Search Results (946)

Atrial fibrillation (AF) and diabetes mellitus frequently coexist and together define a high-risk cardiometabolic phenotype. Diabetes is associated with an increased incidence of AF, although this relationship is strongly influenced by obesity, hypertension, chronic kidney disease (CKD), heart failure (HF), sleep-disordered breathing, and broader metabolic risk clustering. Once AF develops, diabetes is associated with greater thromboembolic and HF risk, impaired quality of life, cognitive vulnerability, and excess mortality. These adverse outcomes may be partly explained by a multidimensional atrial substrate, described here within the conceptual framework of diabetic atrial cardiomyopathy, in which hyperglycaemia, insulin resistance, glycaemic variability, oxidative stress, inflammation, autonomic dysfunction, microvascular disease, lipotoxicity, and epicardial adipose tissue dysfunction may contribute to atrial fibrosis, electrical heterogeneity, impaired calcium handling, mitochondrial injury, and mechanical dysfunction. Collectively, these abnormalities may facilitate AF initiation, persistence, progression, and recurrence after rhythm-control interventions. Management should therefore extend beyond rhythm control and anticoagulation alone. In individuals at increased risk of AF, priorities include cardiometabolic optimization, treatment of obesity, hypertension, CKD, HF, and sleep apnoea, lifestyle intervention, and selective rhythm surveillance. In subclinical AF, decisions regarding anticoagulation should account for AF burden, thromboembolic and bleeding risk, renal function, frailty, and patient preference. In established AF, stroke prevention, symptom-directed rate or rhythm control, cardiometabolic therapy, and longitudinal reassessment remain central. This narrative review integrates the epidemiology, mechanisms, and management of AF in diabetes across the continuum from AF risk to subclinical and clinical disease. Full article

Purpose: Obesity is a chronic multifactorial disease whose increasing prevalence cannot be fully explained by excessive caloric intake and sedentary behaviour alone. This review aimed to synthesize current evidence on the role of endocrine-disrupting chemicals (EDCs), particularly obesogenic EDCs, as potential environmental contributors to obesity-related phenotypes, with emphasis on their main classes, etiopathogenetic mechanisms and clinical implications. Methods: A structured literature analysis was conducted using PubMed, Web of Science and additional relevant scientific reports and governmental publications. Eligible sources included original research articles, systematic reviews, meta-analyses and authoritative reports addressing endocrine disruption, obesogens, obesity, metabolic dysfunction and related molecular mechanisms. Results: The review identified several major classes of obesogenic EDCs, including organotins, bisphenols, phthalates and persistent organic pollutants. These compounds have been linked to obesity-related phenotypes through overlapping mechanisms, including disruption of adipogenesis via estrogen receptor-dependent and independent pathways, PPARγ/RXR activation, altered adipokine signalling, neuroendocrine dysregulation across developmental stages, oxidative stress and pro-inflammatory activation, genetic and epigenetic alterations, gut microbiota-mediated effects and impaired thermoregulation through brown and beige adipose tissue dysfunction. EDC-associated obesity may contribute to metabolic, endocrine, cardiovascular, hepatic and reproductive complications. Conclusion: Obesogenic EDCs should be regarded as environmental contributors to obesity that act through interconnected molecular, cellular and systemic pathways. Their biological effects support the need for further mechanistic and epidemiological research, preventive strategies, public education and regulatory measures aimed at reducing exposure. Full article

Obesity is increasingly recognized as a complex systemic disorder rather than a simple consequence of excess energy intake and fat accumulation. This review presents a systems biology framework that examines how obesity-driven disruption of inter-organ communication networks contributes to chronic disease susceptibility, with particular emphasis on colorectal cancer (CRC). Disrupted signaling among the brain, adipose tissue, liver, skeletal muscle, gut, and immune system generates maladaptive feedback loops that promote chronic metabolic inflammation (metaflammation), loss of physiological resilience, and progressive metabolic dysfunction. Within this framework, obesity is redefined as a network disease characterized by neuroendocrine dysregulation, adipose tissue remodeling, immune dysfunction, impaired organ crosstalk, and alterations in the gut microbiome. A central feature of this dysregulation is persistent low-grade inflammation driven by immune-metabolic reprogramming and sustained activation of inflammatory pathways. Obesity-associated metaflammation is further linked to accelerated biological aging through mechanisms involving cellular senescence, mitochondrial dysfunction, oxidative stress, and impaired metabolic resilience. These interconnected processes create a tumor-promoting environment by enhancing oncogenic signaling, disrupting intestinal barrier integrity, altering microbial and metabolic signaling, impairing immune surveillance, and promoting epithelial dysfunction, thereby increasing susceptibility to CRC. The review also examines how behavioral, circadian, environmental, and socioeconomic factors influence metabolic health and cancer risk. Finally, emerging translational opportunities, including biomarker-guided risk stratification, precision prevention, metabolic network restoration, and integrative lifestyle and pharmacological interventions, are discussed. Collectively, this review reframes obesity as a whole-body regulatory disorder and provides an integrated conceptual framework linking metabolism, inflammation, aging, and colorectal carcinogenesis to inform future prevention and therapeutic strategies. Full article

Coronary artery vasospasm (CAV) is a transient, reversible constriction of the epicardial coronary arteries that reduces coronary blood flow and may cause myocardial ischemia. Despite its clinical significance, CAV remains underdiagnosed and can present as chest pain, acute coronary syndrome, malignant arrhythmias or sudden cardiac death. Vasospasm may occur in both angiographically normal coronary arteries and at sites of pre-existing atherosclerotic stenosis. The pathophysiology of CAV is multifactorial and involves vascular smooth muscle cells (VSMCs) hyperreactivity, endothelial dysfunction, chronic inflammation and autonomic dysregulation. VSMCs contraction is mediated by phosphorylation of the myosin light chain (MLC) through calcium (Ca²⁺)/calmodulin-dependent myosin light chain kinase (MLCK), while relaxation is regulated by myosin light chain phosphatase (MLCP). Increased intracellular Ca²⁺ levels and enhanced Ca²⁺ sensitivity contribute to excessive vasoconstriction. Rho-kinase (ROCK) plays a pivotal role in sustained vasospasm by inhibiting MLCP, thereby promoting prolonged smooth muscle contraction. Endothelial dysfunction contributes to CAV by disrupting normal vascular tone regulation, largely as a result of decreased nitric oxide (NO) mediated vasodilation. Chronic low-grade inflammation and oxidative stress exacerbate both endothelial dysfunction and VSMCs contraction. Understanding these molecular mechanisms is essential for identifying novel therapeutic targets. Emerging treatment strategies, including ROCK inhibitors, endothelin receptor antagonists and anti-inflammatory agents, may improve outcomes in patients with refractory CAV. Full article

Type 2 diabetes mellitus (T2DM) is a highly prevalent and devastating chronic metabolic disease worldwide, with pathogenesis centrally characterized by insulin resistance and pancreatic β-cell dysfunction. Accumulating evidence has demonstrated that glucose metabolic reprogramming represents an adaptive metabolic shift from oxidative phosphorylation to aerobic glycolysis in cells in response to a hyperglycemic microenvironment. This shift acts as an upstream important event driving the initiation and progression of T2DM. This review summarizes the characteristics of glucose metabolic reprogramming in insulin-sensitive target organs under T2DM conditions, including the liver, skeletal muscle, adipose tissue and pancreatic β-cells. It also discusses four major downstream effector mechanisms: mitochondrial energy metabolism disturbance, augmented oxidative stress, disruption of mitochondria-associated endoplasmic reticulum membranes (MAMs) coupled with calcium homeostasis imbalance, and systemic inflammatory response. On this basis, we summarize the intervention strategies targeting the above signaling pathways, including antioxidant therapy, restoration of MAMs integrity and calcium homeostasis, systemic anti-inflammatory intervention, and multi-target regulatory effects of traditional Chinese medicine. Current studies indicate that early intervention in downstream stress events is induced by glucose metabolic reprogramming. This is particularly true for the preservation of MAMs’ integrity; restoration of calcium homeostasis; and inhibition of NLRP3 inflammasome activation, the latter of which is expected to block or delay the progression from prediabetes to clinical T2DM. Nevertheless, substantial gaps still remain in the understanding of the dynamic regulatory mechanisms of MAMs, tissue-specific therapeutic targets, and relevant clinical translational research. Future integration of multi-omics technologies will provide novel therapeutic strategies and theoretical foundations for the early prevention and treatment of T2DM. Full article

Adipose tissue remodeling is a dynamic process essential for metabolic homeostasis, enabling tissue expansion, extracellular matrix (ECM) turnover, angiogenesis, and coordinated immune adaptation. In obesity, however, maladaptive remodeling characterized by fibrosis, chronic low-grade inflammation, and hypoxia disrupts adipose plasticity and promotes systemic insulin resistance. Central to these processes is the tightly regulated homeostasis between proteases and their inhibitors, in which the serine protease inhibitor (serpin) superfamily represents an important yet underappreciated regulatory axis. Beyond their classical roles in coagulation and fibrinolysis, serpins regulate ECM remodeling, macrophage recruitment and polarization, cytokine signaling, angiogenic responses, adipokine activity, and insulin sensitivity, thereby orchestrating immune–metabolic crosstalk within adipose depots. Emerging evidence indicates that individual serpins exert distinct and context-dependent effects, with some promoting fibrosis, inflammation, and metabolic dysfunction, whereas others preserve adipose tissue homeostasis and metabolic function. This review synthesizes current knowledge on the structural and functional diversity of the serpin superfamily and examines their mechanistic roles in adipose tissue remodeling during obesity, with particular emphasis on how adipose-associated serpins regulate adipose tissue homeostasis, depot-specific remodeling, and immune–metabolic crosstalk. The review further discusses the experimental and translational applications of emerging single-cell and spatial transcriptomics, multi-omics, and computational approaches that may advance the understanding of serpin biology, improve the investigation of human adipose tissue, and accelerate the identification of clinically relevant serpin-related biomarkers and therapeutic targets for obesity and related metabolic disorders. By positioning serpins as key regulators of adipose tissue remodeling and immune–metabolic integration, this review highlights protease–antiprotease balance as a central determinant of metabolic health and identifies serpins as promising biomarkers and therapeutic targets for obesity and related metabolic disorders. Full article

Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly prevalent and now recognized as a systemic syndrome with diverse clinical phenotypes and multiorgan involvement. The predominant clinical phenotype has evolved from patients with isolated hypertensive heart disease to individuals with cardiometabolic (CM) abnormalities [obesity, insulin resistance, increased waist circumference (a surrogate for visceral adiposity), dyslipidemia, type 2 diabetes, and hypertension] that result in metabolic alterations leading to CM-HFpEF. Indeed, CM-HFpEF and metabolic dysfunction-associated fatty liver disease are recognized as two sides of the same coin. Chronic systemic inflammation is a defining pathophysiologic feature of CM-HFpEF, with visceral adipose tissue serving as a central driver. In this regard, lifestyle changes, including diet and exercise, are crucial for managing HFpEF. Several recent studies have shown that exercise training (aerobic and resistance combined) with or without calorie restriction is an effective therapeutic management strategy for improving exercise capacity, physical function, and quality of life in patients with clinically stable HFpEF. Also, the pharmacologic interventions that have proven beneficial in HFpEF so far (sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists) are effective due to their metabolic protective effects. In this review, we outline the current available evidence on lifestyle interventions in HFpEF management and therapeutics, discussing their modalities and potential mechanisms. Full article

Obesity is a major global health challenge strongly associated with increased cardiometabolic morbidity and mortality. In men, obesity is characterized by a predominance of visceral adiposity, which is metabolically active and closely linked to systemic inflammation, hormonal dysregulation, and adverse cardiovascular outcomes. Despite its clinical relevance, male obesity remains underrecognized as a distinct pathophysiological condition. This study aimed to analyze the inflammatory mechanisms underlying male obesity and their relationship with cardiometabolic risk. A structured narrative review was conducted based on a PICo-guided research question, with literature searches performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, covering publications from 2015 to 2026. Studies focusing on male obesity, inflammatory pathways, and cardiometabolic outcomes were included. Evidence indicates that visceral adipose tissue acts as an active endocrine organ, releasing pro-inflammatory cytokines such as TNF-α and IL-6, contributing to chronic low-grade inflammation. This inflammatory state is associated with insulin resistance (IR), endothelial dysfunction, and oxidative stress, mediated by intracellular pathways including NF-κB and JNK. Additionally, adipokine imbalance, characterized by reduced adiponectin and increased leptin levels, further exacerbates metabolic and vascular impairment. Hormonal alterations, particularly reduced testosterone levels, play a key role in amplifying visceral fat accumulation and inflammation, creating a bidirectional relationship between hypogonadism and metabolic dysfunction. Clinically, these mechanisms highlight the importance of integrating inflammatory biomarkers, body composition assessment, and hormonal evaluation into the management of male obesity. Emerging therapies, including GLP-1 receptor agonists and immunometabolic interventions, offer promising strategies for reducing cardiometabolic risk. In conclusion, male obesity represents a complex, inflammation-driven condition requiring a comprehensive and mechanism-based approach to improve clinical outcomes and guide future therapeutic developments. Full article

Background/Objectives: Obesity-associated metabolic dysfunction involves oxidative stress, gut barrier impairment, and gut–liver axis disruption. This study evaluated whether enzymatically prepared Solenocera crassicornis peptides (SCPs) provide additional benefits during diet normalization in HFD-induced obese mice and examined associations with antioxidant, microbial, and barrier markers. Methods: SCPs were characterized using UPLC-Q-TOF-MS/MS and amino acid analysis. Peptides underwent bioactivity prediction and Keap1 docking. After 7 weeks of HFD feeding, obese male C57BL/6J mice were switched to a normal diet and administered vehicle, orlistat, or SCPs for 4 weeks. Adipose tissue mass, serum lipid profiles, liver histology, hepatic antioxidant status, barrier-associated histological and biochemical markers, and gut microbiota composition were assessed. A simulated digestion–fecal fermentation model was used to assess the effects of fermentation products generated in the presence of digested SCPs on H₂O₂-induced oxidative injury and MUC2 secretion in LS174T goblet-like cells. Results: SCPs reduced epididymal and perirenal fat, improved serum lipids, improved hepatic steatosis-related morphology and enhanced hepatic antioxidant status. SCPs were also associated with improved intestinal morphology, increased mucin-associated staining, decreased serum diamine oxidase levels and reduced hepatic lipopolysaccharide accumulation. 16S rRNA sequencing showed SCP-associated microbial shifts, with correlations linking taxa to metabolic and barrier markers. Fermentation products generated in the presence of digested SCPs improved oxidative-stress and MUC2-related readouts in LS174T cells. Conclusions: During diet normalization, SCPs were associated with additional improvements in adiposity, lipid profiles, hepatic antioxidant status, intestinal barrier readouts, and gut microbiota. These findings support further investigation of SCPs as standardized marine protein hydrolysates, but active components, causal mechanisms, long-term efficacy, safety, and human relevance remain to be established. Full article

Diabetes mellitus represents a major global health challenge with rapidly increasing prevalence and substantial morbidity driven by metabolic and vascular complications. Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and are increasingly implicated in the pathogenesis and progression of diabetes. This review summarizes current knowledge on EV biology, including their classification, cellular sources, biogenesis, uptake mechanisms, and molecular cargo. We discuss the contribution of EV-associated microRNAs to immune dysregulation and β-cell damage in type 1 diabetes mellitus (T1DM), as well as the role of EVs in insulin resistance, metabolic signaling, and vascular dysfunction in type 2 diabetes mellitus (T2DM). Particular emphasis is placed on EV-mediated modulation of endothelial function, angiogenesis, and tissue repair, alongside their involvement in the impairment of insulin receptor integrity. We further explore how lifestyle factors may influence EV composition and function, highlighting their potential integration into preventive strategies. Finally, we evaluate the emerging therapeutic potential of EVs as biomarkers and delivery systems, while addressing current limitations and future directions. Collectively, EVs represent a promising frontier in understanding diabetes pathophysiology and developing innovative diagnostic and therapeutic approaches. Unlike previous reviews that examine EVs separately as biomarkers or therapeutic vehicles, this review integrates emerging evidence supporting EVs as mediators of systemic communication linking pancreatic islets, adipose tissue, immune cells, vascular endothelium, kidney, heart, and retina throughout diabetes progression. We further critically evaluate translational barriers that currently limit clinical implementation of EV-based diagnostics and therapeutics. Full article

Inflammaging is defined as chronic low-grade inflammation associated with aging and is increasingly recognized as a dynamic and mechanistically driven biological process rather than a state adequately described by circulating biomarkers alone. Traditional inflammatory markers alone, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive Protein (CRP), fail to capture the complexity, tissue specificity, and causal architecture of inflammaging. Recent experimental evidence has demonstrated that diverse upstream drivers, including immunosenescence, gut microbiome dysbiosis, metabolic dysfunction, and cellular senescence, converge on a limited number of central inflammatory hubs, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, GMP–AMP synthase–stimulator of interferon genes (cGAS–STING), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and p38 mitogen-activated protein kinase (p38 MAPK) signaling. These mechanistic nodes represent promising therapeutic targets, potentially modifiable biological processes, and support the emerging concept of ‘druggable inflammaging’, whereby senotherapeutics, inflammasome inhibitors, innate immune modulators, and metabolic interventions may actively modify aging-associated inflammatory biology rather than simply monitor it through biomarkers. This review highlights a paradigm shift from biomarker-based assessment toward mechanism-based intervention, where inflammaging can be characterized as a modifiable biological process and a central target for precision pharmacological strategies in aging-related diseases. Full article

Selenium (Se) is an essential micronutrient required for redox regulation and metabolic homeostasis. Altered biomarkers of Se status have been linked with obesity and metabolic syndrome, yet its role in these conditions, particularly in a sex-specific context, is not well defined. This study investigated the impact of suboptimal Se intake on metabolic risk profiles in male and female mice with pre-existing diet-induced obesity. C57BL/6N mice were fed either a standard diet with adequate Se (SD-ASe), a Western diet with adequate Se (WD-ASe), or WD-ASe followed by a Western diet containing suboptimal Se levels (WD-SOSe). Metabolic parameters, adipokine profiles, tissue Se distribution, and gene expression in visceral white adipose tissue (vWAT) were assessed. Both sexes exhibited increased weight gain and adiposity in response to a Western diet; however, only males developed hypertension and elevated non-fasted blood glucose levels. Suboptimal Se intake elicited marked sex-dependent effects. In females, it induced elevated non-fasted blood glucose levels and circulating leptin, and further dysregulated circulating adipokine profiles, accompanied by pronounced alterations in selenoprotein expression and redox-related pathways in vWAT. In contrast, male mice exhibited a partial adaptation, including reduced glucose levels and minimal alterations in gene expression. Tissue Se distribution also appeared to be influenced by biological sex. These findings demonstrate that suboptimal Se intake may exacerbate obesity-related metabolic dysfunction in a sex-specific manner, with females showing greater susceptibility, underscoring the importance of micronutrient status and sex differences in metabolic disorders. Full article

Critically ill obese patients with gynecological cancer represent a high-risk population with complex nutritional needs. Although excess adiposity may suggest adequate energy reserves, it often conceals sarcopenia, micronutrient deficiencies, and functional malnutrition, contributing to impaired wound healing, immune dysfunction, prolonged mechanical ventilation, increased susceptibility to infections, and adverse oncologic outcomes. Obesity-associated inflammation, insulin resistance, and tumor-driven catabolism further exacerbate metabolic stress and complicate nutritional management in the intensive care setting. Accurate nutritional assessment requires a multimodal approach incorporating body composition analysis, functional measures, and laboratory parameters, as conventional indices such as body mass index may underestimate nutritional risk. Nutritional support should be individualized and may include early enteral nutrition to preserve gut integrity, supplemental or total parenteral nutrition when gastrointestinal function is compromised, high-protein regimens, and targeted micronutrient replacement. Immunonutrition, including arginine, glutamine, omega-3 fatty acids, and nucleotides, has emerged as a promising strategy to modulate inflammation, enhance immune function, and support tissue repair. This narrative review summarizes current evidence regarding obesity-related metabolic dysfunction, nutritional assessment, enteral and parenteral nutrition, and immunonutrition in obese critically ill patients with gynecological cancer. It highlights the challenges associated with sarcopenic obesity and hidden malnutrition while providing a clinically relevant overview for intensivists, gynecologic oncologists, surgeons, and nutrition specialists. Early recognition of nutritional risk and implementation of individualized multimodal nutritional strategies may improve recovery and clinical outcomes. However, high-quality ICU-specific studies remain limited, and further prospective research is needed to establish evidence-based nutritional protocols and evaluate their impact on survival, treatment tolerance, and quality of life in this vulnerable population. Full article

Lipedema is a chronic adipose tissue disorder characterized by disproportionate and often painful enlargement of the extremities, occurring predominantly in women. Despite increasing clinical recognition, the underlying pathophysiology remains incompletely understood and is likely multifactorial. Existing evidence suggests contributions from vascular alterations, adipose tissue remodeling, inflammatory activation, hormonal influences, and lymphatic dysfunction. This review proposes a hypothesis-generating integrative framework in which lipedema may reflect a regenerative imbalance of subcutaneous adipose tissue. Within this model, genetically and hormonally modulated endothelial permeability could promote activation of perivascular adipose-derived stromal/stem-cell niches and stromal vascular fraction signaling pathways, thereby facilitating coupled angiogenesis and adipogenesis. Progressive adipocyte hyperplasia and hypertrophy may subsequently contribute to inflammatory remodeling, pain generation, and secondary impairment of dermal and subdermal lymphatic drainage. The proposed framework attempts to integrate clinical, histological, imaging, molecular, and endocrine observations into a biologically coherent conceptual model. At the same time, the review emphasizes the current limitations of the available evidence, the heterogeneity of lipedema phenotypes, and the ongoing controversies regarding disease progression, obesity overlap, and the relative role of lymphatic dysfunction. Finally, the potential mechanistic rationale of lymphatic-sparing liposuction is discussed in the context of tissue decompression, restoration of lymphatic transport, and interruption of persistent adipose remodeling. The model presented here should be interpreted as a hypothesis-generating conceptual scaffold requiring prospective validation. Importantly, the present framework should be interpreted as a biologically plausible and hypothesis-generating conceptual model rather than a definitive mechanistic doctrine. Several proposed interactions remain associative and require prospective biological validation. Full article

Alzheimer’s disease (AD) and metabolic syndrome often occur together, sharing characteristics such as insulin resistance, dyslipidemia, and chronic inflammation. Metabolic dysfunction frequently precedes cognitive decline, indicating that early intervention might alter the disease’s progression. We investigated whether the GLP-1 receptor agonist semaglutide (SMGL) influences metabolic impairment and AD pathology in an AD mouse model. Male and female 5xFAD and wild-type (WT) mice on regular (RD) or high-fat diets (HFD) were administered SMGL for 13 weeks. SMGL-treated groups exhibited significant, context-dependent effects. In metabolically challenged 5xFAD HFD mice, treatment led to reduced body weight, improved glucose tolerance, normalized cholesterol levels, and a restored balance of adiponectin and leptin. These improvements were associated with reduced Aβ40 and Aβ42 levels, restored GLP-1 receptor expression, increased synaptophysin and βIII-tubulin levels, and enhanced spatial memory. SMGL also decreased Iba1 and CD68 immunoreactivity in the hippocampus and cortex, reduced macrophage infiltration, and lowered CD36 expression in visceral adipose tissue (VAT), indicating coordinated anti-inflammatory effects. WT RD mice showed minimal metabolic responses and a modest decline in Y-maze performance, suggesting that excessive GLP-1 receptor activation may disrupt neuronal homeostasis when metabolic status is normal. SMGL acts as a context-specific metabolic and neuroprotective agent, offering the greatest benefits under conditions of metabolic dysfunction. These findings in a preclinical model suggest that targeting early metabolic disturbances provides a testable hypothesis for attenuating AD-related neurodegeneration, though further translational studies are required. Full article