RESUMEN
The 'apple-shaped' anatomical pattern that accompanies visceral adiposity increases risk for multiple chronic diseases, including conditions that impact the brain, such as diabetes and hypertension. However, distinguishing between the consequences of visceral obesity, as opposed to visceral adiposity-associated metabolic and cardiovascular pathologies, presents certain challenges. This review summarizes current literature on relationships between adipose tissue distribution and cognition in preclinical models and highlights unanswered questions surrounding the potential role of tissue- and cell type-specific insulin resistance in these effects. While gaps in knowledge persist related to insulin insensitivity and cognitive impairment in obesity, several recent studies suggest that cells of the neurovascular unit contribute to hippocampal synaptic dysfunction, and this review interprets those findings in the context of progressive metabolic dysfunction in the CNS. Signalling between cerebrovascular endothelial cells, astrocytes, microglia, and neurons has been linked with memory deficits in visceral obesity, and this article describes the cellular changes in each of these populations with respect to their role in amplification or diminution of peripheral signals. The picture emerging from these studies, while incomplete, implicates pro-inflammatory cytokines, insulin resistance, and hyperglycemia in various stages of obesity-induced hippocampal dysfunction. As in the parable of the five blind wanderers holding different parts of an elephant, considerable work remains in order to assemble a model for the underlying mechanisms linking visceral adiposity with age-related cognitive decline.
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Disfunción Cognitiva , Hipocampo , Hiperglucemia , Hiperinsulinismo , Inflamación , Obesidad Abdominal , Animales , Disfunción Cognitiva/etiología , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/metabolismo , Hipocampo/inmunología , Hipocampo/metabolismo , Hipocampo/fisiopatología , Humanos , Hiperglucemia/etiología , Hiperglucemia/inmunología , Hiperglucemia/metabolismo , Hiperinsulinismo/etiología , Hiperinsulinismo/inmunología , Hiperinsulinismo/metabolismo , Inflamación/etiología , Inflamación/inmunología , Inflamación/metabolismo , Obesidad Abdominal/complicaciones , Obesidad Abdominal/inmunología , Obesidad Abdominal/metabolismoRESUMEN
AIMS: To explore variables associated with the serological response following COVID-19 mRNA vaccine. METHODS: Eighty-six healthcare workers adhering to the vaccination campaign against COVID-19 were enrolled in January-February 2021. All subjects underwent two COVID-19 mRNA vaccine inoculations (Pfizer/BioNTech) separated by 3 weeks. Blood samples were collected before the 1st and 1-4 weeks after the second inoculation. Clinical history, demographics, and vaccine side effects were recorded. Baseline anthropometric parameters were measured, and body composition was performed through dual-energy-X-ray absorptiometry. RESULTS: Higher waist circumference was associated with lower antibody (Ab) titres (R = -0.324, p = 0.004); smokers had lower levels compared to non-smokers [1099 (1350) vs. 1921 (1375), p = 0.007], as well as hypertensive versus normotensive [650 ± 1192 vs. 1911 (1364), p = 0.001] and dyslipideamic compared to those with normal serum lipids [534 (972) vs 1872 (1406), p = 0.005]. Multivariate analysis showed that higher waist circumference, smoking, hypertension, and longer time elapsed since second vaccine inoculation were associated with lower Ab titres, independent of BMI, age. and gender. CONCLUSIONS: Central obesity, hypertension, and smoking are associated with lower Ab titres following COVID-19 vaccination. Although it is currently impossible to determine whether lower SARS-CoV-2 Abs lead to higher likelihood of developing COVID-19, it is well-established that neutralizing antibodies correlate with protection against several viruses including SARS-CoV-2. Our findings, therefore, call for a vigilant approach, as subjects with central obesity, hypertension, and smoking could benefit from earlier vaccine boosters or different vaccine schedules.
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Anticuerpos Antivirales , Vacuna BNT162 , SARS-CoV-2 , Anticuerpos Antivirales/sangre , Vacuna BNT162/administración & dosificación , Vacuna BNT162/inmunología , COVID-19/prevención & control , Humanos , Hipertensión/inmunología , Obesidad Abdominal/inmunología , SARS-CoV-2/inmunología , Fumar/inmunologíaRESUMEN
CONTEXT: Chronic glucocorticoid (GC) overexposure, resulting from endogenous Cushing's syndrome (CS) or exogenous GC therapy, causes several adverse outcomes, including persistent central fat accumulation associated with a low-grade inflammation. However, no previous multiomics studies in visceral adipose tissue (VAT) from patients exposed to high levels of unsuppressed GC during active CS or after remission are available yet. OBJECTIVE: To determine the persistent VAT transcriptomic alterations and epigenetic fingerprints induced by chronic hypercortisolism. METHODS: We employed a translational approach combining high-throughput data on endogenous CS patients and a reversible CS mouse model. We performed RNA sequencing and chromatin immunoprecipitation sequencing on histone modifications (H3K4me3, H3K27ac, and H3K27me3) to identify persistent transcriptional and epigenetic signatures in VAT produced during active CS and maintained after remission. RESULTS: VAT dysfunction was associated with low-grade proinflammatory status, macrophage infiltration, and extracellular matrix remodeling. Most notably, chronic hypercortisolism caused a persistent circadian rhythm disruption in VAT through core clock genes modulation. Importantly, changes in the levels of 2 histone modifications associated to gene transcriptional activation (H3K4me3 and H3K27ac) correlated with the observed differences in gene expression during active CS and after CS remission. CONCLUSION: We identified for the first time the persistent transcriptional and epigenetic signatures induced by hypercortisolism in VAT, providing a novel integrated view of molecular components driving the long-term VAT impairment associated with CS.
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Neoplasias de las Glándulas Suprarrenales/complicaciones , Síndrome de Cushing/metabolismo , Glucocorticoides/efectos adversos , Grasa Intraabdominal/inmunología , Obesidad Abdominal/genética , Administración Oral , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/inmunología , Neoplasias de las Glándulas Suprarrenales/orina , Adulto , Animales , Biopsia , Secuenciación de Inmunoprecipitación de Cromatina , Corticosterona/administración & dosificación , Corticosterona/efectos adversos , Estudios Transversales , Síndrome de Cushing/inmunología , Síndrome de Cushing/patología , Modelos Animales de Enfermedad , Epigenoma/efectos de los fármacos , Epigenoma/inmunología , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/metabolismo , Humanos , Hidrocortisona/metabolismo , Hidrocortisona/orina , Inflamación/inducido químicamente , Inflamación/inmunología , Inflamación/metabolismo , Grasa Intraabdominal/metabolismo , Grasa Intraabdominal/patología , Masculino , Ratones , Persona de Mediana Edad , Obesidad Abdominal/inmunología , Obesidad Abdominal/patología , RNA-Seq , Transcriptoma/efectos de los fármacos , Transcriptoma/inmunologíaRESUMEN
Despite evidence that monocyte migration is accentuated by central adiposity, the impact of physical activity (PA) and exercise, particularly in the post-prandial state, on limiting migration are not established. We hypothesised that PA and a single bout of walking exercise would be associated with reduced ex vivo monocyte tethering and migration in middleaged males with central obesity (CO). Objective levels of PA were measured for 7 days in lean males (LE, N=12, mean (SD) age 39 (10) years, waist circumference 81.0 (6.3) cm) and males with CO (N=12, mean (SD) age 40 (9) years, waist circumference 115.3 (13.9) cm), followed by donation of a fasted blood sample. On the same day, CO undertook a bout of walking exercise, before donation of a second fasted blood sample. An ex vivo assay, coupled to flow cytometry, determined tethering and migration of classical, intermediate, and non-classical monocytes. C-C and CXC chemokine receptor (CCR2, CCR5 and CX3CR1) expression were also determined on total and classical monocytes. Monocyte subsets (total, classical, intermediate and CCR2+ monocytes), metabolic (glucose and lipids) and inflammatory (C-reactive protein) markers were greater in CO vs. LE (lower highdensity lipoprotein); however, adjustments for PA mitigated group differences for glucose, lipids, and monocyte subsets. Ex vivo tethering and migration (absolute and relative) of most monocyte subsets was greater in CO vs LE. Relative monocyte tethering and migration was largely not influenced by PA; however, higher PA was associated with reduced absolute migration and tethering of CD16 expressing monocytes in CO. Prior walking had no impact on these variables. These results highlight that regular PA, not single exercise bouts may limit the migration of pro-inflammatory monocytes in CO. These changes may relate to physiological parameters in blood (i.e. number of cells and their adhesion), rather than differences in chemokine receptor expression.
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Ejercicio Físico , Monocitos/citología , Obesidad Abdominal/inmunología , Adulto , Movimiento Celular , Humanos , Masculino , Persona de Mediana Edad , Receptores de Quimiocina , Circunferencia de la CinturaRESUMEN
Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.
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Tejido Adiposo/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Adipoquinas/metabolismo , Tejido Adiposo/inmunología , Animales , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Grasa Intraabdominal/inmunología , Grasa Intraabdominal/metabolismo , Obesidad Abdominal/inmunología , Obesidad Abdominal/metabolismoRESUMEN
Background: Although studies have consistently linked obesity and asthma, the potential influence of visceral obesity on asthma has not been well investigated. Objective: To study the associations of visceral fat area (VFA) and clinical and inflammatory features of asthma and to further explore the effects of VFA on the future risk of asthma exacerbation. Methods: A 12-month prospective cohort study based on the Australasian Severe Asthma Network was designed to observe patients with stable asthma grouped by the median value of VFA. The clinical and inflammatory features of asthma were compared between the low VFA (VFAlow) and high VFA (VFAhigh) groups. Relationships between VFA and clinical and inflammatory features of asthma were analyzed by using correlation analysis. Univariate and multivariable negative binomial regression analyses were performed to investigate the association of VFA with exacerbations within a 12-month follow-up period. Results: The patients in the VFAhigh group were older and had a longer asthma duration. Interleukin (IL) 6 and IL-8 in sputum were higher, whereas fractional exhaled nitric oxide (FeNO) and blood eosinophils were lower in the VFAhigh group. Gender-differentiated correlations of VFA with clinical and inflammatory variables were observed in age, FeNO, immunoglobulin E, blood total white cells and neutrophils, and sputum IL-1ß and IL-8. Furthermore, compared with the VFAlow group, the VFAhigh group was at significantly increased risk of moderate-to-severe exacerbations (adjusted incidence rate ratio [IRR] 1.55 [95% confidence interval {CI}, 1.06-2.28; p = 0.025), severe exacerbations (adjusted IRR 2.25 [95% CI, 1.26-4.04]; p = 0.007), and emergency visits (adjusted IRR 5.33 [95% CI, 1.78-17.16]; p = 0.003). Conclusion: The level of VFA was associated with specific clinical and inflammatory characteristics of asthma. Furthermore, VFA, as an independent risk factor, was associated with an increased risk of exacerbations. It indicated that VFA would provide more potential clinical implications for asthma management.
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Factores de Edad , Asma/epidemiología , Eosinófilos/patología , Inflamación/epidemiología , Obesidad Abdominal/epidemiología , Adulto , Asma/inmunología , China/epidemiología , Estudios de Cohortes , Citocinas/metabolismo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Obesidad Abdominal/inmunología , Estudios ProspectivosRESUMEN
PURPOSE: The association between obesity and autoimmune diseases has been suggested by several previous studies. The objective of our study was to assess the association of abdominal obesity phenotypes with thyroid autoimmunity. MATERIALS AND METHODS: This study was conducted within the framework of a population-based cohort study, Tehran Thyroid Study (TTS) on 4708 subjects without thyroid autoimmunity at baseline. Participants were categorized into four abdominal obesity phenotypes according to waist circumference (WC) and other metabolic syndrome components. Serum concentrations of thyroid peroxidase antibody (TPOAb), free T4 (FT4), thyrotropin (TSH), glucose, and lipid profiles were measured after 3, 6 and 9 years of follow-up. Cox proportional hazard models were used to evaluate associations of different phenotypes with the incidence of thyroid autoimmunity, adjusted for age, sex, FT4, and TSH. RESULTS: Highest and lowest incidence rates of TPOAb positivity were observed among metabolically unhealthy, non-abdominally obese (MUNAO) [8.78 (7.31-10.55) per 1000 person-years of follow-up] and metabolically unhealthy abdominally obese (MUAO) [4.98 (3.88-6.41) per 1000 person-years of follow-up] phenotypes. Considering the metabolically healthy non-abdominal obese (MHNAO) individuals as reference, none of metabolically healthy abdominally obese (MHAO), MUNAO, and MUAO phenotypes were associated with increased risk of developing TPOAb positivity. Compared to individuals with high WC, the incidence rate (95%CI) of TPOAb positivity was higher among those with normal WC: 8.44 (7.13-10.0) vs 5.11 (4.01-6.51) per 1000 person-years, respectively. Higher WC was not associated with incident TPOAb positivity. CONCLUSION: There was no significant association between baseline abdominal obesity phenotype status and development of TPOAb positivity over 9 years of follow-up.
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Autoantígenos/inmunología , Yoduro Peroxidasa/inmunología , Proteínas de Unión a Hierro/inmunología , Síndrome Metabólico , Obesidad Abdominal , Glándula Tiroides/inmunología , Circunferencia de la Cintura , Adulto , Autoanticuerpos/sangre , Femenino , Estudios de Seguimiento , Humanos , Irán , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/clasificación , Síndrome Metabólico/inmunología , Persona de Mediana Edad , Obesidad Abdominal/sangre , Obesidad Abdominal/clasificación , Obesidad Abdominal/inmunología , FenotipoAsunto(s)
Complemento C3/metabolismo , Complemento C4/metabolismo , Inmunoglobulina E/sangre , Longevidad , Síndrome Metabólico/sangre , Obesidad Abdominal/sangre , Inmunidad Adaptativa , Anciano de 80 o más Años , Femenino , Humanos , Inmunidad Innata , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/inmunología , Obesidad Abdominal/complicaciones , Obesidad Abdominal/inmunologíaRESUMEN
BACKGROUND: The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity. METHODS: This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses. DISCUSSION: Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.
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Suplementos Dietéticos , Inflamación/diagnóstico , Luteína/administración & dosificación , Obesidad Abdominal/dietoterapia , Adolescente , Adulto , Biomarcadores/sangre , Glucemia/análisis , Glucemia/metabolismo , Método Doble Ciego , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Inflamación/prevención & control , Metabolismo de los Lípidos/inmunología , Lípidos/sangre , Luteína/sangre , Masculino , Persona de Mediana Edad , Obesidad Abdominal/sangre , Obesidad Abdominal/inmunología , Obesidad Abdominal/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Resultado del Tratamiento , Circunferencia de la Cintura , Adulto JovenRESUMEN
BACKGROUND: Proinflammatory genes are highly expressed in several metabolic disorders associated with obesity. But it is not clarified whether gene expression levels and downstream inflammatory markers are related to the metabolic state or the presence of obesity. Hence, the present study aimed to compare Toll-Like Receptor 2 (TLR2), Myeloid Differentiation Factor 88 (MyD88), and NFĸB mRNA expression levels between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. RESULTS: We compared mRNA expression levels of the genes as well as serum FFAs and IL-1ß in MUAO (n = 36) and MHAO (n = 34) groups. Serum FBS, TG, and HDL-C in addition to systolic and diastolic blood pressure were significantly higher in MUAO than MHAO groups (p < 0.05). The odds of MUAO was significantly decreased with high HDL-C (OR = 0.22, 95%CI: 0.08-0.63) and increased with high FBS (OR = 7.04, 95%CI: 1.42-34.69) and TG (OR = 30.55, 95%CI: 7.48-60.67). There were no significant differences in proinflammatory genes as well as serum FFAs and IL-1ß between the two groups. No associations were found between the genes expression and serum markers. However, NFĸB expression was significantly correlated with TLR2 and MyD88 (r = 0.747; p < 0.001). Significant correlations were also noticed between TLR2 and MyD88 expression as well as between serum FFAs and IL-1ß in each group (p < 0.001). CONCLUSION: Serum concentration of IL-1ß, FFAs, and mRNA expression levels of TLR2, MyD88, and NFĸB may be resulted from abdominal obesity and not be related to the presence or absence of metabolic health.
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Ácidos Grasos no Esterificados/sangre , Interleucina-1beta/sangre , Enfermedades Metabólicas/inmunología , Factor 88 de Diferenciación Mieloide/genética , FN-kappa B/genética , Obesidad Abdominal/inmunología , Receptor Toll-Like 2/genética , Adulto , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Inflamación/genética , Masculino , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population. OBJECTIVES: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD. METHODS: Cases with biopsy-proven NAFLD and HIV monoinfection were age and sex-matched to HIV-positive and HIV-negative controls. Markers of bacterial translocation [lipopolysaccharide-binding protein (LBP), bacterial DNA and lipopolysaccharide (LPS)], adipose tissue dysfunction (leptin, adiponectin) and monocyte activation (sCD14 and sCD163) were measured by ELISA. Hepatic patterns of macrophage activation were explored with immunohistochemistry. 16âs rRNA sequencing was performed with stool. RESULTS: Thirty-three cases were included (≥F2 fibrosis nâ=â16), matched to HIV-positive (nâ=â29) and HIV-negative (nâ=â17) controls. Cases with NAFLD were more obese (BMI 31.0â±â4.4 vs. 24.1â±â2.8âkg/m, Pâ<â0.001) and had significantly increased levels of sCD14, sCD163 and higher leptin to adiponectin ratio vs. HIV-positive controls. Cases with ≥F2 versesâ<âF2 fibrosis had increased sCD14 (1.4â±â0.4 vs. 1.1â±â0.3âµg/ml, Pâ=â0.023) and sCD163 (1.0â±â0.3 vs. 0.8â±â0.3âµg/ml, Pâ=â0.060), which correlated with waist circumference (sCD14 Pâ=â0.022, sCD163 Pâ=â0.011). Immunohistochemistry showed increased hepatic portal macrophage clusters in patients with fibrosis. No markers of bacterial translocation or changes to the microbiome were associated with NAFLD or fibrosis. CONCLUSION: NAFLD fibrosis stage in HIV monoinfected patients is associated with monocyte activation in the context of obesity, which may be independent of bacterial translocation and gut microbiome.
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Traslocación Bacteriana/fisiología , Infecciones por Bacteroidaceae/patología , Microbioma Gastrointestinal/inmunología , Seropositividad para VIH/inmunología , Cirrosis Hepática/patología , Activación de Macrófagos/fisiología , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad Abdominal/inmunología , Adulto , Infecciones por Bacteroidaceae/inmunología , Disbiosis/virología , Heces/microbiología , Femenino , Seropositividad para VIH/fisiopatología , Humanos , Inmunohistoquímica , Hígado/patología , Cirrosis Hepática/inmunología , Cirrosis Hepática/microbiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/microbiología , Obesidad Abdominal/microbiología , Prevotella/aislamiento & purificación , Estudios Prospectivos , ARN Ribosómico 16S , Reino UnidoRESUMEN
The global obesity epidemic is the subject of an immense, diversely specialized research effort. An evolutionary analysis reveals connections among disparate findings, starting with two well-documented facts: Obesity-associated illnesses (e.g., type-2 diabetes and cardiovascular disease), are especially common in: (i) adults with abdominal obesity, especially enlargement of visceral adipose tissue (VAT), a tissue with important immune functions; and (ii) individuals with poor fetal nutrition whose nutritional input increases later in life. I hypothesize that selection favored the evolution of increased lifelong investment in VAT in individuals likely to suffer lifelong malnutrition because of its importance in fighting intraabdominal infections. Then, when increased nutrition violates the adaptive fetal prediction of lifelong nutritional deficit, preferential VAT investment could contribute to abdominal obesity and chronic inflammatory disease. VAT prioritization may help explain several patterns of nutrition-related disease: the paradoxical increase of chronic disease with increased food availability in recently urbanized and migrant populations; correlations between poor fetal nutrition, improved childhood (catch-up) growth, and adult metabolic syndrome; and survival differences between children with marasmus and kwashiorkor malnutrition. Fats and sugars can aggravate chronic inflammation via effects on intestinal bacteria regulating gut permeability to visceral pathogens. The extremes in a nutrition-sensitive trade-off between visceral (immune-function) vs. subcutaneous (body shape) adiposity may have been favored by selection in highly stratified premedicine societies. Altered adipose allocation in populations with long histories of social stratification and malnutrition may be the result of genetic accommodation of developmental responses to poor maternal/fetal conditions, increasing their vulnerability to inflammatory disease.
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Evolución Biológica , Grasa Intraabdominal/inmunología , Obesidad Abdominal/inmunología , Animales , Grasas de la Dieta/efectos adversos , Trastornos Nutricionales en el Feto , Jarabe de Maíz Alto en Fructosa/efectos adversos , Humanos , Inflamación/etiología , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiologíaRESUMEN
BACKGROUND: Abdominal obesity is characterized by low-grade inflammation and plays a central role in the development of type 2 diabetes and cardiovascular diseases. Dietary factors can influence low-grade inflammation and affect adipose tissue function. AIM: To investigate the separate and combined effects of whey protein and cereal fiber on inflammatory markers and adipose tissue gene expression in abdominal obesity. METHODS: We performed a 12-week, double-blind, randomized controlled dietary intervention in 65 adults with abdominal obesity. The participants were randomized to 4 groups using a 2 × 2 factorial design; they received either 60 g/day of whey protein or maltodextrin in combination with high-fiber wheat bran products (30 g fiber/day) or low-fiber refined wheat products (10 g fiber/day). Plasma concentrations of tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), interleukin 1 receptor antagonist (IL-1Ra), and adiponectin were measured before and after intervention. Changes in gene expression related to inflammation, insulin signaling, and lipid metabolism were measured in abdominal subcutaneous adipose tissue. RESULTS: After intervention, TNF-α was reduced for both high-fiber groups compared with baseline, but did not significantly differ from the low-fiber groups. There were no differences in fasting or postprandial inflammatory markers between the groups. The relative gene expression of ribosomal protein S6 kinase B1 (S6K1) was increased after whey protein compared with maltodextrin consumption. CONCLUSION: Intake of whey protein in combination with high cereal fiber content did not differentially affect low-grade inflammation or adipose tissue gene expression compared with maltodextrin and low fiber content in individuals with abdominal obesity.
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Tejido Adiposo/inmunología , Fibras de la Dieta/metabolismo , Obesidad Abdominal/dietoterapia , Proteína de Suero de Leche/metabolismo , Adiponectina/genética , Adiponectina/inmunología , Adulto , Proteína C-Reactiva/genética , Proteína C-Reactiva/inmunología , Quimiocina CCL2/genética , Quimiocina CCL2/inmunología , Fibras de la Dieta/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/genética , Obesidad Abdominal/inmunología , Periodo Posprandial/inmunología , Proteína de Suero de Leche/administración & dosificaciónRESUMEN
OBJECTIVE: It has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in hypertension. In particular, Th1 and Th 17 lymphocytes may contribute to the progression of hypertension and microvascular damage while T-regulatory (Treg) lymphocytes seem to be protective in this regard. However, no data is available about patients with severe obesity, in which pronounced microvascular alterations were observed. DESIGN AND METHODS: We have investigated 32 severely obese patients undergoing bariatric surgery, as well as 24 normotensive lean subjects and 12 hypertensive lean subjects undergoing an elective surgical intervention. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry in order to assess T-effector and Treg lymphocytes. RESULTS: A marked reduction of several Treg subpopulations was observed in obese patients compared with controls, together with an increased in CD4+ effector memory T-effector cells. CONCLUSION: In severely obese patients, Treg lymphocytes are clearly reduced and CD4+ effector memory cells are increased. It may be hypothesized that they might contribute to the development of marked microvascular alterations previously observed in these patients.
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Cirugía Bariátrica , Memoria Inmunológica , Obesidad Abdominal , Linfocitos T Reguladores , Células Th17 , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/sangre , Obesidad Abdominal/inmunología , Obesidad Abdominal/cirugía , Índice de Severidad de la Enfermedad , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/inmunología , Células Th17/metabolismoRESUMEN
BACKGROUND: Understanding the extent to which visceral and subcutaneous body fat are associated with markers of nutrition and inflammation in patients on dialysis therapy could shed light on the obesity paradox and the biology of subcutaneous fat. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 609 adults receiving hemodialysis who participated in the ACTIVE/ADIPOSE Study. PREDICTORS: Body mass index (BMI), waist circumference, and bioelectrical impedance spectroscopy-derived estimates of percent body fat. OUTCOMES: C-Reactive protein (CRP), interleukin 6 (IL-6), prealbumin, albumin, leptin, and adiponectin concentrations. MEASUREMENTS: We performed linear regression analyses to examine the extent to which proxies of visceral and subcutaneous fat were associated with inflammation, nutrition, and adiposity-related hormones. RESULTS: BMI was directly associated with markers of inflammation (standardized estimate for ln[CRP in mg/L]: 0.30 [95% CI, 0.22-0.38] per 10kg/m2; for ln[IL-6 in pg/mL]: 0.10 [95% CI, 0.02-0.18] per 10kg/m2), but was not associated with markers of nutrition. BMI was also inversely associated with adiponectin and directly associated with leptin. With waist circumference and percent body fat (as a proxy of visceral and subcutaneous fat, respectively) modeled together, waist circumference was associated with markers of inflammation (standardized estimate for ln[CRP in mg/L]: 0.21 [95% CI, 0.09-0.34] per 10cm; for ln[IL-6 in pg/mL]: 0.18 [95% CI, 0.07-0.29] per 10cm), whereas percent body fat was not associated with CRP (standardized estimate for ln[CRP in mg/L]: 0.03 [95% CI, -0.10 to 0.15] per 1%) and was inversely associated with IL-6 (standardized estimate for ln[IL-6 in pg/mL]: -0.15 [95% CI, -0.27 to -0.02] per 1%). In addition, waist circumference was inversely associated with prealbumin and albumin (standardized estimates of -0.12 [95% CI, -0.23 to -0.02] mg/dL per 10cm and -0.17 [95% CI, -0.28 to -0.06] g/dL per 10cm, respectively), and percent body fat was directly associated with prealbumin and albumin (0.20 [95% CI, 0.07-0.32] mg/dL and 0.15 [95% CI, 0.02-0.28] g/dL per 1%, respectively). Higher waist circumference was associated indirectly with adiponectin and directly with leptin concentrations. LIMITATIONS: Although the observed associations implicate visceral fat as the cause of inflammation, it cannot be determined in this cross-sectional study. CONCLUSIONS: Proxies of visceral and subcutaneous fat appear to have opposing associations with biomarkers of inflammation and nutrition. Subcutaneous fat may be an indicator of nutritional status, and visceral fat, an indicator of inflammation.
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Fallo Renal Crónico/metabolismo , Estado Nutricional , Obesidad Abdominal/metabolismo , Adiponectina/metabolismo , Tejido Adiposo , Adulto , Anciano , Composición Corporal , Índice de Masa Corporal , Proteína C-Reactiva/inmunología , Estudios Transversales , Espectroscopía Dieléctrica , Femenino , Humanos , Inflamación , Interleucina-6/inmunología , Grasa Intraabdominal , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/terapia , Leptina/metabolismo , Modelos Lineales , Masculino , Persona de Mediana Edad , Obesidad/inmunología , Obesidad/metabolismo , Obesidad Abdominal/complicaciones , Obesidad Abdominal/inmunología , Prealbúmina/metabolismo , Diálisis Renal , Albúmina Sérica/metabolismo , Grasa Subcutánea , Circunferencia de la CinturaRESUMEN
OBJECTIVES: The underlying mechanism of atherosclerosis and visceral obesity remains unknown.The purpose of this study was to test the hypothesis that atherosclerosis and visceral obesity are caused by an immune response to native plasma lipoproteins, and the atherogenic and adipogenic effects of the antibodies to native lipoproteins stem from the androgen deficiency that is created. METHODS: Wistar rats were immunized with native human (nh) low-density (LDL) or high-density lipoproteins (HDL). Visceral fat, aortic wall structure, and testosterone levels were studied. RESULTS: Immunization with nhLDL or nhHDL induced in rats increased visceral abdominal fat and perivascular adipose tissue volume, the appearance of epicardial fat, and atherosclerosis-like changes in the aortic wall: accumulation of leucocytes, destruction of the intima, and disruption of the media structure. Immunized rats produced antibodies to native plasma lipoproteins, while there was no difference between immunized and adjuvant-injected rats with regard to the level of antibodies to oxidized LDL. The immune response to nhHDL caused testosterone disturbances, but it is not associated with visceral obesity and atherosclerosis. CONCLUSION: The immune response to native lipoproteins is atherogenic and adipogenic and testosterone is not involved in the atherogenic and adipogenic effects of antibodies to lipoproteins.
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Aorta/inmunología , Aterosclerosis/inmunología , Inmunidad Celular/inmunología , Lipoproteínas/toxicidad , Obesidad Abdominal/inmunología , Testosterona/inmunología , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aterosclerosis/sangre , Aterosclerosis/inducido químicamente , Humanos , Inmunidad Celular/efectos de los fármacos , Masculino , Obesidad Abdominal/sangre , Obesidad Abdominal/inducido químicamente , Ratas , Ratas Wistar , Testosterona/sangreRESUMEN
OBJECTIVES: This study aimed to compare serum free fatty acids (FFAs) and lipopolysaccharide-binding protein (LBP) between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. We also examined the association between serum FFAs and LBP in the participants. METHODS: In this age-matched and gender-matched case-control study, 164 abdominally obese subjects were recruited from June to November 2015 in the northwest of Iran. Demographic data, dietary intake, body composition, anthropometric indices and physical activity (PA) were assessed. Basal blood samples were collected to determine serum metabolic parameters, FFAs and LBP. Abdominal obesity was defined as having waist circumference ≥95 cm. Those with three or more metabolic alterations were defined as MUAO and those having two or less were classified as MHAO. Data were analysed using SPSS V.17.0. RESULTS: There were no significant differences in dietary intake, anthropometric indices, body composition and PA between the two groups. The odds of MUAO significantly increased by increments in serum fasting blood sugar (OR 3.79, 95% CI 2.25 to 6.40), triglycerides (OR 1.10, 95% CI 1.05 to 1.15), systolic blood pressure (OR 1.02, 95% CI 1.00 to 1.04) and diastolic blood pressure (OR 1.03, 95% CI 1.01 to 1.06) and decreased by increase in serum high-density lipoprotein cholesterol (OR 0.32, 95% CI 0.20 to 0.52). The levels of LBP and FFAs showed no significant differences between the two groups. However, significant correlations were found between LBP and FFAs in pooled population (r=0.712; p<0.001) as well as in cases (r=0.717; p<0.001) and controls (r=0.704; p<0.001). Neither FFAs nor LBP were significantly correlated with dietary intake or metabolic parameters (p>0.05). CONCLUSION: The results indicated that serum LBP and FFAs are highly correlated both in MHAO and MUAO states. In addition, the levels of LBP and FFAs seem to be more related to abdominal obesity than to the presence or absence of metabolic health.
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Proteínas Portadoras/sangre , Endotoxemia/sangre , Ácidos Grasos no Esterificados/sangre , Lipoproteínas HDL/sangre , Glicoproteínas de Membrana/sangre , Obesidad Abdominal/sangre , Triglicéridos/sangre , Proteínas de Fase Aguda , Adulto , Estudios de Casos y Controles , Endotoxemia/inmunología , Endotoxemia/fisiopatología , Ejercicio Físico , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Obesidad Abdominal/inmunología , Obesidad Abdominal/fisiopatología , Prevalencia , Factores de Riesgo , Circunferencia de la Cintura , Adulto JovenRESUMEN
Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively. In a subset of 30 patients, circulating levels of IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TGF-ß, and cortisol were measured. Incidences of postoperative complications were prospectively recorded. In the study cohort, 51% of patients were viscerally obese, 40.7% had MetSyn, and 33.6% were hyperglycemic. Viscerally obese and MetSyn-positive patients demonstrated greater postoperative CRP levels and CRP:albumin levels on day 7 and day 14 compared with nonobese and MetSyn-negative patients (P < 0.05). Higher postoperative circulating levels of cortisol were observed in the viscerally obese and hyperglycemic patients compared to nonobese and normoglycemic patients. No association was observed between visceral obesity, MetSyn or hyperglycemia, and postoperative cytokine profile. Viscerally obese patients had an increased overall incidence of postoperative complications compared to nonobese patients (67.2% vs. 47.5%, P = 0.031) on univariate but not multivariate analysis (P = 0.078) and visceral obesity was not associated with an increased incidence of specific complications. Visceral obesity, MetSyn, and hyperglycemia are prevalent in patients undergoing major upper gastrointestinal resection and are associated with an exaggerated acute-phase inflammatory response postoperatively. Further research is warranted to determine whether this association is directly causal.
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Adenocarcinoma/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Síndrome Metabólico/complicaciones , Obesidad Abdominal/complicaciones , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Citocinas/sangre , Femenino , Humanos , Hidrocortisona/sangre , Incidencia , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/inmunología , Persona de Mediana Edad , Obesidad Abdominal/sangre , Obesidad Abdominal/inmunología , Complicaciones Posoperatorias/epidemiología , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Prospectivos , Estudios Retrospectivos , Albúmina Sérica/análisis , Resultado del TratamientoRESUMEN
OBJECTIVE: The C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are important disease activity biomarkers in rheumatoid arthritis (RA). This study aimed to determine to what extent obesity biases these biomarkers. METHODS: Body mass index (BMI) associations with CRP level and ESR were assessed in 2 RA cohorts: the cross-sectional Body Composition (BC) cohort (n = 451), including whole-body dual x-ray absorptiometry measures of fat mass index; and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA) registry (n = 1,652), using multivariable models stratified by sex. For comparison, associations were evaluated in the general population using the National Health and Nutrition Examination Survey. RESULTS: Among women with RA and in the general population, greater BMI was associated with greater CRP levels, especially among women with severe obesity (P < 0.001 for BMI ≥35 kg/m2 versus 20-25 kg/m2 ). This association remained after adjustment for joint counts and patient global health scores (P < 0.001 in BC and P < 0.01 in VARA), but was attenuated after adjustment for fat mass index (P = 0.17). Positive associations between BMI and ESR in women were more modest. In men with RA, lower BMI was associated with higher CRP levels and ESR, contrasting with positive associations among men in the general population. CONCLUSION: Obesity is associated with higher CRP levels and ESR in women with RA. This association is related to fat mass and not RA disease activity. Low BMI is associated with higher CRP levels in men with RA; this unexpected finding remains incompletely explained but likely is not a direct effect of adiposity.
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Adiposidad , Artritis Reumatoide/inmunología , Proteína C-Reactiva/análisis , Mediadores de Inflamación/sangre , Obesidad Abdominal/fisiopatología , Absorciometría de Fotón , Adulto , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Biomarcadores/sangre , Sedimentación Sanguínea , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Encuestas Nutricionales , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Obesidad Abdominal/inmunología , Sistema de Registros , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The renin-angiotensin system has a pivotal role in the pathophysiology of visceral obesity. Angiotensin II type 1 receptor (AT1R) is a major player in the signal transduction of the renin-angiotensin system, and the overactivation of this signaling contributes to the progression of visceral obesity. We have shown that the AT1R-associated protein (ATRAP) promotes AT1R internalization from the cell surface into cytoplasm along with the suppression of overactivation of tissue AT1R signaling. In this study, we examined whether the enhancement of adipose ATRAP expression could efficiently prevent diet-induced visceral obesity and insulin resistance. METHODS AND RESULTS: We generated adipocyte-specific ATRAP transgenic mice using a 5.4-kb adiponectin promoter, and transgenic mice and littermate control mice were fed either a low- or high-fat diet for 10 weeks. Although the physiological phenotypes of the transgenic and control mice fed a low-fat diet were comparable, the transgenic mice exhibited significant protection against high-fat diet-induced adiposity, adipocyte hypertrophy, and insulin resistance concomitant with an attenuation of adipose inflammation, macrophage infiltration, and adipokine dysregulation. In addition, when mice were fed a high-fat diet, the adipose expression of glucose transporter type 4 was significantly elevated and the level of adipose phospho-p38 mitogen-activated protein kinase was significantly attenuated in the transgenic mice compared with control mice. CONCLUSIONS: Results presented in this study suggested that the enhancement in adipose ATRAP plays a protective role against the development of diet-induced visceral obesity and insulin resistance through improvement of adipose inflammation and function via the suppression of overactivation of adipose AT1R signaling. Consequently, adipose tissue ATRAP is suggested to be an effective therapeutic target for the treatment of visceral obesity.