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1.
Int Heart J ; 62(5): 1091-1095, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544988

RESUMO

This is the first study to evaluate directly visceral fat area (VFA) using a visceral fat (VF) meter by the abdominal bioelectrical impedance analysis (A-BIA) method in obstructive sleep apnea (OSA) patients diagnosed with polysomnography (PSG). The purpose of this study is to clarify (1) whether VFA measurement using a VF meter by the A-BIA method is possible even in a private clinic without burdening patients and staff and (2) how much VFA affects OSA compared to body mass index (BMI). Even without a computed tomography scan, which is the gold standard for VFA measurement, a VF meter could analyze patients by the A-BIA method and easily measure VFA. Therefore, it could be used safely even in a private sleep clinic, with very little burden on the patients and the medical staff. We investigated the association between OSA and VFA in 133 OSA patients. Multiple regression analysis revealed that VFA (ß = 0.28; P = 0.020) was a stronger coexisting factor for OSA than age, male gender, or BMI (ß = 0.26; P = 0.032) in all OSA patients. In the OSA patients with VF accumulation, only VFA was a significant component of OSA severity (ß = 0.36; P = 0.006). The A-BIA method instrument could become a useful device for the evaluation of VF accumulation in OSA patients in private sleep clinics. VF accumulation should be recognized as an important risk factor as well as a known risk factor for OSA.


Assuntos
Impedância Elétrica/efeitos adversos , Gordura Intra-Abdominal/diagnóstico por imagem , Polissonografia/métodos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Composição Corporal/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Gordura Intra-Abdominal/crescimento & desenvolvimento , Gordura Intra-Abdominal/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico
2.
Front Endocrinol (Lausanne) ; 12: 726967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484128

RESUMO

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.


Assuntos
COVID-19/metabolismo , Cardiomiopatias/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/complicações , COVID-19/imunologia , Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Inflamação , Gordura Intra-Abdominal/patologia , Obesidade/complicações , Obesidade/imunologia , Obesidade/patologia , Pericárdio , Prognóstico , SARS-CoV-2/metabolismo , Serina Endopeptidases/metabolismo
3.
Nutrients ; 13(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201185

RESUMO

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-ß levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.


Assuntos
Glicemia/metabolismo , Dieta Rica em Proteínas , Inflamação/sangue , Gordura Intra-Abdominal/patologia , Treinamento de Força , Adipócitos/patologia , Animais , Tamanho Celular , Dieta , Epididimo/patologia , Glutationa/metabolismo , Resistência à Insulina , Masculino , Tamanho do Órgão , Ratos Wistar , Ganho de Peso
4.
Int J Biochem Cell Biol ; 137: 106031, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34175459

RESUMO

Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, that is, glucose uptake. Numerous conditions lead to IR, including epigenetic components. Epigenetic modifications, associated with obesity and IR are one of the main mechanisms leading to IR pathogenesis. The adipose tissue samples (subcutaneous (SAT) and visceral (VAT)) were collected during abdominal surgery from 40 patients of a wide range of BMI, age, and insulin resistance ratios (F = 9, M = 31). IR was induced in 3T3-L1 adipocytes and human adipocytes collected from SAT and VAT of healthy subjects. Global and site-specific histone modifications (H3K4me3 and H3K9/14ac) were determined. We found lower histone modifications in adipose tissue of IR patients. Furthermore, numerous genes regulating insulin action (PPARG, SLC2A4, ADIPOQ) were differently marked by histone methylation and acetylation. Moreover, we noticed that epigenetic changes appear as soon as 72 h following IR induction. The epigenetic changes appeared to be mediated through the SIRT family. Based on obtained results, the histone marks related to insulin resistance mostly concerned PPARG and SLC2A4 genes. Furthermore, our results proved a vital role of the SIRT family in insulin action and IR pathogenesis.


Assuntos
Adipogenia , Epigênese Genética , Histonas/genética , Resistência à Insulina , Insulina/metabolismo , Gordura Intra-Abdominal/patologia , Gordura Subcutânea/patologia , Células 3T3-L1 , Adulto , Animais , Estudos de Casos e Controles , Metilação de DNA , Humanos , Insulina/genética , Gordura Intra-Abdominal/metabolismo , Camundongos , Pessoa de Meia-Idade , Gordura Subcutânea/metabolismo
5.
PLoS One ; 16(5): e0251822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33989346

RESUMO

BACKGROUND: Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients. METHODS: Plasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed. RESULTS: Plasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls. CONCLUSION: Our study does not support a role for Nrg4 in the pathophysiology of human NAFLD.


Assuntos
Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Neurregulinas/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adipocinas/sangue , Tecido Adiposo Marrom/metabolismo , Adulto , Índice de Massa Corporal , Progressão da Doença , Feminino , Humanos , Interferon gama/sangue , Interferon gama/genética , Interleucina-6/sangue , Interleucina-6/genética , Gordura Intra-Abdominal/patologia , Lipogênese/genética , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Neurregulinas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética
6.
Adipocyte ; 10(1): 285-292, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34014795

RESUMO

Although much is known about how adipose tissue affects the development of clear cell renal carcinoma (ccRCC), little information is available for the utility of sex-specific abdominal visceral fat composition as a predictor of clear cell renal carcinoma (ccRCC) T stage. We conducted CT-based sex-specific abdominal fat measurements in ccRCC patients to assess whether VFA distribution could predict the ccRCC T stage. In total, 253 patients (182 males and 71 females) from our hospital with pathologically confirmed ccRCC (178 low T-stage and 75 high T-stage) were retrospectively reviewed for the present study. Computed tomography (CT) scans were assessed using ImageJ to differentiate between the visceral and subcutaneous fat areas (VFA and SFA), after which the relative VFA (rVFA) and total fat area (TFA) were computed. The relationships between these fat area-related variables, patient age, sex, and BMI, and ccRCC T stage were then evaluated through univariate and multivariate logistic regression analysis to clarify the association between general or sex-specific abdominal visceral fat and T stage. Following adjustment for age, males with high T stage ccRCC exhibited an increased rVFA as compared to males with low T stage ccRCC, with the same relationship being observed among females. This association between rVFA and high T stage was confirmed through both univariate and multivariate models. As thus, sex-specific visceral fat composition is a reliable independent predictor that can identify both male and female patients with high T stage ccRCC.


Assuntos
Carcinoma de Células Renais/patologia , Gordura Intra-Abdominal/patologia , Neoplasias Renais/patologia , Gordura Subcutânea Abdominal/patologia , Tomografia Computadorizada por Raios X , Tecido Adiposo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores Sexuais
7.
FASEB J ; 35(6): e21650, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33993539

RESUMO

Mesenchymal stem cells from healthy adipose tissue are adipocytes progenitors with immunosuppressive potential that are used for years in cell therapy. Whether adipose stem cells (ASC) may prevent inflammation in early obesity is not known. To address this question, we performed a kinetic study of high-fat (HF) diet induced obesity in mice to follow the immune regulating functions of adipose stem cells (ASC) isolated from the subcutaneous (SAT) and the visceral adipose tissue (VAT). Our results show that, early in obesity and before inflammation was detected, HF diet durably and differently activated ASC from SAT and VAT. Subcutaneous ASC from HF-fed mice strongly inhibited the proliferation of activated T lymphocytes, whereas visceral ASC selectively inhibited TNFα expression by macrophages and simultaneously released higher concentrations of IL6. These depot specific differences may contribute to the low-grade inflammation that develops with obesity in VAT while inflammation in SAT is delayed. The mechanisms involved differ from those already described for naïve cells activation with inflammatory cytokines and probably engaged metabolic activation. These results evidence that adipose stem cells are metabolic sensors acquiring an obesity-primed immunocompetent state in answer to depot-specific intrinsic features with overnutrition, placing these cells ahead of inflammation in the local dialog with immune cells.


Assuntos
Tecido Adiposo/imunologia , Inflamação/imunologia , Gordura Intra-Abdominal/imunologia , Células-Tronco Mesenquimais/imunologia , Obesidade/fisiopatologia , Gordura Subcutânea/imunologia , Linfócitos T/imunologia , Tecido Adiposo/patologia , Animais , Inflamação/patologia , Gordura Intra-Abdominal/patologia , Ativação Linfocitária , Masculino , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Gordura Subcutânea/patologia , Linfócitos T/patologia
8.
Obesity (Silver Spring) ; 29(6): 976-984, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33943025

RESUMO

OBJECTIVE: Morphological alterations including adipocyte hypertrophy and fibrosis deposition are important surrogate markers of visceral adipose tissue function, but the relationships between these morphological changes and type 2 diabetes mellitus (T2DM) and impaired insulin sensitivity are poorly defined. METHODS: Omental adipose tissue was obtained from 66 individuals with obesity but without T2DM (OB group), 93 individuals with both obesity and T2DM (T2DM group), and 15 individuals with normal BMI and normal glucose tolerance (NGT group). Adipocyte diameter and volume were measured through pathological section analysis. Pericellular and perilobular fibrosis was determined through picrosirius red staining and immunochemistry, while fibrosis-related genes were tested through gene expression and hydroxyproline content. RESULTS: Compared with the NGT and OB groups, individuals from the T2DM group displayed increased adipocyte diameter and volume levels. Increased adipocyte size (diameter and volume) was positively associated with hyperglycemia and insulin resistance and inversely correlated with insulin sensitivity (using the Matsuda whole-body insulin sensitivity index assessment of insulin sensitivity) and ß-cell function (disposition index 30 and disposition index 120). The fibrosis levels of the OB group were the highest out of the three groups, whereas the fibrosis levels of T2DM individuals were lower than the OB group but higher than the NGT group. Although fibrosis was negatively correlated with T2DM, fibrosis deposition was not remarkably associated with impaired systemic insulin sensitivity and glucose metabolism. CONCLUSIONS: Compared with fibrosis deposition, adipocyte hypertrophy is more closely associated with T2DM and impaired systemic insulin sensitivity.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Gordura Intra-Abdominal/patologia , Obesidade/epidemiologia , Omento/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Fibrose/complicações , Fibrose/epidemiologia , Fibrose/metabolismo , Humanos , Hipertrofia/complicações , Hipertrofia/epidemiologia , Hipertrofia/metabolismo , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Omento/patologia
9.
Obesity (Silver Spring) ; 29(6): 1014-1021, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33893721

RESUMO

OBJECTIVE: This study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat. METHODS: The day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1-14 C]triolein-labeled very low-density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U-13 C]palmitate infusion/bolus [9,10-3 H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL-triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl-CoA synthetase, diacylglycerol acetyl-transferase, and glycerol-3-phosphate acyltransferase activities. RESULTS: Storage of VLDL-TG and FFA-palmitate in UBSQ and VAT was not different. Plasma palmitate concentrations correlated with palmitate storage rates in UBSQ and VAT (r = 0.46, P = 0.02 and r = 0.46, P = 0.02, respectively). In VAT, VLDL-TG storage was correlated with VLDL concentrations (r = 0.53, P < 0.009) and LPL (r = 0.42, P < 0.05). In UBSQ, VLDL-TG storage was correlated with LPL (r = 0.42, P < 0.05). CD36, acyl-CoA synthetase, glycerol-3-phosphate acyltransferase, and diacylglycerol acetyl-transferase were not correlated with VLDL-TG or palmitate storage. CONCLUSIONS: Adipose storage of VLDL-TG is predicted by VLDL-TG concentrations and LPL; FFA concentrations predict direct adipose tissue FFA storage rates.


Assuntos
Ácidos Graxos/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade Mórbida/metabolismo , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adolescente , Adulto , Cirurgia Bariátrica , Ácidos Graxos não Esterificados/metabolismo , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Lipoproteínas VLDL/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Gordura Subcutânea/patologia , Triglicerídeos/metabolismo , Adulto Jovem
10.
Aging (Albany NY) ; 13(8): 11774-11785, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33883304

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, accounting for 50-70% of anovulatory infertility cases. However, the etiology of PCOS at the molecular level remains unclear. Here, bioinformatics analysis was performed to identify differentially expressed genes (DEGs) between adipose tissue of PCOS patients and matched tissues from non-hyperandrogenic women. RT-qPCR, western blot, cell counting kit-8 (CCK-8), EdU (5-Ethynyl-2'-deoxyuridine) staining, LC3 staining, ROS (reactive oxygen species) detection, and apoptosis assays were conducted to explore the effects of sestrin 1 on KGN human granulosa-like tumor cells. Bioinformatics analysis indicated that DEGs in adipose tissue from PCOS patients were enriched in the p53 signaling pathway. Moreover, sestrin 1 was identified as a major target of the p53 gene. Downregulation of sestrin 1 inhibited proliferation of KGN cells by inhibiting autophagy. Additionally, sestrin 1 downregulation increased ROS generation and promoted apoptosis in KGN cells. By contrast, overexpression of sestrin 1 increased cell viability by increasing autophagy in KGN cells. Together, these results suggest that downregulation of sestrin 1 may be a potential novel treatment strategy for PCOS.


Assuntos
Autofagia/genética , Proteínas de Ciclo Celular/genética , Proteínas de Choque Térmico/genética , Gordura Intra-Abdominal/patologia , Síndrome do Ovário Policístico/genética , Animais , Apoptose/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Biologia Computacional , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Células da Granulosa/patologia , Voluntários Saudáveis , Humanos , Omento , Síndrome do Ovário Policístico/patologia , Ratos , Espécies Reativas de Oxigênio , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
11.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809055

RESUMO

Mineralocorticoid receptor (MR) expression is increased in the adipose tissue (AT) of obese patients and animals. We previously demonstrated that adipocyte-MR overexpression in mice (Adipo-MROE mice) is associated with metabolic alterations. Moreover, we showed that MR regulates mitochondrial dysfunction and cellular senescence in the visceral AT of obese db/db mice. Our hypothesis is that adipocyte-MR overactivation triggers mitochondrial dysfunction and cellular senescence, through increased mitochondrial oxidative stress (OS). Using the Adipo-MROE mice with conditional adipocyte-MR expression, we evaluated the specific effects of adipocyte-MR on global and mitochondrial OS, as well as on OS-induced damage. Mitochondrial function was assessed by high throughput respirometry. Molecular mechanisms were probed in AT focusing on mitochondrial quality control and senescence markers. Adipo-MROE mice exhibited increased mitochondrial OS and altered mitochondrial respiration, associated with reduced biogenesis and increased fission. This was associated with OS-induced DNA-damage and AT premature senescence. In conclusion, targeted adipocyte-MR overexpression leads to an imbalance in mitochondrial dynamics and regeneration, to mitochondrial dysfunction and to ageing in visceral AT. These data bring new insights into the MR-dependent AT dysfunction in obesity.


Assuntos
Gordura Intra-Abdominal/metabolismo , Obesidade/genética , Estresse Oxidativo/genética , Receptores de Mineralocorticoides/genética , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Senescência Celular/genética , Humanos , Gordura Intra-Abdominal/patologia , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Obesidade/metabolismo , Obesidade/patologia
12.
BMC Gastroenterol ; 21(1): 170, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849437

RESUMO

BACKGROUND: Causes of non-alcoholic fatty liver disease and its progression include visceral fat accumulation and loss of muscle mass; however, which of the two phenomena is more critical is unclear. Therefore, we intended to examine the relationship between body composition and non-alcoholic fatty liver disease progression as indicated by fibrosis and the non-alcoholic fatty liver disease activity score. METHODS: This cross-sectional study comprised 149 patients (55 men; age, 20-76 years) treated for non-alcoholic fatty liver disease between December 2010 and January 2020. Body composition measurements, histological examinations of liver samples, and comprehensive blood chemistry tests were performed. The relationship between body composition and non-alcoholic fatty liver disease histology findings was analyzed using the logistic regression model. RESULTS: Fibrosis was significantly and inversely correlated with muscle mass and appendicular skeletal muscle mass and significantly and positively correlated with fat mass, fat mass/height squared, visceral fat area, and waist-hip ratio (P < 0.05). After adjustment for sex, blood chemistry measurements, and body composition indices, fibrosis remained associated with appendicular skeletal muscle mass, fat mass, fat mass/height squared, and visceral fat area (P < 0.05). Non-alcoholic fatty liver disease activity score ≥ 5 significantly correlated with fat mass and fat mass/height squared in a univariate but not multivariate analysis. CONCLUSIONS: Fibrosis in non-alcoholic fatty liver disease, an indicator of unfavorable long-term outcomes, is associated with more indices of fat mass than of those of muscle mass. Hence, fat mass should be controlled to prevent non-alcoholic fatty liver disease progression.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Idoso , Composição Corporal , Estudos Transversais , Fibrose , Humanos , Gordura Intra-Abdominal/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto Jovem
13.
Nat Commun ; 12(1): 2388, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888702

RESUMO

To unravel the pathogenesis of obesity and its complications, we investigate the interplay between circadian clocks and NF-κB pathway in human adipose tissue. The circadian clock function is impaired in omental fat from obese patients. ChIP-seq analyses reveal that the core clock activator, BMAL1 binds to several thousand target genes. NF-κB competes with BMAL1 for transcriptional control of some targets and overall, BMAL1 chromatin binding occurs in close proximity to NF-κB consensus motifs. Obesity relocalizes BMAL1 occupancy genome-wide in human omental fat, thereby altering the transcription of numerous target genes involved in metabolic inflammation and adipose tissue remodeling. Eventually, clock dysfunction appears at early stages of obesity in mice and is corrected, together with impaired metabolism, by NF-κB inhibition. Collectively, our results reveal a relationship between NF-κB and the molecular clock in adipose tissue, which may contribute to obesity-related complications.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Relógios Circadianos/imunologia , Gordura Intra-Abdominal/patologia , NF-kappa B/metabolismo , Obesidade/complicações , Adipócitos/imunologia , Adipócitos/metabolismo , Adiponectina/genética , Adulto , Animais , Biópsia , Estudos de Casos e Controles , Células Cultivadas , Sequenciamento de Cromatina por Imunoprecipitação , Relógios Circadianos/genética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/imunologia , Inflamação/patologia , Gordura Intra-Abdominal/imunologia , Masculino , Células-Tronco Mesenquimais , Camundongos Transgênicos , Pessoa de Meia-Idade , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/patologia , Omento/imunologia , Omento/patologia , Proteínas Circadianas Period/genética , Cultura Primária de Células , Transcrição Genética
14.
Clin Nutr ESPEN ; 42: 354-360, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33745605

RESUMO

BACKGROUND & AIMS: The impact of obesity, evaluated using body mass index (BMI), on mortality in patients with cirrhosis is controversial. The prognostic impact of visceral fat accumulation, which is recommended as an indicator of obesity-related mortality, is still unknown. This study aimed to clarify the impact of visceral fat accumulation on mortality in patients with cirrhosis. METHODS: A total of 335 cirrhotic patients without hepatocellular carcinoma were retrospectively evaluated. The impact of obesity, defined as a visceral fat area ≥100 cm2 at the umbilical level or BMI ≥25 kg/m2 on mortality, was evaluated using competing risk analysis. RESULTS: Of 355 patients, visceral fat accumulation was seen in 147 patients. During the observation period (1340 ± 980 days), 84 patients died, and 17 received liver transplantation. Visceral fat accumulation was not found to be associated with mortality (hazard ratio [HR] 1.423, P = 0.180) in any of the patients. After stratification of the patients, visceral fat accumulation was observed to be associated with a poor prognosis in patients with skeletal muscle depletion (HR 3.804, P = 0.003), but not in those without (HR 1.147, P = 0.660). On the other hand, obesity defined by BMI ≥25 kg/m2 was not found to be associated with mortality in patients with (HR 0.341, P = 0.390) or without skeletal muscle depletion (HR 1.227, P = 0.500). CONCLUSIONS: Visceral fat accumulation is a useful index for evaluating obesity and aggravates mortality in cirrhotic patients with skeletal muscle depletion, but not in those without.


Assuntos
Gordura Intra-Abdominal , Neoplasias Hepáticas , Humanos , Gordura Intra-Abdominal/patologia , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Prognóstico , Estudos Retrospectivos
15.
PLoS One ; 16(3): e0248028, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33684155

RESUMO

The increasing prevalence of obesity among the institutionalised elderly population and its severe consequences on health requires an early and accurate diagnosis that can be easily achieved in any clinical setting. This study aimed to determine new cut-off values for anthropometric and bioelectrical impedance measures that are superior to body mass index criteria for overweight and obesity status in a sample of Spanish institutionalised elderly population. A total of 211 institutionalised older adults (132 women, aged 84.3±7.3 years; 79 men, aged 81.5±7.3 years) were enrolled in the current cross-sectional study. Anthropometric and bioelectrical impedance measures included the body mass index, waist circumference, gluteal circumference, waist-hip ratio, sagittal-abdominal diameter, trunk fat, and visceral-fat ratio. In women, the waist circumference, gluteal circumference, sagittal-abdominal diameter, trunk fat, and visceral-fat index presented strongly significant specificity and sensitivity (area under the curve [AUC], p<0.0001) and elevated discriminative values (receiver operating characteristic [ROC] curves: 0.827 to 0.867) for overweight and obesity status. In men, the waist-hip ratio, waist circumference, gluteal circumference, sagittal-abdominal diameter, trunk fat, and visceral-fat ratio were strongly significant AUC (p<0.0001), with moderate-to-high values (ROC curves: 0.757-0.871). In conclusion, our findings suggest that gluteal circumference, waist circumference, and sagittal-abdominal diameter in women and trunk fat, visceral-fat ratio, and waist circumference in men may represent more suitable cut-off values superior to body mass index criteria for overweight and obesity in the Spanish institutionalised elderly population.


Assuntos
Índice de Massa Corporal , Impedância Elétrica , Obesidade Abdominal , Diâmetro Abdominal Sagital , Relação Cintura-Quadril , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Masculino , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/patologia , Espanha/epidemiologia
16.
PLoS One ; 16(3): e0248594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33725017

RESUMO

In translational obesity research, objective assessment of adipocyte sizes and numbers is essential to characterize histomorphological alterations linked to obesity, and to evaluate the efficacies of experimental medicinal or dietetic interventions. Design-based quantitative stereological techniques based on the analysis of 2D-histological sections provide unbiased estimates of relevant 3D-parameters of adipocyte morphology, but often involve complex and time-consuming tissue processing and analysis steps. Here we report the application of direct 3D light sheet fluorescence microscopy (LSFM) for effective and accurate analysis of adipocyte volumes and numbers in optically cleared adipose tissue samples from a porcine model of diet-induced obesity (DIO). Subcutaneous and visceral adipose tissue samples from DIO-minipigs and lean controls were systematically randomly sampled, optically cleared with 3DISCO (3-dimensional imaging of solvent cleared organs), stained with eosin, and subjected to LSFM for detection of adipocyte cell membrane autofluorescence. Individual adipocytes were unbiasedly sampled in digital 3D reconstructions of the adipose tissue samples, and their individual cell volumes were directly measured by automated digital image analysis. Adipocyte numbers and mean volumes obtained by LSFM analysis did not significantly differ from the corresponding values obtained by unbiased quantitative stereological analysis techniques performed on the same samples, thus proving the applicability of LSFM for efficient analysis of relevant morphological adipocyte parameters. The results of the present study demonstrate an adipose tissue depot specific plasticity of adipocyte growth responses to nutrient oversupply. This was characterized by an exclusively hypertrophic growth of visceral adipocytes, whereas adipocytes in subcutaneous fat tissue depots also displayed a marked (hyperplastic) increase in cell number. LSFM allows for accurate and efficient determination of relevant quantitative morphological adipocyte parameters. The applied stereological methods and LSFM protocols are described in detail and can serve as a guideline for unbiased quantitative morphological analyses of adipocytes in other studies and species.


Assuntos
Adipócitos/patologia , Gordura Intra-Abdominal/patologia , Obesidade/patologia , Gordura Subcutânea/patologia , Animais , Contagem de Células/métodos , Tamanho Celular , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Gordura Intra-Abdominal/citologia , Microscopia de Fluorescência , Obesidade/etiologia , Gordura Subcutânea/citologia , Suínos , Porco Miniatura
17.
Nutrients ; 13(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525454

RESUMO

(1) Background. Visceral adiposity index (VAI) has been recently identified as a new cardiometabolic risk marker reflecting abdominal fat distribution and dyslipidaemia. The aim of the present paper was to evaluate the relationship between VAI, daily energy intake and metabolic syndrome (MetS) in a cohort of obese Caucasian children and adolescents, aged 8 to 15 years. (2) Methods. Consecutive Italian children and adolescents with obesity, according to World Health Organization were enrolled. Anthropometric parameters and blood pressure were measured. Fasting blood samples have been analyzed for lipids, insulin and glucose levels. MetS was diagnosed using identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) or International Diabetes Federation (IDF) criteria according to age. Homeostatic model assessment index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), A body shape index (ABSI) and VAI were calculated. Multivariable logistic regression analyses with sex, age and each anthropometric parameter (body mass index (BMI) z-score, ABSI, waist-to-height ratio (WHR)) or VAI was performed to predict MetS. Receiver operation curve (ROC) analysis was used to define the optimal VAI cut-off to identify MetS. Multiple regression was performed to predict the BMI z-score and VAI from daily energy intake after adjusting for age and sex. (3) Results. Six hundred and thirty-seven (313 boys and 324 girls) children and adolescents with obesity with median age 11 (interquartile range 10-13) years were included in the analysis. MetS was diagnosed in 79 patients. VAI correlated with BMI, WHR, ABSI, HOMA-IR, QUICKI, systolic blood pressure, low- and high-density lipoprotein cholesterol, triglycerides and triglycerides-to-HDL ratio (p < 0.050). Optimal VAI cut-off (AUC) values to identify MetS were 1.775 (0.774), 1.685 (0.776) and 1.875 (0.797) in the whole population, boys and girls, respectively. Energy intake was positively associated with BMI z-score but no association was found with VAI. (4) Conclusion. VAI is a promising tool to identify MetS in children and adolescents with obesity and should be used in the management of abdominal obesity together with dietary assessment.


Assuntos
Adiposidade , Ingestão de Energia , Gordura Intra-Abdominal/patologia , Síndrome Metabólica/diagnóstico , Obesidade Abdominal/epidemiologia , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Modelos Logísticos , Masculino , Curva ROC
18.
Obesity (Silver Spring) ; 29(3): 595-600, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33528915

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is associated with low bone mineral density (BMD); however, it is not known whether early-stage NAFLD may be associated with BMD after accounting for BMI or visceral adipose tissue (VAT). METHODS: This was a cross-sectional study of 3,462 Framingham Heart Study participants who underwent computed tomographic measurement of liver fat, VAT volume, volumetric spine BMD, vertebral cross-sectional area (CSA), and vertebral compressive strength. This study excluded heavy alcohol consumers. Multivariable linear regression models were used to assess the association between NAFLD and volumetric BMD, CSA, and vertebral compressive strength after accounting for covariates, including BMI or VAT. RESULTS: A total of 2,253 participants (mean age, 51.2 [SD 10.7] years; 51.1% women) were included. In multivariable-adjusted models, positive associations between NAFLD and integral BMD, trabecular BMD, and vertebral compressive strength were observed. However, results were attenuated and no longer significant after additionally adjusting for BMI or VAT. NAFLD was observed to be weakly associated with a lower vertebral CSA in adjusted models. CONCLUSIONS: In a community-based cohort, the associations between NAFLD and BMD and vertebral strength were confounded by BMI and VAT. However, NAFLD was associated with a reduced vertebral CSA in adjusted models.


Assuntos
Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/epidemiologia , Osteoporose/epidemiologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/metabolismo , Adiposidade/fisiologia , Adulto , Índice de Massa Corporal , Densidade Óssea/fisiologia , Fatores de Confusão Epidemiológicos , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/metabolismo , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/metabolismo , Osteoporose/complicações , Osteoporose/diagnóstico , Osteoporose/metabolismo , Características de Residência , Coluna Vertebral , Tomografia Computadorizada por Raios X
19.
Eur J Endocrinol ; 184(4): 533-541, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33524007

RESUMO

Context: The endocrine and immunological properties of subcutaneous vs visceral adipose tissue (sWAT and vWAT, respectively) have turned a milestone in the study of metabolic diseases. The cytokine S100A4 is increased in obesity and has a role in adipose tissue dysfunction. However, the cellular source and its potential role in hepatic damage in obesity has not been elucidated. Objective: We aim to study the regulation of S100A4 in immune cells present in sWAT and vWAT, as well as its potential role as a circulating marker of hepatic inflammation and steatosis. Design: A cohort of 60 patients with obesity and distinct metabolic status was analyzed. CD11b+ myeloid cells and T cells were isolated from sWAT and vWAT by magnetic-activating cell sorting, and RNA was obtained. S100A4 gene expression was measured, and correlation analysis with clinical data was performed. Liver biopsies were obtained from 20 patients, and S100A4 circulating levels were measured to check the link with hepatic inflammation and steatosis. Results: S100A4 gene expression was strongly upregulated in sWAT- vs vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides, TNF-α gene expression and proliferation markers. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers. Conclusion: Our data suggest that sWAT-infiltrated CD11b+ cells could be a major source of S100A4 in obesity. Moreover, our correlations identify circulating S100A4 as a potential novel biomarker of hepatic damage and steatosis.


Assuntos
Tecido Adiposo Branco/patologia , Antígeno CD11b/análise , Fígado Gorduroso/sangue , Células Mieloides/química , Obesidade/complicações , Proteína A4 de Ligação a Cálcio da Família S100/análise , Tecido Adiposo Branco/química , Tecido Adiposo Branco/metabolismo , Adulto , Idoso , Animais , Biomarcadores/análise , Biomarcadores/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Feminino , Expressão Gênica , Humanos , Gordura Intra-Abdominal/química , Gordura Intra-Abdominal/patologia , Macrófagos/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Células RAW 264.7 , Proteína A4 de Ligação a Cálcio da Família S100/sangue , Proteína A4 de Ligação a Cálcio da Família S100/genética , Gordura Subcutânea/química , Gordura Subcutânea/patologia
20.
Sci Rep ; 11(1): 1831, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469087

RESUMO

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT's adipocytes showed a lower range of size expandability than VAT's adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT's larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT's larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT's larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.


Assuntos
Adipócitos/metabolismo , Aterosclerose/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Adipócitos/patologia , Adulto , Aterosclerose/patologia , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Fatores de Risco , Gordura Subcutânea/patologia
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