive Care (MIMIC)-IV database. Participants were categorized into quartiles based on their levels. The outcomes included 30 days 365 all-cause mortality. Kaplan-Meier survival curves utilized cumulative across quartiles. applied Cox regression restricted cubic spline analyses prognosis. Subgroup interaction assessments confirm robustness findings. A total 2920 patients (54.93% male) incorporated analysis, 1.61% as having paroxysmal 30-day 365-day rates 22.91% 39.21%, respectively. demonstrated that elevated significantly linked increased (log-rank P < 0.001). In multivariate proportional hazards analyses, independently predicted at both (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.02-1.05; 0.01) (aHR, 1.03; after adjusting potential confounders. positive relationship rising was showed by analysis. revealed no significant interactions (all P-values > 0.05). AF, higher are related greater days. These findings suggest may serve valuable marker patient stratification. Incorporating clinical decision-making could support improved therapeutic strategies enhance outcomes.

Язык: Английский

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Association of the inflammatory burden index with the risk of pre-diabetes and diabetes mellitus: a cross-sectional study

BMC Endocrine Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Март 26, 2025

This study aims to investigate the association between Inflammatory Burden Index (IBI) and prevalence of pre-diabetes (pre-DM) diabetes mellitus (DM) in U.S. population from 1999 2010. By analyzing relevant data collected during this period, seeks understand IBI's role onset pre-DM DM its potential implications for public health. A cross-sectional analysis was conducted using National Health Nutrition Examination Survey (NHANES) total 29,554 participants were included, with status determined by self-reported diagnoses clinical indicators (such as glycosylated hemoglobin fasting blood glucose). The calculated C-reactive protein (CRP) multiplied neutrophil-to-lymphocyte ratio. generalized additive model (GAM) employed examine relationship increasing IBI incidence DM. included participants, 14,290 (48.4%) men 15,264 (51.6%) women, a mean age 48.3 years (SD = 19.1). findings revealed significant risk In fully adjusted model, stronger observed pre-DM, DM, IBI. significantly higher fourth quartile (Q4) compared first (Q1), 26% an 18% when greater than 1.04. Our demonstrates correlation population. Given these findings, we recommend that be considered key indicator management treatment settings.

Язык: Английский

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Polyunsaturated Fatty Acids Improved Long Term Prognosis by Reducing Oxidative Stress, Inflammation, and Endothelial Dysfunction in Acute Coronary Syndromes

Marine Drugs, Год журнала: 2025, Номер 23(4), С. 154 - 154

Опубликована: Апрель 1, 2025

Background: Oxidative stress, inflammation, and endothelial dysfunction are important processes in the progression of atherosclerosis occurrence acute coronary syndromes (ACSs). Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) present marine organisms have capacity to reduce all these and, at same time, emergence ACSs. Aim: To evaluate role PUFAs therapy on parameters oxidative inflammatory syndrome, dysfunction, long-term prognosis syndromes. Methods: One thousand one hundred forty patients were admitted Clinic County Emergency Hospital Brasov with ACS enrolled a prospective study. The study was divided into four groups related type treatment added optimal medical (OMT). effect associated OMT determined by measuring dynamics following parameters: (a) stress—total antioxidant status (TAS), oxidated low density lipoprotein cholesterol antibodies (Ab anti-ox-LDL), IgG anti-Myeloperoxidase (IgG Ab anti-MPO); (b) syndrome—C-reactive protein fibrinogen; (c) dysfunction—flow mediated dilation (FMD) von Willebrand factor (vWf) activity, from baseline 6 months follow-up. Clinical events followed 5 years cardiovascular sudden death, Non-ST ST segment elevation ACS, stent thrombosis restenosis, stroke, readmission hospital for heart failure. Results: In groups, significantly decreased Regarding clinical events, significant reduction risk death incidence in-stent failure, observed PUFA-treated comparison control groups. Conclusions: syndromes, resulted decrease also improvement prognosis.

Язык: Английский

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Higher levels of oxidative balance score linked to lower risk of gallstones: findings from the 2017–2020 National Health and Nutrition Examination Survey

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Янв. 29, 2025

Background and objective The Oxidative Balance Score (OBS) has been linked to various chronic diseases; however, its association with gallstone prevalence remains underexplored. This study aimed investigate the relationship between OBS risk. Methods cross-sectional utilized data from National Health Nutrition Examination Survey (NHANES) conducted 2017 March 2020. Weighted logistic regression models were applied examine of gallstones, complemented by subgroup sensitivity analyses. Restricted cubic spline (RCS) was used nonlinear gallstones. Results A total 5,382 participants included, among whom 592 reported a history After adjusting for confounding factors, significant negative observed (quartile 4 vs. quartile 1: odds ratio [OR] 0.63, 95% confidence interval [CI] 0.43–0.90, p = 0.019). RCS analysis further supported linear risk (nonlinear 0.149). findings analyses exhibited considerable consistency. Conclusion identified risk, suggesting that higher levels are associated reduced likelihood formation.

Язык: Английский

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Controversies and challenges of anticoagulation therapy in obesity

Expert Opinion on Pharmacotherapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

The relationship between anticoagulation efficacy and safety in obesity is complex can vary degrees of anticoagulant choice. Indeed, patients at extremes body weight were under-represented randomized trials. Additionally, the possibility an 'obesity paradox' has been raised atrial fibrillation, describing decreased thromboembolic risk obese patients. We explore current literature on obesity, specifically with regard to venous thromboembolism, bleeding risk. Pharmacodynamic pharmacokinetic considerations are also discussed. As a class, direct oral anticoagulants comparable vitamin-K antagonists preventing treating thromboembolism overweight patients, whilst not increasing

Язык: Английский

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Natural Products Alleviate Atrial Fibrillation by Modulating Mitochondrial Quality Control

Phytomedicine, Год журнала: 2025, Номер 140, С. 156555 - 156555

Опубликована: Фев. 22, 2025

Язык: Английский

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