Search Results (339)

Background: Computed tomography (CT)-derived body composition has emerged as a promising prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). However, most previous studies have relied on baseline measurements and evaluated either resected or metastatic disease separately. We aimed to investigate the prognostic significance of both baseline and longitudinal CT-derived body composition changes in clinically distinct but therapeutically homogeneous cohorts of patients with PDAC receiving FOLFIRINOX. Methods: This retrospective single-center study included 98 consecutive patients with histologically confirmed PDAC treated with FOLFIRINOX between 2018 and 2025. Forty-seven patients underwent curative-intent resection followed by adjuvant modified FOLFIRINOX, whereas 51 patients with unresectable metastatic disease received first-line FOLFIRINOX. Skeletal muscle index (SMI) and visceral adipose tissue (VAT) were quantified on serial CT scans obtained at the third lumbar vertebral level before treatment and during therapy. Follow-up CT scans suitable for longitudinal body composition analysis were available for 46 of 51 patients (90.2%) in the metastatic cohort. Overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: Baseline CT-derived body composition parameters were not independently associated with survival in either cohort. In the resected cohort, preservation of visceral adiposity during treatment (follow-up VAT > 100 cm²) independently predicted improved OS in a multivariable model including three covariates (HR 0.460, 95% CI 0.220–0.960; p = 0.039). Median DFS and OS were 11.7 months (95% CI 6.5–16.9) and 20.9 months (95% CI 12.1–29.7), respectively. In the metastatic cohort, treatment-related skeletal muscle loss (ΔSMI) independently predicted inferior OS in a multivariable model including four covariates (HR 0.949, 95% CI 0.913–0.986; p = 0.008), while lung metastasis was also independently associated with worse survival (HR 5.792, 95% CI 1.880–17.841; p = 0.002). Median PFS and OS were 9.7 months (95% CI 8.0–11.4) and 12.7 months (95% CI 9.9–15.5), respectively. Conclusions: Longitudinal CT-derived body composition changes may provide additional prognostic information beyond baseline measurements in patients with PDAC receiving FOLFIRINOX. Preservation of visceral adiposity was associated with improved survival following curative-intent resection, whereas greater treatment-related skeletal muscle loss was associated with poorer survival in metastatic disease. These findings suggest that the prognostic relevance of body composition may vary according to disease stage and should be considered hypothesis-generating pending validation in larger prospective multicenter studies. Full article

Background: Visceral obesity is increasingly recognised not as a simple excess of adipose tissue, but as a systemic pathological condition characterised by profound metabolic, endocrine, and immune dysregulation. Visceral adipose tissue (VAT) operates as an autonomous neuro-immune-endocrine organ whose dysfunctional expansion drives insulin resistance, atherogenesis, and accelerated cellular ageing through mechanisms converging on chronic low-grade sterile inflammation, referred to as inflammaging. Objectives: This narrative review integrates evidence across four domains: (1) the multi-system clinical complications of visceral obesity and the methodological controversies surrounding its measurement; (2) the cellular heterogeneity, immunometabolic reprogramming, and molecular mechanisms through which excess VAT accelerates biological ageing, with a focus on genomic instability, mitochondrial dysfunction, the NAD⁺/sirtuin regulatory axis, cellular senescence, and inter-organ communication; (3) the role of bioelectrical impedance analysis (BIA)—particularly phase angle—as a non-invasive functional biomarker of biological age and longevity, positioned critically against alternative assessment methods; and (4) current knowledge gaps and priorities for future research. Methods: A narrative review of PubMed/MEDLINE, Google Scholar, and the Cochrane Library was conducted using MeSH terms and free-text keywords including visceral obesity, bioelectrical impedance analysis, phase angle, sarcopenia, inflammaging, mitochondrial dysfunction, cellular senescence, epigenetic clocks, NAD⁺, sirtuin, and longevity, supplemented by citation-tracking of retrieved reviews. English-language articles published up to April 2025 were considered, prioritising systematic reviews, meta-analyses, and prospective cohort studies; formal risk-of-bias tools and quantitative synthesis were not applied, consistent with a narrative review design. Results and Discussion: BIA-derived phase angle constitutes a macroscopic electrobiological correlate of inflammaging: low phase angle values in visceral obese subjects overlap with those of frail elderly individuals, reflecting impaired membrane integrity, loss of active cell mass, and altered ICW/ECW balance. However, this evidence base remains largely cross-sectional and correlative; the directionality and population-specific calibration of BIA-derived indices constitute the principal unresolved methodological questions. Integration with epigenetic clocks, circulating NAD⁺ levels, and gut microbiome indices offers a framework for dynamic biological age assessment, though prospective interventional validation is still lacking. Sarcopenic obesity, evaluated through EWGSOP2 combined with BIA-derived skeletal muscle mass index and handgrip dynamometry, represents a critical comorbidity demanding integrated therapeutic targeting. Conclusions: BIA provides a quantitative, accessible correlate for translating cellular metabolic health into clinically actionable parameters, complementary to rather than a replacement for anthropometric and imaging-based methods. Optimising phase angle and reducing VAT through anti-inflammatory nutrition, exercise, and nutraceutical strategies targeting the NAD⁺/sirtuin and mTOR/AMPK axes constitutes a measurable objective for the promotion of healthy longevity, contingent on the longitudinal, mechanistic studies identified as priorities in this review. Full article

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease and frequently improves after bariatric surgery. Conventional postoperative follow-up is mainly based on weight-loss outcomes, such as Body Mass Index (BMI), excess weight loss (EWL), total weight loss (TWL), and routine biochemical parameters, which may not fully characterize hepatic fat response. Ultrasound-derived fat fraction (UDFF) provides a quantitative non-invasive assessment of hepatic steatosis, while DXA-derived visceral adipose tissue (VAT) reflects central adiposity and metabolic risk. This study aimed to evaluate whether combined UDFF and DXA-VAT assessment provides complementary information to conventional bariatric follow-up parameters after bariatric surgery. Methods: We conducted a prospective longitudinal cohort study on 41 patients with severe obesity who underwent bariatric surgery between July 2025 and May 2026. Anthropometric, body composition, metabolic, hepatic, and biochemical parameters were assessed at baseline (T0) and 6 months postoperatively (T1). UDFF, utilizing a DAX ultrasound transducer, was used for hepatic steatosis assessment, while DXA was performed for VAT, android fat mass, total body fat percentage, and lean mass quantification. Correlation analyses, multivariable linear regression, and an exploratory clinical discordance analysis were performed. Results: At 6 months after surgery, patients showed significant improvements in body weight, visceral adiposity, insulin resistance, biochemical parameters, and hepatic steatosis. VAT reduction showed the strongest association with UDFF reduction, whereas conventional weight-loss outcomes, anthropometric, and metabolic parameters did not fully identify patients with residual steatosis. These findings suggest that hepatic fat improvement after bariatric surgery is more closely related to changes in visceral adiposity than to weight loss alone. Conclusions: Combined UDFF and DXA-derived VAT assessment may provide a practical dual-compartment imaging framework for postoperative MASLD monitoring. This approach captures both hepatic fat response and visceral adiposity remodeling, offering information that complements conventional bariatric follow-up based on weight-loss outcomes. Full article

Background: MASLD is a disorder linked to lipid metabolism and obesity, increasingly prevalent among sedentary people and leading to hepatic fibrosis. Cyclodipeptides (CDPs) have promising anti-obesogenic and liver-protective potential. Methods: CDP treatment was evaluated in a chronic MASLD model using female Wistar rats fed an obesogenic diet, with assessments of insulin resistance, glucose tolerance, liver damage, oxidative stress, and the expression of genes related to metabolic function. Results: MASLD CDP-treated rats showed low visceral adipose tissue (VAT) content, improved insulin responsiveness and glucose tolerance, reduced steatosis, and reversed oxidant stress and the NRF2, GPX1, and GCLC expression. Furthermore, MASLD-related dysregulation of genes involved in lipid metabolism was restored, including vLDL transport (MTTP, APOB, and RASAL2), β-oxidation (PPAR-α, ACOX1, and FOXO1), lipogenesis (ACC1 and SREBP 1C), and fatty acid transport (PSD3 and CD36). In accordance, genes of key signaling pathways were also restored, including mTOR, TSC1, and TSC2, along with fibrosis and inflammation TGF-β, Fas, NF-κB, and IL-6. In VAT of MASLD animals, crown-like structures and adiposity density were diminished by CDP treatment, with increased expression of genes associated with beige-like adipose tissue remodeling, including PGC-1α, UCP1, NRF1, ATP6v1, CEBP-α, COX4i1, PPARγ, and CS. Consistently, the UCP1 and PGC-1α protein expression was increased in the VAT of MASLD animals treated with CDPs. Conclusions: The anti-MASLD effects of CDPs were associated with reversal of key pathogenic markers in the liver and VAT, suggesting remodeling of white adipose tissue (WAT) toward a beige-like adipose tissue phenotype. The findings suggest that CDPs may modulate adipose tissue structure and adipogenesis, underscoring their therapeutic relevance for MASLD. Full article

Objectives: To evaluate the impact of contrast phase, age, and sex on CT-derived body composition metrics—specifically attenuation and volume of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), liver, and skeletal muscle. The potential of the proportion of muscle voxels below 0 Hounsfield units (HU) as a surrogate for fatty infiltration was also explored. Materials and Methods: A retrospective analysis of 866 multiphasic abdominal CT scans (non-enhanced [NE], arterial [ART], portal venous [PV]) from 2012 to 2022 was performed. Segmentation of SAT, VAT, liver, and skeletal muscle was conducted using the AI-based TotalSegmentator. Wilcoxon signed-rank tests and Bland–Altman analysis (mean bias and 95% limits of agreement) were applied to assess contrast-related effects; Spearman’s correlation coefficient was used to assess demographic associations. Results: Significant variation in attenuation and volume of SAT, VAT, and muscle was observed across contrast phases (p < 0.001). SAT attenuation was higher in NE and PV than in ART, while VAT attenuation was highest in PV. SAT volume increased and VAT volume decreased in contrast-enhanced phases. Attenuation and volume showed strong inter-phase correlation (ρ > 0.9). VAT attenuation was significantly higher in females, whereas VAT volume was significantly greater in males. VAT volume negatively correlated with liver attenuation (ρ = −0.33). Muscle voxels <0 HU were significantly reduced in contrast-enhanced scans. Conclusions: Contrast phase, age, and sex significantly influence CT-based body composition parameters. These confounding factors should be considered when using quantitative imaging biomarkers in clinical and research settings. 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

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

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

Background: GDF15 (growth/differentiation factor-15) is part of the transforming growth factor-beta family and represents a cellular stress-induced gene. It might have a role in metaflammation and adipoflammation. We aimed to investigate the effects of Toll-like receptor (TLR) activation and hypoxia-related pathways together with metabolic factors on GDF15 regulation in adipocytes and adipose tissue (AT). Methods: GDF15 mRNA quantities in the human adipocyte cell line SGBS, in visceral (VAT) and subcutaneous adipose tissue (SAT) (resected from n = 96 obese and characterized patients), and in murine 3T3-L1 adipocytes were measured by real-time RT-PCR. GDF15 protein concentrations in cell supernatants and serum were quantified by ELISA. The following stimuli/pathways were investigated: insulin, glucose, TLR ligands (TLR2/6, TLR3, TLR4, TLR7, TLR9), bile acids, synthetic FXR/TGR5 activators, and HIF1α activators. Results: Basal GDF15 expression is low and only marginally induced in SGBS cells. In contrast, GDF15 is expressed in human SAT and VAT and correlates positively with the corresponding GDF15 protein concentration in peripheral blood serum of obese patients. Among metabolic factors, insulin and bile acids such as ursodeoxycholic acid upregulate GDF15 expression in 3T3-L1 adipocytes, the latter via FXR but not via TGR5. Among innate immune regulators, only TLR7 activation and hypoxic mediators upregulate whereas STAT3 signaling downregulates GDF15. Conclusion: GDF15 expression in human SAT and VAT is correlated to peripheral blood GDF15 concentrations and is regulated by metabolic and innate immune response pathways involved in AT inflammation and metaflammation. Full article

Visceral adipose tissue (VAT) is a metabolically active organ that undergoes structural and functional remodeling under obesogenic conditions. Early-life stress, such as maternal separation (MS), may modulate these processes, but its depot-specific effects remain poorly characterized. This study aimed to determine whether MS modulates VAT remodeling in response to post-weaning high-fat diet (HFD) exposure in male C57BL/6 mice. Animals underwent MS during the early postnatal period (PND2–16) or remained unmanipulated (UM), and were subsequently fed either a control diet (CD) or an HFD for 16 weeks (groups: UM-CD, UM-HFD, MS-CD, MS-HFD). Visceral adipose tissue was collected and analyzed at PND133. Perigonadal (PGAT), retroperitoneal (RPAT), and mesenteric (MSAT) visceral adipose tissue deposits were analyzed by histology, Picrosirius Red staining, and immunohistochemistry for leptin and UCP-1; apoptosis was assessed by TUNEL assay. HFD induced adipocyte hypertrophy and early inflammatory changes, while MS predominantly affected stromal organization. Collagen remodeling was depot-specific: PGAT showed an adaptive pattern, RPAT exhibited a significant MS×HFD interaction, and MSAT was primarily affected by MS regardless of diet. Leptin immunoreactivity increased with HFD in UM animals but was attenuated in MS mice, particularly in MSAT. UCP-1 signal was low and heterogeneous, without clear morphological browning. Apoptosis increased in MSAT under MS-HFD conditions. These findings indicate that early-life stress programs depot-specific VAT remodeling, with MSAT emerging as particularly susceptible to obesogenic challenge. Full article

Importance: Lifestyle and supportive care interventions may improve treatment tolerance, long-term health behaviors, and survivorship outcomes among breast cancer patients receiving radiotherapy. Few randomized trials have integrated nutrition, exercise, stress management, and psychosocial counseling concurrently with radiotherapy and extended across survivorship. Objective: To evaluate the effects of a comprehensive lifestyle intervention (CompLife) initiated during radiotherapy and maintained for 12 months on body composition, fitness, quality of life, symptoms, and nutrition. Design, Setting, and Participants: Randomized clinical trial at a single cancer center. Eligible women were aged ≥18 years with stage II/III breast cancer scheduled for radiotherapy, BMI ≥ 24.5, and ≥2 lifestyle risk factors. Participants were randomized to CompLife or standard of care (SOC). Assessments occurred at baseline, end of radiotherapy, and 3, 6, and 12 months. The primary outcome of recurrence is ongoing; this report examines prespecified secondary outcomes. Interventions: CompLife included 6 weeks of in-person counseling integrating nutrition, physical activity, mindfulness, stress management, and psychosocial support; twice-weekly exercise, diet, and mind–body sessions during radiotherapy; and telehealth counseling for 12 months. SOC participants received standard educational materials. Main Outcomes and Measures: Secondary outcomes included visceral adipose tissue (VAT), weight, waist circumference, fitness (VO₂ max, strength), SF-36 Physical and Mental Component Summary scores, MD Anderson Symptom Inventory scores, mindfulness (FFMQ), and dietary fiber intake. Results: Ninety-five women were randomized (CompLife, n = 50; SOC, n = 45). CompLife participants had lower VAT at 3 and 6 months (e.g., 3 months: 118 vs. 141 cm²; p = 0.044) and greater improvements in VO₂ max at 3 (23.4 vs. 18.8 mL/kg/min; p = 0.025) and 6 months. SF-36 Physical scores improved to within population norms for CompLife at all follow-ups but remained below norms in SOC. CompLife participants reported fewer symptoms at 12 months (MDASI: 1.3 vs. 2.5; p = 0.014). Fiber intake was consistently higher in CompLife participants (20.5 g vs. 14.0 g; p < 0.001). The results should be interpreted with caution due to the large number of comparisons among the secondary outcomes. Conclusions and Relevance: A multidisciplinary lifestyle intervention delivered during radiotherapy and extended across survivorship produced clinically meaningful improvements in body composition, fitness, diet, and patient-reported outcomes. The findings suggest potential value in integrating structured lifestyle and psychosocial counseling into oncology care and warrant confirmation in larger multicenter trials with mature recurrence endpoints. Full article

Background/Objectives: The benefits of vitamin K are well established in skeletal and cardiovascular health through activation of vitamin K-dependent proteins, including osteocalcin and matrix Gla protein. Emerging evidence also links vitamin K to pathways that influence body composition, including insulin sensitivity, adiponectin regulation, lipid oxidation, and inflammation. Vitamin K deficiency is linked to adverse health outcomes. We therefore evaluated whether menaquinone-7 (MK-7) supplementation alters body composition in adults with low vitamin K status. Methods: A total of 243 participants (166 women and 77 men) with low vitamin K status received 180 mcg of menaquinone-7 (MK-7), a form of Vitamin K, daily for one year. Changes in body mass index (BMI), body weight, fat mass, lean mass, and visceral adipose tissue (VAT) were assessed. Results: At baseline, higher dp-ucMGP, indicating lower vitamin K status, was positively associated with BMI (r = 0.223; p < 0.01), fat mass index (r = 0.200; p < 0.01), and VAT (r = 0.286; p < 0.001). After one year of supplementation, the total cohort showed a small but significant BMI reduction (−0.66%; p = 0.041). Responders (≥183 pmol/L dp-ucMGP drop) showed improvements in fat mass (−1.93%, p = 0.039), waist-to-hip ratio (−1.43%, p = 0.012), BMI (−1.37% ± 3.21, p = 0.004), and weight (−1.25%, p = 0.008), while non-responders exhibited an increase in VAT (+7.28%, p = 0.002). Women, especially premenopausal ones, experienced greater reductions in BMI, fat mass, and weight. dp-ucMGP levels significantly decreased in 90.9% of women (p < 0.001), whereas in men, although 77.8% showed a decrease, the change was not statistically significant. Among high responders (≥183 pmol/L dp-ucMGP reduction), both sexes demonstrated improvement, albeit significant body composition changes were seen only in women. Conclusions: Lower vitamin K status was associated with higher BMI, fat mass, and visceral adipose tissue. After one year of MK-7 supplementation, a modest reduction in BMI was observed, with more pronounced improvements in body composition among women. While these sex related differences may suggest that men require higher doses to achieve comparable responses, the current evidence remains preliminary. Further studies with larger cohorts are needed to clarify these findings. Full article

Background: In locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment. Pathologic complete response (pCR) is strongly associated with favorable long-term outcomes; however, reliable pre-treatment biomarkers for predicting treatment response remain limited. This study aimed to investigate the association between CT-derived adipose tissue parameters and pathologic response following neoadjuvant CCRT. Methods: A total of 61 patients with locally advanced rectal cancer who underwent neoadjuvant CCRT followed by surgery between 2020 and 2024 were retrospectively analyzed. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) parameters, including area, index, and mean attenuation (Hounsfield unit, HU), were measured at the L3 level on pre-treatment CT. Patients were classified into favorable (complete or near-complete response) and unfavorable response groups, as well as response and no-response groups. Statistical analyses included independent t-tests, chi-square tests, and receiver operating characteristic (ROC) curve analysis. Results: In the favorable versus unfavorable response analysis, higher body mass index (BMI), larger VAT area, higher VAT index (VATI), and lower mean VAT attenuation were significantly associated with favorable response (all p < 0.05), whereas SAT-related parameters were not. In the response versus no-response analysis, SAT area and SAT index (SATI), but not mean SAT attenuation and VAT-related parameters, were significantly associated with treatment response (all p < 0.05). BMI was significantly associated with pathologic response only in the favorable versus unfavorable response group analysis, whereas no significant association was observed in the response versus no-response group analysis. Conclusions: CT-derived adipose tissue parameters were differentially associated with pathologic response to neoadjuvant CCRT in locally advanced rectal cancer. VAT parameters, including both quantity and attenuation, were associated with favorable response, whereas SAT parameters were associated with overall treatment response, suggesting compartment-specific roles of adipose tissue in modulating treatment outcomes. While BMI demonstrated a significant association in one subgroup analysis, CT-based body composition analysis may provide more comprehensive and compartment-specific information beyond conventional anthropometric measures, and may serve as a potential imaging biomarker for predicting treatment response. Full article

Background/Objectives: Patients receiving maintenance hemodialysis (HD) commonly exhibit chronic low-grade inflammation, nutritional disturbances, altered body composition, and metabolic imbalance. Gut dysbiosis may contribute to these abnormalities through the gut–kidney axis; however, the relationship between the gut microbiota composition and host phenotype in HD patients remains incompletely characterized. This study aimed to characterize the gut microbiota composition in maintenance HD patients and assess its cross-sectional associations with demographic, inflammatory, nutritional, dialysis-related, and bioimpedance-derived body composition parameters. Methods: This single-center cross-sectional study included 96 patients with end-stage kidney disease undergoing maintenance HD. The primary objective was to characterize the gut microbiota composition in maintenance HD patients. Secondary objectives were to assess cross-sectional associations with demographic factors (sex, age) and bioimpedance-derived body composition (specifically VAT). Clinical and laboratory data, inflammatory markers, nutritional indicators, malnutrition–inflammation score (MIS), dialysis-related variables, and bioimpedance-derived body composition parameters were collected. Stool samples were analyzed using full-length 16S rRNA sequencing. The gut microbiota composition was assessed using taxonomic profiling, alpha-diversity and beta-diversity analyses, subgroup comparisons, and exploratory distance-based analyses. Associations were interpreted within a descriptive and hypothesis-generating framework. Results: The gut microbiota composition showed marked inter-individual heterogeneity at the genus level, with dominant taxa including Blautia, Faecalibacterium, Streptococcus, Gemmiger, Ruminococcus, Escherichia-Shigella, and Enterococcus. Chao1 richness was higher in men than in women. Shannon entropy and Chao1 richness were positively associated with age and visceral adipose tissue (VAT), while Faith’s phylogenetic diversity increased with age. In contrast, the Gini index was negatively associated with age and VAT, indicating a more even microbial community structure in older individuals and in those with higher visceral adiposity. Beta-diversity analyses suggested modest differences in microbial community structure according to sex and selected body composition-related categories, particularly in sex-stratified analyses. Exploratory distance-based analysis showed a modest association between overall microbiota dissimilarity and host phenotype dissimilarity, although this finding was limited by reduced sample overlap. Conclusions: The gut microbiota composition in maintenance HD patients was highly heterogeneous and showed cross-sectional associations, mainly with sex, age, visceral adiposity, and broader host phenotype. These findings suggest that microbiota variation in HD reflects multidimensional demographic, inflammatory, nutritional, metabolic, and body composition-related factors rather than a single clinical determinant. Larger longitudinal studies integrating standardized dietary, medication, metabolic, and clinical outcome data are needed to determine the prognostic relevance of these microbiota patterns. Full article

Background: Visceral adipose tissue (VAT) is a key determinant of cardiometabolic risk, yet its underlying molecular mechanisms remain incompletely characterized. Metabolomics offers an opportunity to identify circulating biomarkers that capture VAT-related biology beyond conventional clinical measures. Methods: We conducted a cross-sectional analysis of 2526 participants from the Qatar Biobank using untargeted serum metabolomics profiling. VAT was quantified using DXA-derived estimates and analyzed both as a continuous variable and by comparing individuals in the highest quartile to the remainder quartiles. Associations between metabolites and VAT were assessed using multivariate partial least squares discriminant analysis and adjusted linear regression models controlling for age, sex, and BMI, with Bonferroni correction for multiple testing. Results: Continuous VAT was associated with 106 metabolites, while the Q4 versus Q1–Q3 contrast identified 23 metabolites, with overlapping metabolites defining a robust core VAT signature. Higher VAT was characterized by coordinated elevation of branched-chain amino acids and their keto/hydroxy acid derivatives, glutamate, and central carbon intermediates, consistent with impaired mitochondrial oxidative decarboxylation. We further identified 4-hydroxyglutamate as a novel collagen-derived metabolite positively associated with VAT, suggesting a potential link between extracellular matrix remodeling and glutamate-centered metabolism. Additionally, greater VAT was associated with lower concentrations of glycine and glycine conjugates and reduced levels of unsaturated sphingomyelins and plasmalogens. Conclusions: These findings provide potential mechanistic insights into VAT-related metabolic dysfunction and identify candidate circulating biomarkers that may enable non-invasive assessment of visceral fat-associated cardiometabolic risk. Longitudinal and mechanistic studies are warranted to establish causality and clinical utility. Full article