Search Results (3,039)

Background: Continuous-flow left ventricular assist devices (LVADs) and heart transplantation (HTX) improve survival and quality of life in advanced heart failure. However, restoration of central hemodynamics does not consistently normalize exercise capacity, physical performance, or body composition. Persistent skeletal muscle dysfunction, endothelial abnormalities, metabolic disturbances, and adverse body composition changes frequently limit functional recovery. Methods: This narrative review examines determinants of rehabilitation outcomes across the transition from advanced heart failure to LVAD support and subsequent HTX. Particular emphasis is placed on restoration of pulsatile circulation, vascular and microcirculatory adaptation, immunosuppressive therapy, body composition remodeling, and emerging immunometabolic mechanisms. Results: Rehabilitation outcomes appear to be increasingly determined by peripheral rather than central cardiovascular factors. Continuous-flow LVAD support induces vascular, endothelial, autonomic, and microcirculatory adaptations that may persist after transplantation. Although HTX restores physiological pulsatile circulation and cardiac output, recovery is often limited by skeletal muscle dysfunction, impaired mitochondrial capacity, chronotropic abnormalities, and adverse body composition changes. Immunosuppressive therapies further influence muscle plasticity, adipose tissue distribution, insulin sensitivity, endothelial function, and exercise adaptation, contributing to phenotypes such as sarcopenia, myosteatosis, and sarcopenic obesity. Conclusions: Functional recovery after LVAD support and HTX is a multidimensional process extending beyond restoration of cardiac function. We propose a hemodynamic–immunometabolic framework in which vascular adaptation, skeletal muscle biology, body composition remodeling, and immunosuppressive therapy interact to determine rehabilitation success and may inform personalized rehabilitation strategies. Full article

Objectives: Obesity disrupts adipose and systemic immune–metabolic homeostasis, yet the molecular mechanisms through which exercise restores abnormal tissue function remain incompletely defined. This study aimed to screen cross-tissue candidate genes associated with exercise-mediated correction of obesity-related transcriptional disorders via multi-tissue transcriptome profiling and bioinformatic gene prioritization. Methods: Transcriptomic datasets of mouse visceral white adipose, subcutaneous white adipose and skeletal muscle were downloaded from the public GEO database, covering normal control, high-fat induced obese and post-exercise intervention groups. R programming was applied to complete differential analysis, GO/KEGG enrichment, PPI network, LASSO and GSEA; independent human adipose datasets from GEO validated candidate genes. Results: Exercise reversed obesity-triggered transcriptional changes in adipose tissues. Exercise-responsive genes concentrated on immune inflammation, lipid and energy metabolism. Key hub genes for tissue remodeling were screened, and depot-specific pathway regulation was verified by GSEA. CCL2 showed consistent expression trends across mouse and human adipose data. Conclusions: This study identifies distinct tissue-specific transcriptional responses to exercise: visceral adipose mainly achieves reversal of obesity-induced inflammatory dysregulation, subcutaneous adipose undergoes combined immune–inflammatory and metabolic reprogramming, while skeletal muscle presents only energy-metabolism adaptive remodeling without obvious reversal of obese gene disorders. Immune–metabolic pathways dominate exercise-induced restoration in adipose tissues. Integrated network screening and cross-species validation identified CCL2 as a conserved candidate associated with exercise-responsive immune–metabolic pathways, providing valuable molecular candidates for further anti-obesity research. Full article

The Developmental Origins of Health and Disease framework proposes that environmental exposures during critical periods of development can shape physiological systems and influence the risk of chronic diseases later in life, including diabetes and metabolic syndrome. Most research on metabolic programming has focused on classical metabolic organs such as the liver, pancreas, and adipose tissue. However, skeletal muscle plays a central role in systemic glucose homeostasis and metabolic flexibility, accounting for the majority of insulin-stimulated glucose uptake in the body. Because muscle metabolism is closely regulated by neural activity through the organisation of motor units, the development of the motor neuromuscular axis may represent an underexplored dimension of metabolic programming. This review examines evidence linking early-life metabolic environments to neuromuscular development and discusses how alterations in the maturation of motor neurons, neuromuscular junctions, and muscle fibre phenotype may influence long-term metabolic outcomes. Evidence from epidemiological studies, experimental models, and mechanistic research suggests that maternal metabolic disturbances, including hyperglycaemia, obesity, and systemic inflammation, can influence foetal development through metabolic and inflammatory pathways affecting both neural and muscular components of the motor system. These findings support the hypothesis that the motor neuromuscular axis may represent a structural interface linking early developmental exposures to long-term metabolic regulation and risk of metabolic syndrome. Full article

Melanoma remains a major global health burden, though immunotherapy and targeted therapy have markedly improved survival. Obesity has paradoxically been associated with favorable outcomes in melanoma, yet body mass index (BMI) alone fails to capture its influence on treatment response. To address this gap, we conducted a multi-site cohort study within the Canadian Melanoma Research Network, including patients with advanced melanoma treated with immunotherapy or targeted therapy. Body composition was quantified using computerized tomography (CT) imaging to assess visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM) mass and intermuscular adipose tissue (IMAT), and associations with progression-free survival (PFS) and overall survival (OS) were evaluated. No overall association was seen for BMI, SAT, VAT, IMAT or SM with PFS or OS. In the targeted therapy subset, higher BMI, SAT, VAT and SM were associated with better OS (hazard ratios 0.56 to 0.65), while no effect was seen in the immunotherapy group. IMAT emerged as a novel prognostic marker, with elevated levels associated with lower OS in males and better OS in females. Our findings show that CT-based body composition is not associated with survival outcomes in patients with advanced melanoma receiving immunotherapy. Full article

Background: Obesity is a multifactorial metabolic disorder characterized by excessive adiposity, chronic low-grade inflammation, and dysregulated incretin and energy-sensing pathways, including glucagon-like peptide-1 (GLP-1) and AMP-activated protein kinase (AMPK). Methods: This in vitro and in vivo study evaluated the potential of select phytochemical candidates and botanical formulations to stimulate GLP-1 secretion and activate AMPK signaling. Results: Fourteen phytochemicals and six combinations were screened in human NCI-H716 enteroendocrine cells at 10–20 µg/mL to assess cytotoxicity and GLP-1 secretion. In human adipocytes, selected combinations reduced lipid accumulation and monocyte chemoattractant protein-1 (MCP-1) secretion. Among the tested formulations, combination #4, consisting of ginseng root extract, curcumin, white kidney bean extract, fenugreek extract, capsaicin, and bitter melon extract, significantly increased phosphorylated AMPK levels in vitro. In high-fat diet-induced obese mice, oral administration of combination 4 reduced body weight gain and white adipose tissue mass, improved metabolic biochemical parameters, restored leptin and MCP-1 levels toward normal values, increased GLP-1 level, and normalized GLP-1 receptor expression in subcutaneous adipose tissue. Conclusions: These preclinical findings demonstrate that this multi-component botanical formulation modulates GLP-1 secretion, AMPK phosphorylation, lipid accumulation, and inflammatory markers in cellular and murine models. These data provide a foundational rationale for its further evaluation as a non-toxic candidate for metabolic management. Full article

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 exhibits pronounced sex-dependent differences in susceptibility and progression; however, the molecular mechanisms coordinating central energy sensing with peripheral thermogenic responses remain incompletely defined. Selenoprotein F (SELENOF), an endoplasmic reticulum (ER)-resident member of the selenoprotein family involved in protein quality control and redox-sensitive metabolic regulation, has not previously been investigated in the context of diet-induced obesity. In the present study, WT and SELENOF-deficient mice subjected to a 16-week high-fat diet (HFD) were combined with primary brown adipocyte experiments to determine the role of SELENOF in systemic metabolic homeostasis. SELENOF deficiency markedly aggravated HFD-induced weight gain, adipose tissue expansion, dyslipidemia, and hyperleptinemia selectively in female mice, whereas no genotype-dependent effects were observed in males. Mechanistically, SELENOF deficiency intensified hypothalamic ER stress and leptin resistance, as reflected by increased GRP78, p-IRE1α, and p-PERK expression together with SOCS3 upregulation, reduced STAT3 phosphorylation, and activation of the IKK/NF-κB inflammatory pathway. In parallel, SELENOF deficiency reduced circulating free triiodothyronine (FT₃) levels and the ratio of free triiodothyronine to free thyroxine (FT₃/FT₄ ratio), and suppressed DIO2 and UCP1 expression in brown adipose tissue (BAT). Experiments in primary brown adipocytes further showed that SELENOF deficiency did not disrupt proximal β3-adrenergic signaling but attenuated the downstream induction of DIO2 and UCP1. Collectively, these findings provide preliminary evidence that SELENOF is associated with sex-dependent metabolic adaptation during HFD-induced stress by linking hypothalamic proteostasis with the thyroid hormone-related thermogenic signaling program in BAT. Full article

The global prevalence of type 2 diabetes continues to rise at an alarming pace, challenging existing strategies for disease prevention and management. Beyond traditional risk factors, increasing evidence indicates that glucose metabolism is temporally regulated by the body’s 24 h biological clock and oscillates based on the time of day. Disturbances of the circadian clock function are linked to impairments in glucose homeostasis and increased risk of obesity and diabetes. This review explores the intricate relationship between the circadian system and glucose homeostatic control. We begin with an introduction to the hierarchical organization of the circadian system. Next, we examine the role of the circadian clock in regulating organs and tissues that are involved in glucose metabolism, i.e., the pancreas, skeletal muscles, the liver and adipose tissue. We next review evidence that supports the involvement of circadian disturbances in the pathogenesis of diabetes. Finally, we discuss chronotherapy and its potential application in clinical intervention of diabetes. As type 2 diabetes becomes increasingly common worldwide, understanding how the body’s internal clock shapes this disease may open new and powerful opportunities for its prevention and treatment. Full article

While medium-chain triglycerides (MCTs), medium- and long-chain triglycerides (MLCTs), and carotenoids individually possess anti-obesity properties, the synergistic metabolic regulatory effects of their combined intervention remain under-investigated. This study explored the effects of MCTs or structured MLCTs combined with natural carotenoids on high-fat diet (HFD)-induced obese mice. After establishing obesity in C57BL/6J mice using a 60% HFD, a ten-week intervention was conducted using 45% HFD containing 150 mg/kg carotenoids across three groups: MCT-C, MLCT-C, and a physical mixture of MCTs and long-chain triglycerides plus carotenoids (MCT+LCT-C), alongside a low-fat diet (LFD) control. Results showed that among the three HFD-fed intervention groups, the MCT-C group had the lowest body weight with significantly lower fat mass, fat pad coefficient, and adipocyte area, but higher liver coefficient and serum alanine aminotransferase levels compared to the LFD control group (p < 0.05). The MLCT-C and MCT+LCT-C groups exhibited higher body weight, white adipose tissue expansion, and adipocyte hypertrophy, with MCT+LCT-C showing the largest adipocyte volume and uniquely presenting hepatocyte necrosis, unlike other groups. Serum total cholesterol was lowest in MCT-C, while high-density lipoprotein cholesterol increased in MLCT-C and MCT+LCT-C. Notably, compared with the MCT+LCT-C group, MLCT-C demonstrated distinctly superior capabilities in maintaining gut microbiota homeostasis, as evidenced by enhanced community alpha diversity and significantly reduced the abundance of harmful Pseudomonadota, while preserving a highly comparable core functional profile. Collectively, these findings confirm that lipid structure differentially shapes gut microbiota and influences energy metabolism, providing a scientific basis for precision nutrition interventions. 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

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