RESUMEN
Adiposity contributes to multiple non-communicable diseases. To guide prevention of morbidity, this study aimed to quantify the relation between waist circumference (WC), body mass index (BMI), waist to height ratio (WtHR), abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) and the risk of a composite outcome including recurrent cardiovascular events, incident type 2 diabetes and incident cancer, as well as each individual disease and all-cause mortality. Data were used from the UCC-SMART cohort study from 6138 patients with cardiovascular disease. Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for adiposity measures, modelled as quartiles and per 1 SD increase, in relation to disease outcomes. All adiposity measures, except SAT, were related to higher risk of the composite outcome. WC and VAT showed the strongest relation (HR 1.62, 95% CI: 1.43, 1.83 and 1.62, 95% CI: 1.44, 1.83, respectively). Only WC and VAT were related to all-cause mortality (HRs 1.17, 95% CI: 1.01, 1.37 and 1.26, 95% CI: 1.08, 1.46, respectively). In patients with cardiovascular disease, WC and VAT are most strongly related to the risk of the composite outcome and to all-cause mortality. Monitoring adiposity with WC and VAT may help identify high-risk patients and could guide earlier interventions.
Asunto(s)
Adiposidad , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Neoplasias , Obesidad , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/etiología , Circunferencia de la Cintura , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Índice de Masa Corporal , Anciano , Factores de Riesgo , Modelos de Riesgos Proporcionales , Grasa Intraabdominal , Estudios de Cohortes , Adulto , Obesidad/complicacionesRESUMEN
OBJECTIVE: This cross-sectional study examined a Lifestyle Risk Factor Index (LSRI) in relation to adiposity measures including visceral adipose tissue (VAT) in the German National Cohort (NAKO). METHODS: Based on self-reports at baseline among 30,920 of > 205,000 NAKO eligible participants with magnetic resonance imaging (MRI) scans, one point each for not smoking, adhering to ≥ 3/7 diet recommendations, consuming ≤ 1 (women)/≤ 2 (men) alcoholic drinks/day, and ≥ 150 min/week physical activity was assigned. VAT volume, obtained from whole-body MRI at 3T, was analyzed by deep learning-based image segmentation. General linear models estimated adjusted geometric mean adiposity measures by LSRI and stratified analyses by sex and BMI. RESULTS: Of 18,508 participants aged 48.2 ± 12.2 years, the respective proportions for 0/1, 2, 3, and 4 LSRI points were 7%, 24%, 51%, and 18%. Participants with LSRI scores of 4 versus 0/1 had lower adjusted geometric mean volumes of VAT (2.3; 95% CI 2.2, 2.3 vs. 3.0; 95% CI 2.9, 3.1 L). These differences were slightly attenuated after adding BMI. This association was weaker for individuals with obesity than normal/overweight. CONCLUSION: A combination of lifestyle factors appears to be associated with lower VAT volume, but an elevated BMI may have a greater influence on VAT accumulation than lifestyle behaviors alone.
Asunto(s)
Grasa Intraabdominal , Estilo de Vida , Grasa Subcutánea , Humanos , Femenino , Masculino , Grasa Intraabdominal/diagnóstico por imagen , Persona de Mediana Edad , Grasa Subcutánea/diagnóstico por imagen , Alemania/epidemiología , Estudios Transversales , Imagen por Resonancia Magnética , Factores de Riesgo , Adulto , Índice de Masa Corporal , Adiposidad , Estudios de Cohortes , Ejercicio Físico , Obesidad/epidemiologíaRESUMEN
INTRODUCTION: Sarcopenia and adiposity at diagnosis are important prognostic factors in cancer. Ongoing changes in body composition during chemotherapy treatment may have additional prognostic relevance. This study aimed to investigate the association between body composition changes during neoadjuvant treatment and survival in patients with colorectal liver metastases. MATERIALS & METHODS: In this subgroup analysis of the newEPOC RCT (NCT00482222), pre- and post-treatment CT-scans of patients undergoing neoadjuvant chemotherapy for colorectal liver metastases were studied. The total cross-sectional area of skeletal muscle tissue (SM), Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT), Intra-Muscular Adipose Tissue (IMAT), and radiation attenuation for skeletal muscle (SM-RA) were determined. RESULTS: During neoadjuvant therapy, SM-index decreased from 50.6 ± 8.7 to 47.6 ± 8.6 cm2/m2, p < 0.001 for men and 40.5 ± 6.1 to 37.7 ± 5.9 cm2/m2, p = 0.002, for women. SM-RA decreased from 37.7 ± 7.8 to 36.0 ± 7.6 HU, p < 0.001 for men. VAT- and SAT-indices did not change significantly during treatment. Sarcopenia, SM-loss, SM-RA as baseline as well as change in SM-RA were not associated with overall survival, while intervention arm (HR1.96, 95 %CI1.21-3.19, p = 0.009), undergoing resection of the metastases (HR0.19, 95 %CI0.09-0.40, p < 0.001) and gaining >2 % VAT-index over 12 weeks (HR2.05, 95 %CI1.12-3.76, p = 0.025) were. CONCLUSIONS: The body composition features SM and SM-RA decreased during chemotherapy, but were not associated with survival. On the contrary, although VAT did not significantly change, the gain of VAT was an independent prognostic factor for survival. These results should be validated in independent cohorts but may indicate that in this selected patient group, adipose tissue might be a more important prognostic factor than sarcopenia.
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Neoplasias Colorrectales , Grasa Intraabdominal , Neoplasias Hepáticas , Músculo Esquelético , Sarcopenia , Humanos , Neoplasias Colorrectales/patología , Masculino , Femenino , Grasa Intraabdominal/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Persona de Mediana Edad , Sarcopenia/diagnóstico por imagen , Terapia Neoadyuvante , Anciano , Composición Corporal , Tomografía Computarizada por Rayos X , Tasa de Supervivencia , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Grasa Subcutánea/diagnóstico por imagenRESUMEN
This study evaluated the impact of maternal consumption of crude and refined Brazil nut oil on the physical, biochemical, and hepatic parameters of offspring in both male and female rats. Three maternal groups were formed: control (CG), crude oil (CO), and refined oil (RO), treated with 3,000 mg/kg of oil during gestation and lactation. The offspring were divided into male and female groups. Crude Brazil nut oil consumption resulted in increased body weight, total and mesenteric fat, as well as elevated coronary and cardiovascular risk indices. Conversely, the refined oil consumption reduced retroperitoneal fat and lowered the same risk indices. Both oils affected plasma triglycerides and cholesterol levels, with refined oil showing better results in lipid profiles, particularly by increasing HDL. The CO-F group exhibited higher blood glucose, while the RO-F group had lower glucose levels compared to CO-F. Changes in hepatic enzymes were observed, along with higher deposition of saturated fatty acids (SFA) and a reduction in mono and polyunsaturated fatty acids (MUFA and PUFA) in the liver of the offspring treated with crude oil. Lipid peroxidation was lower in the oil-treated groups compared to the control group. The effects were similar between male and female offspring. It was concluded that refined oil provided superior benefits compared to crude oil, improving biochemical parameters and hepatic health in the offspring.
Asunto(s)
Bertholletia , Suplementos Dietéticos , Lactancia , Hígado , Aceites de Plantas , Bertholletia/química , Aceites de Plantas/administración & dosificación , Aceites de Plantas/química , Aceites de Plantas/farmacología , Embarazo , Hígado/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Animales , Ratas , Masculino , Femenino , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Aumento de Peso , Triglicéridos/sangre , Colesterol/sangre , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/análisisRESUMEN
White matter hyperintensities or lesions (WMLs) increase the risk for cognitive impairment and dementia. Cardiometabolic factors (e.g., excess adiposity) and markers of systemic inflammation relate to greater WML volume, but few studies have examined whether specific compartments of adipose tissue (e.g., visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT)) relative to total body adiposity (TBA) differentially relate to WML volume or whether these patterns could be statistically mediated by inflammation. We examined associations between markers of low-grade systemic inflammation and compartments of adipose tissue relative to total body adiposity (rVAT or rASAT respectively), measured by dual-energy x-ray absorptiometry (DXA), and WML volume. We hypothesized that higher rVAT and not rASAT would be associated with greater WML volume, and that this association would be statistically mediated by concentrations of inflammatory cytokines. We used baseline data (n = 648) from the multisite study "Investigating Gains in Neurocognition in an Intervention Trial of Exercise" (IGNITE; mean age = 69.9 ± 3.8 years, 70.5 % females). IL-6, IL-1RA, and TNF-α were included as markers of systemic inflammation and age, sex, years of education, hypertension status, and study site were included as covariates. Our hypotheses were partially supported such that the relationship between rVAT and WMLs, as well as between rASAT and WMLs, were statistically mediated by IL-6 and TNF-α. These findings suggest that both higher rVAT and rASAT, are associated with higher WML burden through an elevated inflammatory state. These results set a testable mechanistic pathway for future longitudinal and intervention studies examining whether managing low-grade systemic inflammation and intentional weight loss would be beneficial for supporting brain health in older adults.
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Adiposidad , Inflamación , Sustancia Blanca , Humanos , Masculino , Femenino , Inflamación/metabolismo , Inflamación/patología , Anciano , Sustancia Blanca/patología , Sustancia Blanca/diagnóstico por imagen , Adiposidad/fisiología , Persona de Mediana Edad , Absorciometría de Fotón , Grasa Intraabdominal/metabolismo , Imagen por Resonancia Magnética , Interleucina-6/sangre , CitocinasRESUMEN
Obesity-induced inflammation in visceral adipose tissue (VAT) is a major driver of metabolic dysfunctions, contributing to severe health conditions such as insulin resistance, diabetes, and fatty liver disease. Current anti-inflammatory therapies lack specificity, often leading to systemic immune suppression. To address this challenge, this study develops a nanosilicon-based hydrogen (H2)-generating nanostructure coated with a positively charged copolymer layer, specifically designed for targeted immunomodulation within VAT. Following intraperitoneal administration in high-fat diet-fed obese mice, the positively charged H2-generating nanostructure selectively accumulates in the expanded extracellular matrix of obese VAT through electrostatic attraction to its negatively charged components. Once accumulation, it reacts with body fluids to sustainably generates H2. This continuous H2 release reprograms the local immune microenvironment by balancing pro-inflammatory M1 and anti-inflammatory M2 adipose tissue macrophages, effectively mitigating VAT inflammation and restoring adipocyte function. In addition to its localized effects, this intervention improves systemic lipid and glucose metabolism, highlighting its potential to address obesity-associated metabolic dysfunctions. By targeting VAT inflammation with high specificity and minimal side effects, this H2-based nanotechnology offers a promising therapeutic strategy for obesity and its related metabolic disorders.
Asunto(s)
Hidrógeno , Inmunomodulación , Inflamación , Enfermedades Metabólicas , Nanoestructuras , Obesidad , Animales , Obesidad/complicaciones , Obesidad/inmunología , Obesidad/metabolismo , Inflamación/inmunología , Inflamación/etiología , Inflamación/tratamiento farmacológico , Ratones , Hidrógeno/química , Inmunomodulación/efectos de los fármacos , Ratones Endogámicos C57BL , Nanoestructuras/química , Dieta Alta en Grasa/efectos adversos , Masculino , Grasa Intraabdominal/inmunología , Grasa Intraabdominal/patología , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , AdipocitosRESUMEN
OBJECTIVE: Severe obesity poses a major public health concern due to its links with cardiometabolic complications and mortality. Visceral adipose tissue (VAT) plays a key role in these processes through distinct molecular features. This study aimed to characterize the VAT proteome of individuals with severe obesity and investigate its association with serum metabolic biomarkers. METHODS: A cross-sectional analysis was performed for 46 individuals with severe obesity undergoing metabolic bariatric surgery and 17 healthy controls undergoing elective abdominal surgery. VAT proteomes were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and serum metabolites were quantified using nuclear magnetic resonance-based metabolomics. RESULTS: LC-MS/MS identified 22 differentially expressed proteins (FDR < 0.05) in VAT with 12 downregulated and 10 upregulated in severe obesity. Downregulated proteins included mitochondrial enzymes involved in substrate metabolism and mitochondrial transmembrane transport. Circulating glucose, valine, and isoleucine correlated negatively with VAT mitochondrial transmembrane and electron transport proteins. Upregulated proteins were associated with inflammation, immune activation, oxidative stress, cytoskeletal remodeling, and protein turnover. CONCLUSIONS: These findings demonstrate significant molecular alterations in the VAT proteome associated with severe obesity, providing insights into the underlying mechanisms of metabolic disease. The differentially expressed proteins may serve as biomarkers or therapeutic targets for obesity-related complications. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00793143 and NCT01373892.
Asunto(s)
Inflamación , Grasa Intraabdominal , Obesidad Mórbida , Proteoma , Humanos , Grasa Intraabdominal/metabolismo , Masculino , Femenino , Proteoma/metabolismo , Estudios Transversales , Persona de Mediana Edad , Adulto , Obesidad Mórbida/metabolismo , Obesidad Mórbida/cirugía , Biomarcadores/sangre , Biomarcadores/metabolismo , Inflamación/metabolismo , Espectrometría de Masas en Tándem , Estudios de Casos y Controles , Cirugía Bariátrica , Cromatografía LiquidaRESUMEN
Abnormalities in triacylglycerol metabolism can lead to excessive visceral fat accumulation. Though diacylglycerol (DAG) administration could reduce serum total triacylglycerol (TG), its impact on visceral fat deposition and potential mechanisms remains unclear. This trial aimed to evaluate the impact of substituting regular rapeseed cooking oil (TAG) with DAG oil on primary outcomes such as anthropometric measurements and lipid profiles, as well as secondary outcomes including visceral fat and serum lipidomics in Chinese adults with overweight/obesity or central obesity. Ninety-five participants (BMI: 25.93 ± 2.92 kg m-2) were assigned to the DAG or TAG group through random allocation. Over 8 weeks, participants were provided similar diets cooked with DAG or TAG oil, respectively. By week 8, the serum TG (P = 0.026) and small dense low-density lipoprotein cholesterol (sdLDL-C) (P = 0.024) levels in the DAG group were significantly lower than those in the TAG group. The change in sdLDL-C was notably greater in the DAG group than in the TAG group (-0.10 ± 0.12 vs. -0.03 ± 0.16), and a significant decrease in the levels of waist circumference, hip circumference, total cholesterol, and sdLDL-C was only observed in the DAG group compared with the baseline (all P < 0.05). Imaging analyses revealed that attenuation of hepatic steatosis was observed in the DAG group compared with the TAG group (P = 0.035), and a decrease in visceral fat area was found only in the DAG group compared with the baseline (P < 0.001). Lipidomic profiling demonstrated DAG induced enrichment of serum triacylglycerol and phosphatidylethanolamine species containing mono/polyunsaturated fatty acids, which were associated with the enhanced adipocyte lipolysis and thermogenesis. These findings suggested that DAG-mediated lipid remodeling might be related to preventing lipid metabolic disorders through visceral fat regulation.
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Diglicéridos , Metabolismo de los Lípidos , Obesidad Abdominal , Obesidad , Sobrepeso , Humanos , Masculino , Diglicéridos/administración & dosificación , Diglicéridos/metabolismo , Femenino , Adulto , Método Doble Ciego , Persona de Mediana Edad , Sobrepeso/metabolismo , Sobrepeso/dietoterapia , Obesidad Abdominal/metabolismo , Obesidad Abdominal/dietoterapia , Obesidad Abdominal/tratamiento farmacológico , Triglicéridos/sangre , Metabolismo de los Lípidos/efectos de los fármacos , China , Obesidad/metabolismo , Grasa Intraabdominal/metabolismo , Lipidómica , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Methotrexate (MTX) is essential for treating lymphoblastic leukemia, but high doses (5 g/m2 corporal surface) can cause significant gastrointestinal, renal, hepatic, and hematological toxicity. Body composition, particularly high body fat mass, can function as a third space and may increase toxicity by prolonging the drug's circulation time. AIM: To analyze the associations between body composition (body fat mass, visceral fat area, and skeletal muscle mass) and the incidence of MTX toxicity in patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. MATERIALS AND METHODS: A cohort of patients aged 6-18 years diagnosed with ALL and lymphoblastic lymphoma who received high-dose MTX without prior toxicity was included. Patients with preexisting renal failure or liver failure before MTX administration were excluded. Body composition was assessed using a multifrequency bioimpedance device. RESULTS: Regarding MTX toxicity, 30.2% of events occurred early, and this figure increased to 58.7% for late toxicity. Patients with a visceral fat area (VFA) ≥47 cm2 had a significantly higher risk of late toxicity (RR 2.8 (1.3-5.5), p = 0.01), as did those with high body fat mass (RR 2.0 (1.1-3.4), p = 0.01). For severe late toxicity, a VFA ≥47 cm2 was strongly correlated (RR 5.6 (1.3-22.6), p = 0.003), and high body fat mass remained a significant risk factor (RR 2.3 (1.03-5.5), p = 0.03). No significant associations were found with low phase angle, low skeletal muscle index, or overweight body mass index. CONCLUSION: A VFA ≥ 47 cm2 and a high percentage of body fat mass were associated with an increased risk of late MTX toxicity and severe late toxicity.
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Tejido Adiposo , Antimetabolitos Antineoplásicos , Grasa Intraabdominal , Metotrexato , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metotrexato/efectos adversos , Niño , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Masculino , Adolescente , Femenino , Grasa Intraabdominal/patología , Grasa Intraabdominal/efectos de los fármacos , Factores de Riesgo , Antimetabolitos Antineoplásicos/efectos adversos , Composición Corporal , Pronóstico , Tejido Adiposo/patología , Estudios de SeguimientoRESUMEN
BACKGROUND: Sarcopenia and altered body composition have been associated with poor outcomes in cancer patients. We investigated whether skeletal muscle index (SMI), visceral fat area (VFA), and subcutaneous fat area (SFA) measured on CT scans predict survival in non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitor therapy. METHODS: This retrospective pilot study analyzed 46 NSCLC patients who had CT scans within 60 days of initiating checkpoint inhibitor therapy (93.5% pembrolizumab, 6.5% nivolumab) at a single tertiary care center. Body composition metrics were measured at the L3 vertebral level using TeraRecon software by a trained reader. Sarcopenia was defined using validated cutoffs (males < 45.4 cm2/m2, females < 34.4 cm2/m2). Cox proportional hazards models evaluated associations between body composition and survival, with analyses stratified by sex. RESULTS: The cohort included 25 males (54.3%) and 21 females (45.7%), with median time from CT scan to checkpoint inhibitor initiation of 14 days (IQR: -47 to 18). One-year survival was 72.0% for males and 59.3% for females; two-year survival was 33.7% and 27.3%, respectively. Those who met the clinical criteria for sarcopenia did not statistically differ in survival compared to those who did not meet the clinical cut off (HR 1.21 (95% CI 0.63, 2.43). This finding remained consistent when males and females were examined separately and when the model was adjusted for timing to checkpoint inhibitor. CONCLUSION: In this small pilot study, pre-treatment body composition metrics did not significantly predict survival in NSCLC patients receiving checkpoint inhibitors. However, the study was likely underpowered with wide confidence intervals, limiting definitive conclusions. These findings provide a methodological framework for larger multicenter studies to validate the prognostic utility of CT-derived body composition in this population.
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Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Sarcopenia , Humanos , Femenino , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Estudios Retrospectivos , Grasa Subcutánea/diagnóstico por imagen , Anciano , Proyectos Piloto , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Tomografía Computarizada por Rayos X , Grasa Intraabdominal/diagnóstico por imagen , Composición Corporal , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Músculo Esquelético/diagnóstico por imagenRESUMEN
Background/Aims: The aim of this study is to investigate whether the creeping fat (CF) finding evaluated by computed tomography (CT) can be used as a noninvasive marker to predict disease prognosis. Materials and Methods: The study comprised 128 Crohn's patients, aged 18-70, who had CT scanning for a variety of reasons. Patients were retrospectively analyzed in 3 groups (31 patients with operation due to stenosis, 39 patients with unoperated stenosis, and 44 patients without stenosis). The CF Index BSACR (bowel surface area coverage ratio), CF density, and visceral-subcutaneous fat ratio (VSFR) findings were evaluated by CT compared between the groups. Results: The median VSFR was higher in the stenosed group compared to the non-stenosed group (0.7 vs 0.4; P = .003). The CF index BSACR was 37.5% (27.1% vs 18.2%; P = .001), and the rate of those with a CF index BSACR above 37.5% was higher in those with stenosis compared to those without. The odds of stenosis were 17.07 times (odds ratio [OR] = 17.07; P = .007) higher in those with a CF index BSACR of 37.5% and 184.57 times (OR = 184.57; P = .001) higher in those with a CF index BSACR of 50% or more compared to those with no involvement or a CF index BSACR of 25% or less. Conclusion: The CF index correlated with stricturing disease and may be a noninvasive radiologic marker that predicts disease prognosis.
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Enfermedad de Crohn , Obstrucción Intestinal , Grasa Intraabdominal , Tomografía Computarizada por Rayos X , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Enfermedad de Crohn/complicaciones , Masculino , Femenino , Adulto , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/etiología , Grasa Intraabdominal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Obstrucción Intestinal/diagnóstico por imagen , Valor Predictivo de las PruebasRESUMEN
Obesity is correlated with the development of multiple cancer types, and obese patients with pancreatic ductal adenocarcinoma (PDAC) show dismal prognosis and resistance to immune checkpoint blockade (ICB) therapy. The molecular mechanism is largely unknown. Here, we show that obese visceral adipose tissues (VATs) can communicate with distant PDAC by delivering extracellular vesicles (EVs) carrying signal molecules. We reveal that PDAC cells can take VAT-EVs into their lysosomes, where EV-delivered cathepsin A (Ctsa) stabilizes the ribonuclease Rnaset2b to produce free pseudouridine. Pseudouridine activates mast cells via increasing reactive oxygen species (ROSs) and decreasing H3K27me3 modification at the gene promoter. Activated mast cells inhibit CD8+ T cell activity, forming an immunosuppressive tumor microenvironment that enhances cancer progression. Animal experiments indicate that Ctsa knockdown effectively enhances ICB efficacy on PDAC. Our study uncovers a VAT-EV CTSA-pseudouridine-mast cell axis connecting obesity and cancer, which holds promise for developing new therapeutic strategies for obesity-related cancers.
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Carcinoma Ductal Pancreático , Resistencia a Antineoplásicos , Vesículas Extracelulares , Inhibidores de Puntos de Control Inmunológico , Grasa Intraabdominal , Obesidad , Neoplasias Pancreáticas , Vesículas Extracelulares/metabolismo , Humanos , Animales , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/patología , Ratones , Grasa Intraabdominal/metabolismo , Grasa Intraabdominal/patología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Microambiente Tumoral , Línea Celular Tumoral , Ratones Endogámicos C57BL , Mastocitos/metabolismo , MasculinoRESUMEN
BACKGROUND/OBJECTIVES: Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, has been linked to poor oncological outcomes. This study aimed to assess the relationship between sarcopenia-defined through combined radiological and biochemical assessments-and survival outcomes in patients with rectal cancer. METHODS: Sarcopenia was evaluated using radiological measurements of skeletal muscle mass, visceral and subcutaneous fat tissue volumes, and biochemical parameters including albumin, protein, and Fib-4 index levels. RESULTS: Deceased patients were older than survivors (mean 70 vs. 63years). Elevated Fib-4 scores (3.0-4.9) were mainly observed in non-operated patients with poor tumor regression. Post-treatment albumin levels were significantly higher in patients with complete response (42.0±3.5mg/dL) than in those with regression score-3 (37.3±8.7mg/dL) and non-operated patients (34.9±8.3mg/dL; p < 0.001). Pre-treatment skeletal muscle mass, subcutaneous fat, and visceral fat volumes were greater in survivors (22.3±7.0cm3 vs 19.2±7.0cm3, 27.7±20.3cm3 vs 18.7±14.0cm3 and 49.7±37.8cm3 vs 29.9±20.5cm3 respectively) than in deceased patients (p < 0.05). Larger tissue volumes-muscle≥16.95cm3, visceral fat≥39.35cm3, and subcutaneous fat≥17.65 cm3 were associated with longer overall survival. In univariate analysis, older age, low albumin, high Fib-4 index, and reduced tissue volumes predicted poorer survival, while multivariate analysis identified low post-treatment albumin as the only independent prognostic factor (HR 0.28, 95% CI:0.12-0.65, p = 0.003). CONCLUSIONS: Sarcopenia is associated with decreased overall survival in rectal cancer. In patients receiving neoadjuvant therapy, lower volumes of muscle mass, subcutaneous fat, and visceral fat, together with lower albumin and protein levels and higher Fib-4 scores, may serve as predictive markers of sarcopenia.
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Neoplasias del Recto , Sarcopenia , Humanos , Sarcopenia/mortalidad , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiología , Neoplasias del Recto/mortalidad , Neoplasias del Recto/complicaciones , Neoplasias del Recto/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Pronóstico , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/patología , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/patología , Albúmina Sérica , Anciano de 80 o más AñosRESUMEN
This study explores the role of human visceral white adipocytes (hv-WAD) in latent tuberculosis infection (LTBI). While granulomas and macrophages are traditionally viewed as central to TB latency, emerging evidence highlights adipocytes as significant non-canonical host cells that may facilitate bacterial persistence by providing a protective niche. Unlike the immune-driven environment within granulomas, adipocytes can shield Mycobacterium tuberculosis (Mtb) from immune surveillance, promoting survival. In vitro experiments showed that Mtb invades approximately 39% of hv-WAD within 48-72 h post-infection (hpi). Both avirulent H37Ra and virulent H37Rv Mtb strains, when infecting adipocytes, expressed RNA for key virulence factors (19 kDa, 30 kDa, Ag85b, 5KST, CFP10, and ESAT6) and dormancy-associated genes (Icl1, LipY, WhiB3, SodA, and Tgs1) at 72 hpi. Infection stimulated the production of inflammatory cytokines, notably leading to a fivefold increase in TNF-α with H37Rv (p < 0.01). Additionally, we detected Mtb RNA transcripts (IS6110, 5KST, 30 kDa, CFP10, Ag85) in 68% of biopsies from TB asymptomatic patients. The transcripts suggest a metabolically heterogeneous state of mycobacteria. These findings position visceral fat as a potential reservoir for Mtb in latent TB infection and underscore the development of novel diagnostic strategies targeting adipose tissue.
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Adipocitos Blancos , Citocinas , Infección por M. tuberculosis , Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Infección por M. tuberculosis/microbiología , Infección por M. tuberculosis/metabolismo , Infección por M. tuberculosis/genética , Infección por M. tuberculosis/inmunología , Citocinas/metabolismo , Citocinas/genética , Adipocitos Blancos/microbiología , Adipocitos Blancos/metabolismo , Adipocitos Blancos/inmunología , Femenino , Masculino , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Adulto , Grasa Intraabdominal/microbiología , Persona de Mediana Edad , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
Background/Objectives: Increased fat intake and high content of saturated fatty acids in the diet are associated with higher body weight and an increased risk of obesity. This study aimed to determine the impact of a high-fat diet (HFD) on white adipose tissue (WAT) metabolism and to verify whether this effect depends on the sources of lipids in HFD. Methods: Male C57BL/6J mice, 7 weeks old, received a control (Ctrl.) or high-fat diet (HFD) with 10% and 45% energy from fat, respectively, for 15 weeks. Lard was used as the main dietary fat in the HFD group. Next, the HFD group was subdivided into HFD-L, HFD-CO, HFD-OO and HFD-FO groups differing in the lipid sources (lard, coconut oil, olive oil, fish oil, respectively). The experiment was continued for 12 consecutive weeks. The study analyzed the concentration of different fatty acids in visceral (VAT) and subcutaneous (ScAT) adipose tissue; the levels of autophagy markers: beclin1, Atg5, LC3, p62, AMPK; ER stress markers: phos-PERK, CHOP, XBP-1 and oxidative stress parameters: TAS and TBARS in VAT and ScAT. Results: Mice in all HFD groups showed increased body mass and adipose tissue hypertrophy. Blood glucose concentration remained elevated in the HFD-L group but normalized in other HFD groups by the end of the dietary intervention. Fatty acid content in VAT and ScAT reflected the dietary sources in HFD. The HFD-L, HFD-CO, HFD-OO groups showed increased beclin1, ATG5, and p62 levels in VAT but the LC3-II/LC3-I ratio was similar to the control, suggesting impaired autophagic flux. In the HFD-FO group, the LC-II/LC-I ratio was elevated, along with decreased p62 levels, indicating active autophagic degradation. Changes in autophagy activity were insignificant in ScAT. ER stress markers were also mostly unaffected by HFD in both adipose tissue depots. TAS and TBARS values in VAT and ScAT were similar in the HFD-L and HFD-CO groups, and the HFD-OO group showed increased TAS and decreased TBARS, while the HFD-FO reduced TBARS. Conclusions: Antioxidant capacity and autophagy activity in WAT depended on fat content and lipid source, especially in the visceral depot. Fish oil induced changes in cellular metabolism, especially in VAT, diminishing the detrimental effects of HFD.
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Tejido Adiposo Blanco , Tejido Adiposo , Autofagia , Dieta Alta en Grasa , Grasas de la Dieta , Aceites de Pescado , Estrés Oxidativo , Animales , Autofagia/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Aceites de Pescado/farmacología , Aceites de Pescado/administración & dosificación , Ratones , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/metabolismo , Grasa Intraabdominal/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Obesidad/etiología , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de los fármacosRESUMEN
Introduction: Psoriasis patients are frequently exposed to residual inflammation and visceral obesity, two factors that synergistically increase cardiometabolic risk. Methods: We evaluated IL-6 as a potential integrative biomarker linking these pathways in a cross-sectional study including 80 patients with well-controlled skin disease and 20 matched healthy controls. Serum IL-6 was measured by ELISA, and visceral adiposity estimated using the Visceral Adiposity Index (VAI). Results: Psoriasis patients displayed significantly higher IL-6 than controls (38.1 pg/mL [35.5-41.3] vs. 21.4 pg/mL [19.5-33.4]; p<0.001). A distinct VAI threshold of 1.3 was identified, above which IL-6 levels rose steeply until VAI 2.2 and then plateaued. Patients with VAI ≥1.3 had markedly higher IL-6 and pro-inflammatory cytokines than those below this cutoff. Random forest regression confirmed IFN-γ, IL-1ß, IL-12p70, and IL-17 as dominant predictors of IL-6, while HbA1c, FIB-4, and treatment contributed minimally. Discussion: These findings suggest that IL-6 elevation in psoriasis primarily reflects cytokine-driven residual inflammation, with non-linear amplification once visceral adiposity exceeds a critical threshold. The threshold-dependent IL-6 dynamic highlights a clinically meaningful inflection point, integrating residual inflammation and visceral fat dysfunction, and may guide early cardiometabolic risk stratification and intervention. Prospective validation is warranted.
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Inflamación , Interleucina-6 , Grasa Intraabdominal , Obesidad Abdominal , Psoriasis , Humanos , Psoriasis/sangre , Psoriasis/inmunología , Psoriasis/diagnóstico , Masculino , Biomarcadores/sangre , Femenino , Interleucina-6/sangre , Persona de Mediana Edad , Adulto , Estudios Transversales , Inflamación/sangre , Obesidad Abdominal/sangre , Obesidad Abdominal/diagnóstico , Adiposidad , Citocinas/sangreRESUMEN
Background: Increasing studies have suggested that bone closely interacts with bone marrow adipose tissue (BMAT) and abdominal adipose tissue. However, this relationship remains debated. This study aimed to explore the association among BMAT, abdominal adipose tissue, and lumbar volumetric bone mineral density (vBMD). Methods: A total of 306 Chinese adult living liver transplant donors were enrolled in this cross-sectional study. vBMD and abdominal adipose tissue in terms of total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), were derived using quantitative computed tomography (QCT). Chemical shift encoded magnetic resonance imaging (MRI) of the lumbar spine was performed, and proton density fat fraction (PDFF) maps were calculated. Correlation analysis and multiple linear regression were used to assess the associations among BMAT, abdominal adipose tissue distribution, and vBMD. Results: The mean age of the participants was 38.1 ± 9.5 years (range: 19-66 years). The vBMD was significantly negatively associated with age (r = -0.508, p < 0.001), VAT (r = -0.235, p < 0.001), TAT (r = -0.127, p = 0.03), and BMAT measured by PDFF (r = -0.642, p < 0.001). After adjusting for age, gender, and BMI, multiple linear regression analysis showed BMAT (ß = -0.523, p < 0.001), SAT (ß = 0.116, p = 0.045) and VAT (ß = -0.108, p = 0.037) to be independent factors influencing vBMD. Conclusion: Our results indicated a negative association between BMAT and BMD. The association between abdominal adipose tissue distribution and BMD was dual; there was a positive association between SAT and BMD and a negative association between VAT and BMD. These findings suggest that the distribution of abdominal adipose tissue, particularly visceral adipose tissue accumulation, should be prioritized over total body weight in considerations of bone health.
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Grasa Abdominal , Tejido Adiposo , Densidad Ósea , Médula Ósea , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Grasa Abdominal/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Densidad Ósea/fisiología , Médula Ósea/diagnóstico por imagen , China , Estudios Transversales , Grasa Intraabdominal/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Imagen por Resonancia Magnética , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Postoperative inflammatory ileus (PII) is characterised by long-term re-obstruction, following temporary defecation. An intestinal fistula excision (IFE) with severe abdominal adhesions could increase the risk of PII in patients with sarcopenia. On the other hand, the postoperative outcomes are negatively impacted owing to chronic preoperative inflammation, as measured by the visceral fat area (VFA) and the total abdominal muscle area index (TAMAI) ratio. This study aims to evaluate the predictability of VFA/TAMAI for postoperative PII after IFE. METHODS: Four tertiary centres participated in this retrospective cohort study. Patients with sarcopenia who underwent IFE between January 2018 and October 2022 were enrolled. VFA/TAMAI was evaluated as a risk factor for PII. RESULTS: We included 177 eligible patients (102 [57.6%] males) with a median age of 51 years (interquartile range [IQR]: 38-61 years) in this study. PII occurred in 16.9% of patients (n = 30), with an interval of four days (IQR: 3-5 days) between IFE and temporary defecation. The duration of the re-obstruction after temporary defecation was 23 days (IQR: 21-30 days), following temporary defecation that lasted for one days (IQR: 1-2 days). The adjusted logistic regression revealed that VFA/TAMAI was associated with PII (odds ratio = 1.51, 95% confidence interval: 1.02-2.19; p = 0.03). CONCLUSION: VFA/TAMAI was associated with inflammatory ileus after IFE with severe abdominal adhesions in patients with sarcopenia.
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Músculos Abdominales , Ileus , Fístula Intestinal , Grasa Intraabdominal , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adherencias Tisulares/complicaciones , Complicaciones Posoperatorias/etiología , Ileus/etiología , Adulto , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/patología , Fístula Intestinal/cirugía , Fístula Intestinal/complicaciones , Músculos Abdominales/patología , Músculos Abdominales/diagnóstico por imagen , Sarcopenia/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: To evaluate the impact of different abdominal adipose tissue segmentation strategies on radiomics-based models for predicting 3-year disease progression in patients with Crohn's disease (CD). METHODS: In this retrospective dual-center study, patients with CD who underwent baseline CT enterography (CTE) were included. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were segmented using three approaches: (1) whole-abdomen segmentation (T-VAT/SAT); (2) single-slice segmentation of adipose tissue surrounding the most severely affected bowel segment (LL-VAT/SAT); and (3) single-slice segmentation at individual vertebral levels from L3 to S2 (V-VAT/SAT). Radiomic features were extracted after preprocessing, and redundant features were removed. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO), followed by construction of logistic regression models. A combined model incorporating radiomics and clinical features was also constructed. Model performance was evaluated using receiver operating characteristic (ROC), area under the precision-recall curve (AUPRC), and decision curve analysis (DCA). RESULTS: In the external test set, the T-VAT model achieved an AUC of 0.877 (95% CI: 0.718-0.937) and an AUPRC of 0.657 (95% CI: 0.368-1.000), performing better than other VAT- and SAT-based models. The combined model, which incorporated clinical features with the T-VAT model, showed an AUC of 0.873 (95% CI: 0.711-1.000) and the highest AUPRC of 0.666 (95% CI: 0.376-1.000). DCA further demonstrated that the combined model provided greater net clinical benefit compared with both the T-VAT and clinical models. CONCLUSIONS: Radiomics based on whole-abdominal VAT segmentation achieved the best prognostic performance for predicting disease progression in CD. Appropriate selection of adipose tissue segmentation strategy is critical for developing robust radiomics models for outcome prediction. CLINICAL TRIAL NUMBER: Not applicable.
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Grasa Abdominal , Enfermedad de Crohn , Grasa Intraabdominal , Tomografía Computarizada por Rayos X , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Femenino , Masculino , Estudios Retrospectivos , Adulto , Tomografía Computarizada por Rayos X/métodos , Pronóstico , Persona de Mediana Edad , Grasa Abdominal/diagnóstico por imagen , Progresión de la Enfermedad , Grasa Intraabdominal/diagnóstico por imagen , Adulto Joven , RadiómicaRESUMEN
INTRODUCTION: Postoperative incisional hernia impairs patients' quality of life and may require surgical intervention. This study investigated the risk of incisional hernia following laparoscopic colorectal cancer surgery. METHODS: In total, 199 patients who underwent laparoscopic colorectal cancer surgery were enrolled in this retrospective single-center study. The patients were divided into the no incisional hernia group (n = 185) and the incisional hernia group (n = 9). Subcutaneous fat area (SFA) and visceral fat area (VFA) at the level of the umbilicus were measured using specialized computed tomography imaging software. Data from an additional 78 patients who underwent laparoscopic colorectal cancer surgery in another hospital were used as a validation cohort. RESULTS: Nine patients (4.6%) were diagnosed with incisional hernia. Body mass index, SFA, and VFA were significantly higher in the hernia group than in the non-hernia group (p = 0.04, 0.004, and 0.03, respectively). In the multivariate analysis, only SFA of ≥ 167.8 cm2 remained an independent risk factor (odds ratio: 7.73, 95% confidence interval: 1.31-45.8, p = 0.02). Subcutaneous fat thickness (SFT), which can be easily measured on routine computed tomography scans, showed a strong correlation with SFA (coefficient = 0.779, p < 0.001) and was also significantly associated with incisional hernia. This association was validated in an independent cohort. CONCLUSION: High SFA was an independent risk factor for incisional hernia following laparoscopic colorectal cancer surgery. SFT may serve as a practical surrogate for SFA.