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1.
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
2.
Medicine (Baltimore) ; 100(34): e27043, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449489

RESUMO

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for cardiac mortality. Pericoronary adipose tissue (PCAT) attenuation, expressed by the fat attenuation index on coronary computed tomography angiography, reflects pericoronary inflammation. We aimed to investigate the association between PCAT attenuation and NAFLD.This is a single-center cohort study comprising of patients who underwent coronary computed tomography angiography for suspected stable coronary artery disease between January and December 2020. Patient characteristics and coronary computed tomography angiography findings were analyzed between patients with NAFLD (n = 78) and a propensity score-matched cohort of patients without NAFLD (n = 78). PCAT attenuation was assessed in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery.The mean PCAT attenuation in LAD and right coronary artery were significantly higher in patients with NAFLD than those without NAFLD. When patients were divided into 2 groups using the median LAD-PCAT attenuation of -72.5 HU, the high PCAT attenuation group had more males (82% vs 67%, P = .028) and NAFLD patients (63% vs 37%, P = .001) compared to the low PCAT attenuation group. No differences in age, body mass index, conventional cardiovascular risk factors, or the presence of high-risk plaque were observed between the 2 groups. In the multivariate logistic analysis, NAFLD was independently associated with high PCAT attenuation (odds ratio 2.912, 95% confidence interval 1.386 to 6.118, P = .005).NAFLD is associated with high PCAT attenuation on coronary computed tomography angiography. This finding suggests that pericoronary inflammation is involved in the increased cardiac mortality in NAFLD patients.


Assuntos
Tecido Adiposo/patologia , Doença da Artéria Coronariana/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Tecido Adiposo/diagnóstico por imagem , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Comorbidade , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Pericárdio , Fatores Sexuais
3.
Cardiovasc Diabetol ; 20(1): 165, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384426

RESUMO

BACKGROUND: COVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission. METHODS: Eighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined. RESULTS: Of the enrolled patients (median age 66 years [IQR: 59-74]), 73% male, median body mass index (BMI) 27 kg/m2 [IQR: 24-31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2, p < 0.0001) and ICU-R (respectively OR = 3.27, p = 0.01; OR = 4.86, p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p < 0.0001). CONCLUSIONS: Cardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission, a fortiori associated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.


Assuntos
Tecido Adiposo/patologia , COVID-19/sangue , Diabetes Mellitus Tipo 2/complicações , Interleucina-6/sangue , Miocárdio/patologia , Tecido Adiposo/diagnóstico por imagem , Idoso , COVID-19/complicações , COVID-19/diagnóstico por imagem , COVID-19/mortalidade , Feminino , Coração/diagnóstico por imagem , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Prognóstico , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
4.
Molecules ; 26(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203841

RESUMO

Screening for systemic amyloidosis is typically carried out with abdominal fat aspirates with varying reported sensitivities. Fat aspirates are preferred for use in primary screening instead of organ biopsies as they are less invasive and thereby minimize the potential risk of complications. At Odense Amyloidosis Center, we performed a prospective study on whether the combined use of fat aspirate and tru-cut skin biopsy could increase the diagnostic sensitivity. Both fat aspirates and skin biopsies were screened with Congo Red staining, and positive biopsies were subsequently subtyped using immunoelectron microscopy and mass spectrometry. Seventy-six patients were included. In total, 24 patients had systemic amyloidosis (11 AL, 12 wtATTR, 1 AA), and 6 patients had localized amyloidosis. Combined fat aspirate and skin biopsy were Congo Red-positive in 15 patients (overall sensitivity (OS) 62.5%). Fat aspirates were positive in 14 patients (OS 58.3%), and the skin biopsy was positive in 5 patients (OS 20.8%). In only one patient did the skin biopsy add extra diagnostic information. The sensitivity differed between AL and ATTR amyloidosis-81.8% and 41.7%, respectively. Using skin biopsy as the only screening method is not recommended.


Assuntos
Proteínas Amiloidogênicas/análise , Amiloidose/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Tecido Adiposo/patologia , Adulto , Idoso , Amiloide/análise , Amiloidose/metabolismo , Biópsia/efeitos adversos , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/metabolismo , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Pele/patologia , Coloração e Rotulagem/métodos , Gordura Subcutânea/patologia
5.
Aging (Albany NY) ; 13(13): 17489-17498, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232916

RESUMO

BACKGROUND AND PURPOSE: Obesity is becoming a major global health issue and is mainly induced by the accumulation of adipose tissues mediated by adipogenesis, which is reported to be regulated by peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer-binding protein α (C/EBPα). Trichostatin A (TSA) is a novel histone deacetylase inhibitor (HDACI) that was recently reported to exert multiple pharmacological functions. The present study will investigate the inhibitory effect of TSA on adipogenesis, as well as the underlying mechanism. METHODS: The adipogenesis of 3T3-L1 cells was induced by stimulation with a differentiation cocktail (DMI) medium for 8 days. MTT assay was used to measure the cell viability and Oil Red O staining was used to evaluate the adipogenesis of 3T3-L1 cells. The total level of triglyceride and released glycerol were detected to evaluate the lipolysis during 3T3-L1 adipogenesis. The expression levels of Leptin, fatty acid-binding protein 4 (FABP4), and sterol regulatory element-binding protein (SREBP1C) were determined by qRT-PCR. qRT-PCR assay was utilized to detect the expression levels of PPARγ and C/EBPα in 3T3-L1 cells. A high-fat diet (HFD) was used to construct an obese mice model, followed by the treatment with TSA. HE staining was conducted to evaluate the pathological state of adipose tissues. Body weights and the weights of adipose tissues were recorded to evaluate the anti-obesity property of TSA. RESULTS: Firstly, the promoted lipid accumulation induced by DMI incubation was significantly reversed by the treatment with TSA in a dose-dependent manner. The elevated expression levels of Leptin, FABP4, SREBP1C, PPARγ, and C/EBPα induced by the stimulation with DMI incubation were dramatically inhibited by the introduction of TSA, accompanied by the upregulation of phosphorylated AMP-activated protein kinase (p-AMPK). Secondly, the inhibitory effect of TSA against the expression level of PPARγ and lipid accumulation was greatly abolished by an AMPK inhibitor. Lastly, the increased body weights and visceral adipocyte tissue weight, as well as the enlarged size of adipocytes induced by HFD were pronouncedly reversed by the administration of TSA. CONCLUSION: TSA inhibited adipogenesis in 3T3-L1 preadipocytes by activating the AMPK pathway.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Células 3T3-L1 , Tecido Adiposo/patologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Proteínas de Ligação a Ácido Graxo/genética , Glicerol/metabolismo , Leptina/metabolismo , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Obesos , Obesidade/genética , Triglicerídeos/metabolismo
6.
Int J Mol Sci ; 22(14)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34299048

RESUMO

Adipose tissue (AT) is an endocrine organ involved in the management of energy metabolism via secretion of adipokines, hormones, and recently described secretory microvesicles, i.e., exosomes. Exosomes are rich in possible biologically active factors such as proteins, lipids, and RNA. The secretory function of adipose tissue is affected by pathological processes. One of the most important of these is obesity, which triggers adipose tissue inflammation and adversely affects the release of beneficial adipokines. Both processes may lead to further AT dysfunction, contributing to changes in whole-body metabolism and, subsequently, to insulin resistance. According to recent data, changes within the production, release, and content of exosomes produced by AT may be essential to understand the role of adipose tissue in the development of metabolic disorders. In this review, we summarize actual knowledge about the possible role of AT-derived exosomes in the development of insulin resistance, highlighting methodological challenges and potential gains resulting from exosome studies.


Assuntos
Tecido Adiposo/patologia , Exossomos/patologia , Intolerância à Glucose/patologia , Resistência à Insulina , Animais , Intolerância à Glucose/etiologia , Humanos
7.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298949

RESUMO

Sodium glucose cotransporter-2 (SGLT2) inhibitors inhibit the development of diabetic nephropathy (DN). We determined whether changes in perirenal fat (PRAT) by a SGLT2 inhibitor ipragliflozin (Ipra) contribute to the suppression of DN development. High-fat diet (HFD)-fed mice were used as a DN model and were treated with or without Ipra for 6 weeks. Ipra treatment reduced urinary albumin excretion (UAE) and glomerular hypertrophy in HFD-fed mice. In the PRAT of Ipra-treated mice, adipocyte size was increased, and inflammation, fibrosis, and adipocyte death were suppressed. In conditioned medium made from PRAT (PRAT-CM) of Ipra-treated mice, the concentration of leptin was significantly lower than PRAT-CM of mice without Ipra treatment. Serum leptin concentration in renal vein positively correlated with UAE. PRAT-CM from HFD-fed mice showed greater cell proliferation signaling in mouse glomerular endothelial cells (GECs) than PRAT-CM from standard diet-fed mice via p38MAPK and leptin-dependent pathways, whose effects were significantly attenuated in PRAT-CM from Ipra-treated mice. These findings suggest that Ipra-induced PRAT expansion may play an important role in the improvement of DN in HFD-fed mice. In vitro experiments suggest that reduced PRAT-derived leptin by Ipra could inhibit GECs proliferation, possibly contributing to the suppression of DN development.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Glucosídeos/metabolismo , Glomérulos Renais/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Tiofenos/metabolismo , Tecido Adiposo/patologia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Glomérulos Renais/patologia , Masculino , Camundongos
8.
FEBS Lett ; 595(16): 2099-2112, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34165806

RESUMO

Periostin (POSTN) is a type of matricellular protein, but its functions in adipose fibrosis remain unclear. Here, we found that POSTN expression is significantly increased in mouse adipose tissue after treatment with lipopolysaccharide (LPS) or a high-fat diet (HFD) and that adipose progenitor cells are the main source of POSTN. In our mouse model of fibrosis, POSTN deletion protected mice from adipose fibrosis, probably through reducing the accumulation of macrophages and promoting adipocyte differentiation of progenitor cells. Taken together, our study demonstrates that POSTN deficiency attenuates adipose tissue fibrosis and improves insulin resistance, providing new insights into the diagnosis and treatment of type II diabetes by targeting adipose tissue fibrosis.


Assuntos
Tecido Adiposo/patologia , Moléculas de Adesão Celular/deficiência , Lipopolissacarídeos/farmacologia , Obesidade/patologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Moléculas de Adesão Celular/genética , Dieta Hiperlipídica/efeitos adversos , Fibrose , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL
9.
Aging (Albany NY) ; 13(11): 14806-14815, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088886

RESUMO

Myocardial fibrosis is considered a key pathological process in the development of cardiovascular diseases. In epicardial obesity (EO), the main cause of fibrosis development is lipotoxic myocardial damage. It is important to detect myocardial fibrosis at an early stage, using non-invasive diagnostic methods. According to the results of echocardiography (ECG), 110 men with general obesity were divided into the following two groups: Group I with epicardial fat thickness (tEAT) ≥ 7 mm (n = 70) and Group II with tEAT < 7 mm (n = 40) without diastolic dysfunction. The levels of metabolic factors, pro-inflammatory cytokines, adipokines, and free fatty acids (FFA), profibrotic markers were determined in both groups. In Group I, the level of interleukin (IL)-6, C-reactive protein, and tumor necrosis factor (TNF)-α increased and that of leptin and adiponectin decreased compared with those in Group II. There was an increase in the level of all studied profibrotic factors in Group I. The level of TNF-α and IL-6 showed a positive correlation with the level of leptin and FFA and a negative correlation with the level of adiponectin. We also observed a relationship between the level of collagen, transforming growth factor (TGF)-ß, and metalloproteinase (MMP)-3 and EO. Our results showed that confirmed EO correlates with not only disadipocytosis and increased levels of pro-inflammatory cytokines, but also increased levels of profibrotic factors. This suggests that the studied markers of fibrosis may be used to determine preclinical cardiac fibrosis with lipotoxic myocardial damage in patients with EO.


Assuntos
Lipídeos/efeitos adversos , Miocárdio/patologia , Obesidade/patologia , Pericárdio/patologia , Adipocinas/metabolismo , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Biomarcadores/metabolismo , Fibrose , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Neurotransmissores , Pericárdio/diagnóstico por imagem , Fatores de Risco , Estatísticas não Paramétricas
10.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067001

RESUMO

Investigations into the mechanisms regulating obesity are frantic and novel translational approaches are needed. The raccoon dog (Nyctereutes procyonoides) is a canid species representing a promising model to study metabolic regulation in a species undergoing cycles of seasonal obesity and fasting. To understand the molecular mechanisms of metabolic regulation in seasonal adaptation, we analyzed key central nervous system and peripheral signals regulating food intake and metabolism from raccoon dogs after autumnal fattening and winter fasting. Expressions of neuropeptide Y (NPY), orexin-2 receptor (OX2R), pro-opiomelanocortin (POMC) and leptin receptor (ObRb) were analyzed as examples of orexigenic and anorexigenic signals using qRT-PCR from raccoon dog hypothalamus samples. Plasma metabolic profiles were measured with 1H NMR-spectroscopy and LC-MS. Circulating hormones and cytokines were determined with canine specific antibody assays. Surprisingly, NPY and POMC were not affected by the winter fasting nor autumn fattening and the metabolic profiles showed a remarkable equilibrium, indicating conserved homeostasis. However, OX2R and ObRb expression changes suggested seasonal regulation. Circulating cytokine levels were not increased, demonstrating that the autumn fattening did not induce subacute inflammation. Thus, the raccoon dog developed seasonal regulatory mechanisms to accommodate the autumnal fattening and prolonged fasting making the species unique in coping with the extreme environmental challenges.


Assuntos
Adiposidade , Jejum/metabolismo , Metaboloma , Cães Guaxinins/metabolismo , Estações do Ano , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal , Análise Discriminante , Feminino , Hormônios/sangue , Hipotálamo/metabolismo , Inflamação/patologia , Análise dos Mínimos Quadrados , Limite de Detecção , Análise Multivariada , Peptídeos/genética , Peptídeos/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Cães Guaxinins/sangue , Receptores de Peptídeos/metabolismo
11.
Front Endocrinol (Lausanne) ; 12: 652639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995281

RESUMO

Obesity has been recognized as an independent risk factor for critical illness and major severity in subjects with coronavirus disease 2019 (COVID-19). The role of fat distribution, particularly visceral fat (often linked to metabolic abnormalities), is still unclear. The adipose tissue represents a direct source of cytokines responsible for the pathological modifications occurring within adipose tissue in obese subjects. Adipokines are a crucial connection between metabolism and immune system: their dysregulation in obesity contributes to chronic low-grade systemic inflammation and metabolic comorbidities. Therefore the increased amount of visceral fat can lead to a proinflammatory phenotypic shift. This review analyzes the interrelation between obesity and COVID-19 severity, as well as the cellular key players and molecular mechanisms implicated in adipose inflammation, investigating if adipose tissue can constitute a reservoir for viral spread, and contribute to immune activation and cytokines storm. Targeting the underlying molecular mechanisms might have therapeutic potential in the management of obesity-related complications in COVID-19 patients.


Assuntos
COVID-19/complicações , Obesidade/complicações , Gordura Abdominal/patologia , Tecido Adiposo/patologia , COVID-19/fisiopatologia , Humanos , Inflamação/etiologia , Obesidade/fisiopatologia
12.
Am J Physiol Endocrinol Metab ; 321(1): E169-E175, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34056922

RESUMO

Adipose is a key tissue regulating energy homeostasis. In states of obesity, caloric intake exceeds energy expenditure, thereby accelerating lipid accumulation with ongoing extracellular matrix (ECM) remodeling. Excess deposition of lipids and expansion of adipocytes potentially decrease ECM flexibility with local hypoxia and inflammation. Hypoxia and chronic low-grade inflammation accelerate the development of adipose tissue fibrosis and related metabolic dysfunctions. Recent research investigated that some cytokines and proteins are functional in regulating energy homeostasis, meanwhile, are potential targets to fight against adipose tissue fibrosis and insulin resistance. In this review, we focused on the regulatory mechanisms and mediators in remodeling of adipose tissue fibrosis, along with their relevance to clinical manifestations.


Assuntos
Tecido Adiposo/patologia , Metabolismo Energético/fisiologia , Adipócitos/fisiologia , Tecido Adiposo/fisiopatologia , Animais , Glicemia/metabolismo , Citocinas , Matriz Extracelular/fisiologia , Fibrose , Homeostase/fisiologia , Humanos , Inflamação , Metabolismo dos Lipídeos/fisiologia , Doenças Metabólicas/fisiopatologia , Mitocôndrias/fisiologia , Obesidade/fisiopatologia
13.
Traffic Inj Prev ; 22(5): 407-412, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037475

RESUMO

OBJECTIVE: The objective of this study was to improve head-neck kinematic predictions of a contemporary finite element (FE) head-neck model, assessed in rear impact scenarios (3-10 g), by including an accurate representation of the skin, adipose tissue, and passive muscle mechanical properties. The soft tissues of the neck have a substantial contribution to kinematic response, with the contribution being inversely proportional to the impact severity. Thus accurate representation of these passive tissues is critical for the assessment of kinematic response and the potential for crash induced injuries. Contemporary Human Body Models (HBMs) often incorporate overly stiff mechanical properties of passive tissues for numerical stability, which can affect the predicted kinematic response of the head and neck. METHODS: Soft tissue material properties including non-linearity, compression-tension asymmetry, and viscoelasticity were implemented in constitutive models for the skin, adipose, and passive muscle tissues, based on experimental data in the literature. A quasi-linear viscoelastic formulation was proposed for the skin, while a phenomenological hyper-viscoelastic model was used for the passive muscle and adipose tissues. A head-neck model extracted from a contemporary FE HBM was updated to include the new tissue models and assessed using head rotation angle for rear impact scenarios (3 g, 7 g, and 10 g peak accelerations), and compared to postmortem human surrogate (PMHS) data for 7 g impacts. RESULTS: The head rotation angle increased with the new material models for all three rear impact cases: (3 g: +43%, 7 g: +52%, 10 g: +71%), relative to the original model. The increase in head rotation was primarily attributed to the improved skin model, with the passive muscle being a secondary contributor to the increase in response. A 52% increase in head rotation for the 7 g impact improved the model response with respect to PMHS data, placing it closer to the experimental average, compared to the original model. CONCLUSIONS: The improved skin, adipose tissue, and passive muscle material model properties, based on published experimental data, increased the neck compliance in rear impact, with improved correspondence to published PMHS test data for medium severity impacts. Future studies will investigate the coupled effect of passive and active muscle tissue for low severity impacts.


Assuntos
Acidentes de Trânsito , Tecido Adiposo/patologia , Músculos do Pescoço/patologia , Traumatismos em Chicotada/patologia , Aceleração , Fenômenos Biomecânicos , Cadáver , Análise de Elementos Finitos , Cabeça/patologia , Humanos , Pescoço/patologia
15.
Clin Ter ; 172(3): 190-192, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33956034

RESUMO

Abstract: Madelung's disease is a rare syndrome characterized by the pre-sence of multiple masses of unencapsulated adipose tissue, symme-trically distributed throughout different regions. It predominantly affects middle-aged men of Mediterranean origin with a history of alcoholism. The pathogenesis is still unknown. Diagnosis is essentially established through clinical history and physical examination. We report two cases for their unusual presentation and to emphasize the importance of early diagnosis.


Assuntos
Tecido Adiposo/patologia , Lipomatose Simétrica Múltipla/diagnóstico , Alcoolismo/complicações , Feminino , Humanos , Lipomatose Simétrica Múltipla/patologia , Masculino , Pessoa de Meia-Idade , Síndrome
16.
Oxid Med Cell Longev ; 2021: 6663948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953836

RESUMO

Objective: To explore the association between EAT volume and plaque precise composition and high risk plaque detected by coronary computed tomography angiography (CCTA). Methods: 101 patients with suspected coronary artery disease (CAD) underwent CCTA examination from March to July 2019 were enrolled, including 70 cases acute coronary syndrome (ACS) and 31 cases stable angina pectoris (SAP). Based on CCTA image, atherosclerotic plaque precise compositions were analyzed using dedicated quantitative software. High risk plaque was defined as plaque with more than 2 high risk features (spotty calcium, positive remolding, low attenuation plaque, napkin-ring sign) on CCTA image. The association between EAT volume and plaque composition was assessed as well as the different of correlation between ACS and SAP was analyzed. Multivariable logistic regression analysis was used to explore whether EAT volume was independent risk factors of high risk plaque (HRP). Results: EAT volume in the ACS group was significantly higher than that of the SAP group (143.7 ± 49.8 cm3 vs. 123.3 ± 39.2 cm3, P = 0.046). EAT volume demonstrated a significant positive correlation with total plaque burden (r = 0.298, P = 0.003), noncalcified plaque burden (r = 0.245, P = 0.013), lipid plaque burden (r = 0.250, P = 0.012), and homocysteine (r = 0.413, P ≤ 0.001). In ACS, EAT volume was positively correlated with total plaque burden (r = 0.309, P = 0.009), noncalcified plaque burden (r = 0.242, P = 0.044), and lipid plaque burden (r = 0.240, P = 0.045); however, no correlation was observed in SAP. Patients with HRP have larger EAT volume than those without HRP (169 ± 6.2 cm3 vs. 130.6 ± 5.3 cm3, P = 0.002). After adjustment by traditional risk factors and coronary artery calcium score (CACS), EAT volume was an independent risk predictor of presence of HRP (OR: 1.018 (95% CI: 1.006-1.030), P = 0.004). Conclusions: With the increasing EAT volume, more dangerous plaque composition burdens increase significantly. EAT volume is a risk predictor of HRP independent of convention cardiovascular risk factors and CACS, which supports the potential impact of EAT on progression of coronary atherosclerotic plaque.


Assuntos
Síndrome Coronariana Aguda/fisiopatologia , Tecido Adiposo/patologia , Placa Aterosclerótica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
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
18.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33836591

RESUMO

White adipose tissue (WAT) is a key regulator of systemic energy metabolism, and impaired WAT plasticity characterized by enlargement of preexisting adipocytes associates with WAT dysfunction, obesity, and metabolic complications. However, the mechanisms that retain proper adipose tissue plasticity required for metabolic fitness are unclear. Here, we comprehensively showed that adipocyte-specific DNA methylation, manifested in enhancers and CTCF sites, directs distal enhancer-mediated transcriptomic features required to conserve metabolic functions of white adipocytes. Particularly, genetic ablation of adipocyte Dnmt1, the major methylation writer, led to increased adiposity characterized by increased adipocyte hypertrophy along with reduced expansion of adipocyte precursors (APs). These effects of Dnmt1 deficiency provoked systemic hyperlipidemia and impaired energy metabolism both in lean and obese mice. Mechanistically, Dnmt1 deficiency abrogated mitochondrial bioenergetics by inhibiting mitochondrial fission and promoted aberrant lipid metabolism in adipocytes, rendering adipocyte hypertrophy and WAT dysfunction. Dnmt1-dependent DNA methylation prevented aberrant CTCF binding and, in turn, sustained the proper chromosome architecture to permit interactions between enhancer and dynamin-1-like protein gene Dnm1l (Drp1) in adipocytes. Also, adipose DNMT1 expression inversely correlated with adiposity and markers of metabolic health but positively correlated with AP-specific markers in obese human subjects. Thus, these findings support strategies utilizing Dnmt1 action on mitochondrial bioenergetics in adipocytes to combat obesity and related metabolic pathology.


Assuntos
Adipócitos/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Epigênese Genética , Dinâmica Mitocondrial , Adipócitos/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adiposidade , Animais , Fator de Ligação a CCCTC/metabolismo , Estruturas Cromossômicas , DNA (Citosina-5-)-Metiltransferase 1/deficiência , DNA (Citosina-5-)-Metiltransferase 1/genética , Metilação de DNA , Dinaminas/genética , Dinaminas/metabolismo , Metabolismo Energético , Elementos Facilitadores Genéticos , Perfilação da Expressão Gênica , Metabolismo dos Lipídeos , Camundongos , Mitocôndrias/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Regiões Promotoras Genéticas , Ligação Proteica
19.
Nat Rev Endocrinol ; 17(6): 350-363, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33927368

RESUMO

This Review focuses on the mechanistic evidence for a link between obesity, dysregulated cellular metabolism and breast cancer. Strong evidence now links obesity with the development of 13 different types of cancer, including oestrogen receptor-positive breast cancer in postmenopausal women. A number of local and systemic changes are hypothesized to support this relationship, including increased circulating levels of insulin and glucose as well as adipose tissue-derived oestrogens, adipokines and inflammatory mediators. Metabolic pathways of energy production and utilization are dysregulated in tumour cells and this dysregulation is a newly accepted hallmark of cancer. Dysregulated metabolism is also hypothesized to be a feature of non-neoplastic cells in the tumour microenvironment. Obesity-associated factors regulate metabolic pathways in both breast cancer cells and cells in the breast microenvironment, which provides a molecular link between obesity and breast cancer. Consequently, interventions that target these pathways might provide a benefit in postmenopausal women and individuals with obesity, a population at high risk of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Redes e Vias Metabólicas/fisiologia , Obesidade/metabolismo , Microambiente Tumoral/fisiologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Obesidade/epidemiologia , Obesidade/patologia , Fatores de Risco
20.
JAMA Netw Open ; 4(4): e218524, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33929520

RESUMO

Importance: Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. Objective: To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. Design, Setting, and Participants: This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Exposures: Childhood FM and weight at ages 10 and 13 years. Main Outcomes and Measures: Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. Results: This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR, 1.15; 95% CI, 1.13-1.17) and 10% (HR, 1.10; 95% CI, 1.08-1.11), respectively. Among children aged 13 years, increases in FM and weight (per kilogram) were associated with increased T2D risks at age 50 years of 10% (HR, 1.10; 95% CI, 1.09-1.10) and 6% (HR, 1.06; 95% CI, 1.05-1.07) for boys, respectively, and of 10% (HR, 1.10; 95% CI, 1.10-1.11) and 7% (HR, 1.07; 95% CI, 1.06-1.08), respectively, for girls. Conclusions and Relevance: This cohort study found that a 1-kg increase in childhood FM was more strongly associated with increased adult T2D risk than a 1-kg increase in weight, independent of childhood height. Information on FM, rather than weight-based measures, focuses on a modifiable component of weight that may be associated with adult T2D risk. These findings support the assessment of childhood FM in adiposity surveillance initiatives in an effort to reduce long-term T2D risk.


Assuntos
Tecido Adiposo/patologia , Composição Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Adulto , Estatura , Criança , Dinamarca/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais
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