Search Results (7,024)

In hemodialysis patients, Body Mass Index is insufficient in assessing their nutritional status due to the ‘obesity paradox’ and the association between body composition and inflammation. This study assessed the relationship between body composition, traditional inflammatory markers, the new NETosis indicators (neutrophil extracellular traps), and their association with 12-month mortality. The study included 99 maintenance hemodialysis (HD) patients. Their body composition was assessed using bioelectrical impedance analysis. Blood serum was tested for inflammatory markers (hs-CRP-high sensitive c-reactive protein, IL-6 interleukin-6, TNF-α tumor necrosis factor alfa, IL-1β interleukin-1 beta), NETosis markers (citrullinated histone CH3, myeloperoxidase -MPO, elastase), and nutritional status parameters (albumin, transferrin). No correlation between BMI -body mas index and inflammation was demonstrated. Higher adipose tissue, particularly visceral, was significantly positively correlated with IL-6 and hs-CRP levels, while muscle mass was negatively correlated with inflammation. Dialysis catheter use was associated with higher CH3 levels (NETosis indicator) and lower albumin concentrations. Low albumin levels and high TNF-α levels were independent predictors of death. Body composition, rather than BMI, is associated with the severity of inflammation. Visceral obesity is positively correlated with increased inflammation, while muscle mass shows an inverse association. Dialysis catheters are linked to higher NETosis markers and lower albumin levels, which are associated with a poorer prognosis. Full article

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into different cellular lineages, including adipocytes, chondrocytes, and osteocytes. This makes them strong candidates for repairing degenerative joint conditions such as osteoarthritis, in which native cartilage lacks repair capacity. The synovium is an attractive MSC source, with synovial MSCs demonstrating superior chondrogenic and proliferative potential compared to those from bone marrow or adipose tissue. The synovial joint is a heterogeneous environment, and MSCs can be isolated from the membrane, fluid, different histological subtypes of fibrous and adipose synovium, and different anatomical regions of synovium. This systematic review assesses whether MSCs from different synovial sources possess distinct properties. 2312 papers were identified, of which 10 met the inclusion and exclusion criteria and were included in the final review. Significant differences were identified in proliferation characteristics, immunophenotype and differentiation potential. Proximity to vasculature appeared to correlate with proliferation and differentiation potential, and MSCs from the synovial membrane may have superior proliferative characteristics compared to those from synovial fluid. More work is required to fully characterise these differences and understand their underlying molecular bases, but these findings may help inform the choice of MSC source for regenerative therapies. Full article

A fraction of the insulin-stimulated uptake of long-chain fatty acids (FAs) is mediated by the FA translocase cluster of differentiation 36 (CD36) in white adipocytes. Intracellular vesicle-localized CD36 is redistributed to the plasma membrane following insulin stimulation, enhancing the uptake of long-chain FAs across the plasma membrane. We previously developed an epitope-tagged CD36 reporter, which enabled the visualization and quantification of the plasma membrane translocation of CD36. Herein, we demonstrate that the insulin-stimulated CD36 translocation is regulated by the phosphoinositide 3-kinase (PI3K)/Akt2/Rac1/RalA axis in adipocytes of subcutaneous white adipose tissue (WAT) in living mice. The uptake of long-chain FAs by insulin was completely abrogated in white adipocytes isolated from adipocyte-specific rac1-knockout (adipo-rac1-KO) mice. Correspondingly, the translocation of CD36 to the plasma membrane by insulin was also totally inhibited in Rac1-deficient white adipocytes. PI3K and Akt2 acted upstream of Rac1, and the guanin nucleotide exchange factor FLJ00068 served as a regulator for Rac1. Furthermore, the involvement of another small GTPase RalA was suggested by inhibitory effects of a dominant-negative mutant. Taken together, these results support the notion that insulin regulates the plasma membrane translocation of CD36 by mechanisms similar to those for the translocation of the glucose transporter GLUT4 in white adipocytes. Full article

Osteoarthritis (OA) causes chronic pain and impaired mobility in dogs. Since current therapies cannot restore damaged articular cartilage, tissue engineering approaches offer promising therapeutic strategies. This study aimed to investigate whether peri-ovarian adipose tissue (POAT) represents a biologically competent and functionally relevant alternative source of mesenchymal stromal cells (MSCs) compared to subcutaneous adipose tissue (SAT). Samples were collected from five healthy and normal-weight Labrador Retrievers undergoing routine ovariectomy. MSCs were characterized according to the International Society for Cellular Therapy, including doubling time, growth curves, colony-forming unit assays, immunophenotyping, and trilineage differentiation potential. Chondrogenic differentiation was assessed through Alcian Blue staining and qPCR analysis of COL2A1, COL1A1, COL10A1, and SOX9 expression at multiple timepoints. MSCs derived from both adipose depots showed comparable mesenchymal characteristics, proliferative capacity, immunophenotypic profiles, and multilineage differentiation potential. POAT-MSCs exhibited enhanced chondrogenic differentiation compared to SAT-MSCs, with stronger extracellular matrix deposition and significantly increased COL2A1 expression at later stages of differentiation than SAT-MSCs. SOX9 expression supported a more advanced chondrogenic commitment in POAT-derived cells, while COL10A1 expression remained low and stable in both groups. These preliminary findings suggest that POAT, routinely discarded after ovariectomy, may represent a promising and ethically advantageous source of canine MSCs for regenerative medicine. 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

Objectives: Explore and compare the effects of 8-week time-restricted eating (TRE), walking exercise, and their combination on fat and lean muscle distribution in female college students with hidden obesity. Methods: A total of 68 participants were randomly assigned to four groups: Control (CON), TRE, Exercise (EXE), and TRE + EXE. An 8-week intervention was begun according to a predetermined experimental plan, comparing changes in body fat and lean tissue indices before and after the intervention. Results: Before and after the intervention, the TRE group showed a significant decrease in body mass, body mass index (BMI), and total lean mass (p < 0.05). The EXE group saw a significant reduction in visceral fat area, visceral fat mass, and visceral fat volume (p < 0.01). The TRE + EXE group experienced a significant decrease in android lean mass (p < 0.05); Comparing before and after the intervention, there were no statistically significant differences in the body fat percentage, total fat mass, fat and lean in the android and gynoid areas, and %fat in trunk/%fat in legs among the CON, TRE, EXE, and TRE + EXE groups (p > 0.05). After the intervention, there were no significant differences in the body fat percentage, total fat mass, total lean mass, fat and lean in the android and gynoid areas, %fat in trunk/%fat in legs, visceral fat area, visceral fat mass, visceral fat volume, subcutaneous fat area, subcutaneous fat mass, and subcutaneous fat volume among the four groups (p > 0.05). Conclusions: An 8-week TRE intervention in young women with hidden obesity reduced body mass and BMI but also decreased total lean mass, potentially compromising metabolic health, with no statistically significant changes in total body fat or regional fat distribution. Walking exercise showed significant reductions in visceral adiposity indicators (VFA, VFM, VFV), whereas the combined TRE + EXE group did not achieve comparable reductions. These findings suggest that while isolated TRE facilitates body mass loss, it carries a distinct risk of muscle tissue loss and may not confer comparable benefits on visceral fat reduction as walking exercise. However, the generalizability of these preliminary observations is constrained by methodological limitations including retrospective registration, participant attrition, and restricted statistical power. Consequently, these exploratory outcomes must be interpreted with caution, warranting future robust, large-scale trials with enhanced compliance monitoring to optimize prescriptive guidelines for this specific cohort. Full article

In addition to its role in energy storage, adipose tissue contributes substantially to energy metabolism, endocrine regulation, and inflammatory processes. Sujiang pigs, a hybrid breed approved by the National Livestock and Poultry Genetic Resources Committee of China as a new national breed in 2013, possess a genetic predisposition for substantial fat deposition, making them an ideal model for investigating the mechanisms underlying adipose tissue accumulation. In this study, back fat (BF; subcutaneous adipose tissue), greater omentum (GOM; visceral adipose tissue), and mesenteric adipose tissue (MAD; visceral adipose tissue) were collected from three 6-month-old male Sujiang pigs for RNA-seq analysis. Comparative analyses identified 3005 differentially expressed genes (DEGs) between BF and GOM, 975 DEGs between BF and MAD, and 892 DEGs between GOM and MAD. To validate the reliability of the sequencing data, five DEGs were randomly selected for RT-qPCR verification. The DEGs were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. By integrating protein–protein interaction (PPI) networks with bioinformatics analyses, we identified candidate genes potentially associated with lipid metabolism (e.g., WNT9A, WNT5A, and PDGFRA) and inflammatory responses in adipose tissue (e.g., CSF1R, C1QB, and CD4). These findings indicate potential molecular differences between porcine visceral and subcutaneous adipose tissues and may serve as a reference for further studies on the molecular regulation of adipose tissue metabolism. Full article

Background/Objectives: Gender-affirming hormone therapy (GAHT) is associated with clinically relevant changes in body composition, energy metabolism, and functional capacity in transgender and gender-diverse individuals. The nutritional implications of these adaptations remain insufficiently characterized, and current assessment models, largely derived from cisgender populations, may not fully capture hormone-related body composition and metabolic changes. This narrative review aims to synthesize the metabolic and body composition effects of GAHT, evaluate methodological limitations in assessing nutritional status, and propose an integrated framework for clinical nutritional management. Methods: A narrative literature review was conducted through searches of PubMed/MEDLINE, Scopus, and Web of Science, complemented by screening of relevant guidelines and reference lists. Priority was given to longitudinal studies, mechanistic studies, systematic reviews, meta-analyses, and clinical guidance addressing GAHT-related changes in body composition, metabolism, nutritional status, and functional outcomes. Results: Available evidence suggests that GAHT is associated with sex steroid-related, tissue-specific changes in body composition and metabolism. In transgender men, testosterone is generally associated with increases in lean body mass (LBM), reductions in fat mass, and potential increases in visceral adiposity, alongside possible increases in energy expenditure and altered cardiometabolic profiles. In transgender women, estrogen therapy, combined with androgen suppression, is generally associated with reductions in LBM and redistribution of subcutaneous fat, with heterogeneous metabolic and functional responses. Across both groups, changes in body composition are not consistently reflected by the Body Mass Index or functional outcomes, suggesting a possible dissociation between structural and functional adaptation. Common assessment tools show limitations, including reliance on cisgender-derived reference standards and inability to capture dynamic hormonal transitions. Conclusions: Current evidence supports the need for a longitudinal and individualized interpretation of nutritional and body composition changes during GAHT. A shift toward longitudinal, multimodal nutritional assessment, integrating body composition, functional measures, biochemical markers, dietary intake, and clinical context, may improve clinical monitoring and reduce misclassification. 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

Background: Obesity is an independent and major risk factor for cardiovascular diseases. However, the presence of common comorbidities such as diabetes and hypertension makes it difficult to understand the direct impact of obesity on the myocardium. The aim of this study is to evaluate the isolated effects of weight loss achieved after bariatric surgery on left ventricular (LV) geometry and diastolic functions in individuals with the “Metabolically Healthy Obese” (MHO) phenotype. Materials and Methods: The study included 28 patients (Surgical Group) who underwent Laparoscopic Sleeve Gastrectomy (LSG) between January 2022 and December 2025, had a preoperative Body Mass Index (BMI) > 40 kg/m², and had no known cardiovascular or metabolic diseases. The control group consisted of 25 age- and gender-matched metabolically healthy morbidly obese patients who had not undergone surgery. Demographic and echocardiographic data of all participants were analyzed at baseline and at 6 months. Results: Weight Loss: In the surgical group, BMI decreased from 46.21 kg/m² to 37.11 kg/m² at the 6th month, while no significant change was observed in the control group. Cardiac Structure: In the surgical group, Left Ventricular Mass Index was significantly decreased from 51.11 g/m² to 44.57 g/m². Cardiac Function: The E/A ratio, an indicator of diastolic function, increased significantly from 1.19 to 1.34 in the surgical group, indicating notable improvement. No clinically meaningful change in systolic function was detected. Metabolic Parameters: The surgical group exhibited marked improvements in glucose and lipid profiles (decrease in Total Cholesterol, increase in HDL). Conclusions: The study demonstrates that bariatric surgery, independent of metabolic comorbidities, directly provides “reverse remodeling” of cardiac structure and improves function through reduction of adipose tissue and alleviation of hemodynamic load. These results support the effectiveness of surgery in reducing cardiovascular risk and preserving cardiac structure even in morbidly obese patients without comorbidities. Full article

Background/Objectives: Mesenchymal stem cells (MSCs), due to their regenerative and multipotent properties, have emerged as promising therapeutic agents in tissue repair and regeneration. These biological characteristics might contribute to optimized anastomotic healing and to a reduction in postoperative complications following digestive surgery. The present study aimed to evaluate whether intraperitoneal or perianastomotic administration of MSCs provides superior healing outcomes in colonic anastomoses in Wistar rats. Methods: MSCs were isolated from inguinal adipose tissue harvested from 2 Wistar rats. Thirty male Wistar rats were allocated to 3 groups: (i) the control group, with regular anastomosis, (ii) peri-anastomotic injection of MSCs, and (iii) intraperitoneal injection of MSCs. The animals were sacrificed on postoperative day 14. The evaluated outcomes included clinical evolution, adhesion index, histological characteristics, and tissue hydroxyproline content. Results: The incidence of anastomotic leakage and the mortality rate were 0%. Therefore, the present study primarily demonstrates changes in surrogate markers of healing, including inflammatory response, collagen deposition, adhesion formation, and hydroxyproline content. The adhesion index was similar in the groups receiving MSC administration (p = 0.05); however, intraperitoneal administration demonstrated superior outcomes when compared to standard anastomosis in reducing adhesion formation (p = 0.002). Histopathological analysis showed a decreased inflammatory process and an increased collagen deposition at the anastomotic site following MSC administration (p < 0.05). Moreover, tissue hydroxyproline levels were significantly increased after both perianastomotic (0.831 ± 0.02, p < 0.05) and intraperitoneal (0.54 ± 0.02, p < 0.05) MSC administration compared with the control group (0.251 ± 0.006). Conclusions: These results suggest that MSC administration may improve histological and biochemical markers associated with colonic anastomotic healing in a non-ischemic experimental model. The experimental model used is suitable for further studies aimed at determining the optimal indications, routes of administration, and adjunctive agents that may potentiate the effects of MSCs. Full article

Adipose tissue expansion in obesity is accompanied by extracellular matrix (ECM) remodeling, regulated by matrix metalloproteinases (MMPs). Visceral adipose tissue (VAT) is metabolically more active than subcutaneous adipose tissue (SAT). However, depot-specific differences in proteolytic activity and protein glycooxidation remain incompletely characterized. In this case–control study, we assessed the activity of six matrix metalloproteinases (MMP-1, -2, -7, -9, -11, and -13) using a fluorescence resonance energy transfer (FRET) assay and quantified advanced glycation- and glycooxidation-related markers in paired VAT, SAT, and plasma samples obtained from 40 patients with obesity and 21 non-obese controls. The activities of all assessed MMPs were greater in patients with obesity than in the control group (p < 0.01 for all MMPs). Direct tissue-compartment comparisons showed that MMP activity and glycooxidation-related markers were most pronounced in VAT, with markedly higher values in obese individuals compared with controls. In VAT of obese individuals, median MMP activity was approximately 50–60% higher compared with controls. Amyloid cross-β-structure, vesperlysine, and pentosidine were significantly elevated in VAT in obesity, whereas plasma levels were markedly lower and showed limited group differences. No significant differences were observed between obese participants with and without metabolic syndrome. Obesity is associated with a depot-specific molecular profile characterized by enhanced proteolytic and glycooxidative activity predominantly within visceral adipose tissue. These findings highlight the importance of tissue-compartment-specific assessment in obesity. Full article

Succinate, a tricarboxylic acid (TCA) cycle intermediate, is the essential signal molecule that links metabolic signals and inflammation. Dietary succinate supplementation has been reported to prevent obesity induced by a high-fat diet (HFD). However, the underlying mechanism remains elusive. Here, we found that dietary succinate elevated the serum succinate levels. Meanwhile, we found succinate increased methyltransferaselike 3 (METTL3) protein expression in brown adipocytes, thereby elevating N⁶-methyladenosine (m⁶A) levels in Hypoxia-inducible factor1-alpha (Hif1a) mRNA. Hif1a mRNA is recognized by the m⁶A-binding protein YTH domain-containing family protein 1 (YTHDF1), facilitating HIF1A protein expression. HIF1A activates the transcription of thermogenic genes, ultimately increasing brown adipose energy expenditure. Together, our research provided new insights into the effect of succinate on m⁶A modification in brown adipose tissue thermogenesis. 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

Liver fibrosis is a severe but common disease without an easy-to-access option for efficient treatment. Mesenchymal stem cells (MSCs) of different origins have been tested for antifibrotic effects in vitro, in vivo, and in clinical studies over the two last decades, although the comparative efficiency of different subtypes remains not fully understood, especially for long-term survival. In this study, we aimed to compare the long-time persistence of favorable effects in male Wistar rats with liver fibrosis treated using MSCs derived from white adipose tissue (AdMSCs) and bone marrow (BMSCs). Liver fibrosis was induced by carbon tetrachloride. We studied the survival rate; oxidative index, assessed via laser Doppler flowmetry; hepatic markers in blood plasma—albumin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; the ratio of liver to body mass; histological parameters—the number of adipocytes, lymphocytes, siderophages, and Ki67⁺ cells; and the relative areas of connective tissue proper and reticular fibers. Extra mortality was only typical for fibrotic animals subjected to the sham treatment in the first two weeks. Up to Day 270 of this study, both MSC-treated groups showed barely any differences from animals undergoing the sham treatment in terms of the oxidative index and blood markers, although AdMSC-treated rats presented a more favorable histological pattern than BMSC-treated ones, considering the relative area of reticular fibers and the Ki67 cell count. This study suggests that AdMSC treatments may be more appropriate than BMSC treatments in animal liver fibrosis models, with the results showing better potential for liver tissue regeneration 9 months after treatment. Full article