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1.
Internist (Berl) ; 61(10): 1063-1075, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32930809

RESUMO

Lipodystrophy (LD) syndromes are a group of rare and heterogeneous diseases characterized by a congenital deficiency or acquired loss of adipose tissue. Due to the resulting disorder of metabolism, sometimes severe sequelae can develop, such as hypertriglyceridemia, marked insulin resistance and early manifestation of type 2 diabetes, recurrent pancreatitis, fatty liver disease and liver fibrosis. Lipodystrophies are clinically recognizable due to the complete lack of subcutaneous adipose tissue or a conspicuous pattern of the distribution of body fat. Acanthosis nigricans in slimly built persons, a high fasting triglyceride level and elevated concentrations of liver enzymes as well as a positive history of pancreatitis can be indications of LD.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Lipoatrófica , Resistência à Insulina , Lipodistrofia , Tecido Adiposo/patologia , Diabetes Mellitus Tipo 2 , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/etiologia , Lipodistrofia/metabolismo , Lipodistrofia/terapia , Doenças Raras
2.
J Transl Med ; 18(1): 299, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746930

RESUMO

BACKGROUND: Obesity and steatosis are associated with COVID-19 severe pneumonia. Elevated levels of pro-inflammatory cytokines and reduced immune response are typical of these patients. In particular, adipose tissue is the organ playing the crucial role. So, it is necessary to evaluate fat mass and not simpler body mass index (BMI), because BMI leaves a portion of the obese population unrecognized. The aim is to evaluate the relationship between Percentage of Fat Mass (FM%) and immune-inflammatory response, after 10 days in Intensive Care Unit (ICU). METHODS: Prospective observational study of 22 adult patients, affected by COVID-19 pneumonia and admitted to the ICU and classified in two sets: (10) lean and (12) obese, according to FM% and age (De Lorenzo classification). Patients were analyzed at admission in ICU and at 10th day. RESULTS: Obese have steatosis, impaired hepatic function, compromise immune response and higher inflammation. In addition, they have a reduced prognostic nutritional index (PNI), nutritional survival index for ICU patients. CONCLUSION: This is the first study evaluating FM% in COVID-19 patient. We underlined obese characteristic with likely poorly prognosis and an important misclassification of obesity. A not negligible number of patients with normal BMI could actually have an excess of adipose tissue and therefore have an unfavorable outcome such as an obese. Is fundamental personalized patients nutrition basing on disease phases.


Assuntos
Adiposidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Cuidados Críticos/métodos , Estado Nutricional , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Adulto , Betacoronavirus , Índice de Massa Corporal , Feminino , Humanos , Inflamação , Unidades de Terapia Intensiva , Masculino , Avaliação Nutricional , Obesidade/complicações , Pandemias , Prognóstico , Estudos Prospectivos
3.
Life Sci ; 258: 118204, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32763296

RESUMO

AIMS: Liver kinase B1 (LKB1) is a serine/threonine kinase. Although many biological functions of LKB1 have been identified, the role of hypothalamic LKB1 in the regulation of central energy metabolism and susceptibility to obesity is unknown. Therefore, we constructed POMC neuron-specific LKB1 knockout mice (PomcLkb1 KO) and studied it at the physiological, morphological, and molecular biology levels. MAIN METHODS: Eight-week-old male PomcLkb1 KO mice and their littermates were fed a standard chow fat diet (CFD) or a high-fat diet (HFD) for 3 months. Body weight and food intake were monitored. Dual-energy X-ray absorptiometry was used to measure the fat mass and lean mass. Glucose and insulin tolerance tests and serum biochemical markers were evaluated in the experimental mice. In addition, the levels of peripheral lipogenesis genes and central energy metabolism were measured. KEY FINDINGS: PomcLkb1 KO mice did not exhibit impairments under normal physiological conditions. After HFD intervention, the metabolic phenotype of the PomcLkb1 KO mice changed, manifesting as increased food intake and an enhanced obesity phenotype. More seriously, PomcLkb1 KO mice showed increased leptin resistance, worsened hypothalamic inflammation and reduced POMC neuronal expression. SIGNIFICANCE: We provide evidence that LKB1 in POMC neurons plays a significant role in regulating energy homeostasis. LKB1 in POMC neurons emerges as a target for therapeutic intervention against HFD-induced obesity and metabolic diseases.


Assuntos
Deleção de Genes , Neurônios/enzimologia , Obesidade/enzimologia , Pró-Opiomelanocortina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Tecido Adiposo/patologia , Animais , Dieta Hiperlipídica , Epididimo/patologia , Comportamento Alimentar , Regulação da Expressão Gênica , Glucose/metabolismo , Hipotálamo/patologia , Inflamação/patologia , Leptina/metabolismo , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Obesidade/sangue , Obesidade/patologia , Pró-Opiomelanocortina/genética , Ganho de Peso
4.
PLoS One ; 15(8): e0237974, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841271

RESUMO

BACKGROUND: Cardiometabolic disorders are frequently observed among those who have obesity as measured by body mass index (BMI). However, there is limited data available on the cardiometabolic profile of those who are non-obese by BMI but with a high body fat percentage (BFP), a phenotype frequently observed in the Indian population. We examined the prevalence of individuals with normal weight obesity (NWO) and the cardiometabolic profile of NWO individuals at high risk for type 2 diabetes(T2D) in a south Asian population. MATERIAL AND METHODS: In the Kerala Diabetes Prevention Program, individuals aged between 30 to 60 years were screened using the Indian Diabetes Risk Score(IDRS) in 60 rural communities in the Indian state of Kerala. We used data from the baseline survey of this trial for this analysis which included 1147 eligible high diabetes risk individuals(IDRS >60). NWO was defined as BMI within the normal range and a high BFP (as per Asia-pacific ethnicity based cut-off); Non-obese (NO) as normal BMI and BFP and overtly obese (OB) as BMI ≥25 kg/m2 irrespective of the BFP. Data on demographic, clinical and biochemical characteristics were collected using standardized questionnaires and protocols. Body fat percentage was assessed using TANITA body composition analyser (model SC330), based on bioelectrical impedance. RESULTS: The mean age of participants was 47.3 ± 7.5 years and 46% were women. The proportion with NWO was 32% (n = 364; 95% CI: 29.1 to 34.5%), NO was 17% (n = 200) and OB was 51% (n = 583). Among those with NWO, 19.7% had T2D, compared to 18.7% of those who were OB (p value = 0.45) and 8% with NO (p value = 0.003). Among those with NWO, mean systolic and diastolic blood pressure were 129 ± 20; 78 ± 12 mmHg, compared to 127 ± 17; 78±11 mmHg among those with OB (p value = 0.12;0.94) and 120 ± 16; 71±10 mmHg among with NO (p value<0.001; 0.001), respectively. A similar pattern of association was observed for LDL cholesterol and triglycerides. After adjusting for other risk factors, the odds of having diabetes (OR:2.72[95% CI:1.46-5.08]) and dyslipidemia (2.37[1.55-3.64]) was significantly more in individuals with NWO as compared to non-obese individuals. CONCLUSIONS: Almost one-third of this South Asian population, at high risk for T2D, had normal weight obesity. The significantly higher cardiometabolic risk associated with increased adiposity even in lower BMI individuals has important implications for recognition in clinical practice.


Assuntos
Tecido Adiposo/patologia , Peso Corporal , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/prevenção & controle , Miocárdio/metabolismo , Obesidade/epidemiologia , Obesidade/metabolismo , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Fenótipo , Prevalência , Fatores de Risco
5.
Medicine (Baltimore) ; 99(27): e21139, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629749

RESUMO

INTRODUCTION: Most symptomatic large-to-massive rotator cuff tears (RCTs) should be operated, but the surgical reparability depended on the degree of rotator cuff muscle atrophy or fatty infiltration. The orthopedic surgeons will decide whether the teared stump is reparable during the surgery, but preoperative evaluation can be done by some assessment tools. Magnetic resonance imaging (MRI) was used in recent studies to predict the reparability of large-to-massive RCTs, but the clinical availability was not as good as ultrasound. We hypothesize that the ultrasound elastography can predict the reparability of large-to-massive RCTs. METHODS: This is a prospective observational study and participants with large-to-massive RCTs who are going to have surgeries will be included. Out investigators will evaluate the shoulder passive range of motion (ROM) and strength of all participants. Participants' degree of shoulder pain and activities of daily living (ADLs) will be assessed by American Shoulder and Elbow Surgeons (ASES) score. The ultrasound elastography will be used to evaluate the tissue quality of supraspinatus muscle and infraspinatus muscle. To test the reliability of the ultrasound elastography, two physicians will perform the ultrasound elastography independently and twenty participants will be selected for the reliability test. Besides, MRI will be used to evaluate the size of tear, the degree of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, the orthopedic surgeons will perform surgeries and decide whether the teared stump can be completely repaired intraoperatively. The primary analysis is the predictive validity of ultrasound elastography for the reparability of large-to-massive RCTs. Before the predictive validity of ultrasound elastography is measured, our investigators will assess the reliability of ultrasound elastography when administered to cases with large-to-massive RCTs, and we will check the correlations between the findings of ultrasound elastography and MRI. DISCUSSION: The outcome will provide the evidence of ultrasound elastography for preoperative evaluation of large-to-massive RCTs. The relationships between the findings of ultrasound elastography and MRI will also be examined for further analysis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03682679. Date of Registration: 25 September 2018, https://clinicaltrials.gov/ct2/show/NCT03682679?cond=rotator+cuff&cntry=TW&draw=2&rank=1.


Assuntos
Lesões do Manguito Rotador/diagnóstico por imagem , Ruptura/cirurgia , Ombro/fisiopatologia , Atividades Cotidianas , Tecido Adiposo/patologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Atrofia Muscular/patologia , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologia , Reprodutibilidade dos Testes , Manguito Rotador/patologia , Lesões do Manguito Rotador/patologia
6.
Nat Commun ; 11(1): 3755, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709874

RESUMO

Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders.


Assuntos
Disbiose/imunologia , Inflamação/patologia , Intestinos/patologia , Células T Invariáveis Associadas à Mucosa/patologia , Obesidade/metabolismo , Tecido Adiposo/patologia , Animais , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica , Disbiose/complicações , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Íleo/patologia , Inflamação/complicações , Mucosa Intestinal/patologia , Intestinos/diagnóstico por imagem , Ligantes , Contagem de Linfócitos , Macrófagos/metabolismo , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/diagnóstico por imagem , Fenótipo , Pterinas/farmacologia , Receptores de Antígenos de Linfócitos T/metabolismo
7.
Br J Radiol ; 93(1114): 20200540, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706985

RESUMO

OBJECTIVE: This study sought to investigate the association between volume and attenuation of epicardial fat and presence of obstructive coronary artery disease (CAD) and high-risk plaque features (HRPF) on CT angiography (CTA) in patients with atypical chest pain and whether the association, if any, is independent of conventional cardiovascular risk factors and coronary artery calcium score (CACS). METHODS: Patients referred for coronary CTA with atypical chest pain and clinical suspicion of CAD were included in the study. Quantification of CACS, epicardial fat volume (EFV) and epicardial fat attenuation (EFat) was performed on non-contrast images. CTA was evaluated for presence of obstructive CAD and presence of HRPF. RESULTS: 255 patients (median age [interquartile range; IQR]: 51[41-60] years, 51.8% males) were included. On CTA, CAD, obstructive CAD (≥50% stenosis) and CTA-derived HRPFs was present in 133 (52.2%), 37 (14.5%) and 82 (32.2%) patients respectively. A significantly lower EFat was seen in patients with obstructive CAD than in those without (-86HU [IQR:-88 to -82 HU] vs -84 [IQR:-87 HU to -82 HU]; p = 0.0486) and in patients with HRPF compared to those without (-86 HU [IQR:-88 to -83 HU] vs -83 HU [-86 HU to -81.750 HU]; p < 0.0001). EFat showed significant association with obstructive CAD (unadjusted Odd's ratio (OR) [95% CI]: 0.90 [0.81-0.99];p = 0.0248) and HRPF (unadjusted OR [95% CI]: 0.83 [0.76-0.90];p < 0.0001) in univariate analysis, which remained significant in multivariate analysis. However, EFV did not show any significant association with neither obstructive CAD nor HRPF in multivariate analysis. Adding EFat to conventional coronary risk factors and CACS in the pre-test probability models increased the area-under curve (AUC) for prediction of both obstructive CAD (AUC[95% CI]: 0.76 [0.70-0.81] vs 0.71 [0.65-0.77)) and HRPF (AUC [95% CI]: 0.92 [0.88-0.95] vs 0.89 [0.85-0.93]), although not reaching statistical significance. CONCLUSION: EFat, but not EFV, is an independent predictor of obstructive CAD and HRPF. Addition of EFat to traditional cardiovascular risk factors and CACS improves estimation for pretest probability of obstructive CAD and HRPF. ADVANCES IN KNOWLEDGE: EFat is an important attribute of epicardial fat as it reflects the "quality" of fat, taking into account the effects of brown-white fat transformation and fibrosis, as opposed to mere evaluation of "quantity" of fat by EFV. Our study shows that EFat is a better predictor of obstructive CAD and HRPF than EFV and can thus explain the inconsistent association of increased EFV alone with CAD.


Assuntos
Tecido Adiposo/patologia , Dor no Peito , Doença da Artéria Coronariana/patologia , Pericárdio/patologia , Placa Aterosclerótica/patologia , Tecido Adiposo/diagnóstico por imagem , Adulto , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
8.
Int. j. morphol ; 38(3): 737-746, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098314

RESUMO

This study aimed to evaluate changes in beige adipocytes at different times of melatonin administration, in the morning (ZT01) or in the evening (ZT11), at 30 mg/kg daily by gavage for 7 weeks or continuously with drinking water in the term of high-calorie diet-induced obesity (HCD). Melatonin received at ZT11 or with drinking water resulted in an increased area of the browning zone in the subcutaneous white adipose tissue (sWAT), even in rats with HCD (compared with Control or HCD, respectively). The beige adipocyte and lipid droplet area after melatonin use were reduced compared to those with HCD and Control, in all administration modes (group ZT01 showed smaller changes compared to ZT11 or with drinking water groups). The fibrosis level decreased and significantly differed in HCD ZT01, HCD ZT11, and HCD water compared to that in HCD; moreover, the lowest value determined in HCD water, reached the control parameters. Furthermore, the IL-1b and IL-8 level was decreased in the HCD groups under melatonin treatment at ZT11 or with drinking water compared to that in HCD. The obtained results suggest that melatonin promotes sWAT browning in rats with diet-induced obesity and influences morphological signs of normal rats depending on the time of administration. Different functional activity of beige adipocytes was observed after melatonin was used depending on the time of administration, resulting in heat production and lipolysis (the relative mass of visceral fat was likewise diminished). More rapid browning was observed when melatonin treatment was performed at 1 h before lights-off (ZT11) or continuously via drinking water. Melatonin acted on beige adipocytes of obese rats through changing some parameters such as the area of adipocytes and lipid drops, the number of lipid drops, the relative area browning of sWAT, and the level of tissue fibrosis.


Este estudio tuvo como objetivo evaluar los cambios en los adipocitos beige en diferentes momentos de la administración de melatonina, en la mañana (ZT01) o por la noche (ZT11). Se administraron 30 mg/kg diariamente por sonda durante 7 semanas o continuamente con agua potable durante el periodo de obesidad inducida por una dieta alta en calorías (HCD). La melatonina recibida en ZT11 o con agua potable resultó en un aumento de área dorada en tejido adiposo blanco subcutáneo (sWAT), incluso en ratas con HCD (en comparación con Control o HCD, respectivamente). El área de gotas de lípidos y adipocitos de color beige después del uso de melatonina se redujo en comparación con aquellos con HCD y Control, en todos los modos de administración (el grupo ZT01 mostró cambios más pequeños en comparación con ZT11 o con grupos de agua potable). El nivel de fibrosis disminuyó y difirió significativamente en HCD ZT01, HCD ZT11 y agua HCD, en comparación con el HCD; además, el valor más bajo determinado en agua HCD alcanzó los parámetros de control. Además, el nivel de IL-1b e IL-8 disminuyó en los grupos HCD bajo tratamiento con melatonina en ZT11 o con agua potable en comparación con el de HCD. Los resultados obtenidos sugieren que la melatonina promueve el dorado sWAT en ratas con obesidad inducida por la dieta e influye en los signos morfológicos de las ratas normales dependiendo del momento de la administración. Se observó una actividad funcional diferente de los adipocitos de color beige después de usar melatonina dependiendo del tiempo de administración, dando como resultado la producción de calor y lipólisis (la masa relativa de grasa visceral también disminuyó). Se observó un ennegrecimiento más rápido cuando el tratamiento con melatonina se realizó 1 h antes de apagar las luces (ZT11) o de forma continua en grupos de agua potable. La melatonina actuó en los adipocitos beige de ratas obesas al cambiar algunos parámetros, como el área de adipocitos y gotas de lípidos, el número de gotas de lípidos, el área relativa de ennegrecimiento de sWAT y el nivel de fibrosis tisular.


Assuntos
Animais , Masculino , Ratos , Adipócitos Bege/efeitos dos fármacos , Melatonina/administração & dosagem , Obesidade , Fatores de Tempo , Fibrose , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Interleucina-8/efeitos dos fármacos , Dieta , Interleucina-1beta/efeitos dos fármacos
9.
Lancet Diabetes Endocrinol ; 8(7): 616-627, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32559477

RESUMO

An increase in fat mass is considered to be an important risk factor for the worldwide increase in type 2 diabetes and cardiovascular disease. However, for a given fat mass, there is a large variability in the risk prediction of these cardiometabolic diseases. For example, some lean people unexpectedly have a risk of type 2 diabetes and cardiovascular disease that is similar to the increased risk that is observed in most people who have obesity. What both of these phenotypes have in common is a very characteristic fat distribution. As a result, much focus has been given on the strong predictive power of increased visceral fat mass. However, an analysis of the causes of type 2 diabetes and cardiovascular disease, as well as comparisons to rare diseases such as lipodystrophy and studying genetically determined fat distribution in the general population, suggest that an impaired ability to expand subcutaneous fat in the lower part of the body is also important for predicting the incidence of these cardiometabolic diseases. This Review, first, addresses the identification of distinct fat distribution phenotypes and their risk of cardiometabolic diseases by discussing findings from published studies that have applied precise quantification of different fat depots. Second, this Review provides support for the theory that a lower amount of lower-body fat mass is equally important to a high amount of visceral fat mass as a determinant of cardiometabolic diseases. Third, this Review discusses the genetic and lifestyle-related causes of metabolically healthy and unhealthy fat distribution. Finally, this Review summarises and appraises the effectiveness of lifestyle-related interventions and pharmacological interventions for reducing visceral adiposity and maintaining lower-body fat mass to prevent and treat cardiometabolic diseases.


Assuntos
Tecido Adiposo/patologia , Distribuição da Gordura Corporal , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Resistência à Insulina , Obesidade/complicações , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Fatores de Risco
10.
PLoS One ; 15(6): e0232972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32512581

RESUMO

Various dietary fibers are considered to prevent obesity by modulating the gut microbiota. Cordyceps sinensis polysaccharide (CSP) is a soluble dietary fiber known to have protective effects against obesity and related diseases, but whether these effects induce any side effects remains unknown. The function and safety of CSP were tested in high-fat diet (HFD)-feding C57BL/6J mice. The results revealed that even though CSP supplementation could prevent an increase in body weight, it aggravated liver fibrosis and steatosis as evidenced by increased inflammation, lipid metabolism markers, insulin resistance (IR) and alanine aminotransferase (ALT) in HFD-induced obesity. 16S rDNA gene sequencing was used to analyze the gut microbiota composition, and the relative abundance of the Actinobacteria phylum, including the Olsenella genus, was significantly higher in CSP-treated mice than in HFD-fed mice. CSP supplementation may increase the proportion of Actinobacteria, which can degrade CSP. The high level of Actinobacteria aggravated the disorder of the intestinal flora and contributed to the progression from obesity to nonalcoholic steatohepatitis (NASH) and related diseases.


Assuntos
Cordyceps , Dieta Hiperlipídica/efeitos adversos , Fibras na Dieta/administração & dosagem , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica/metabolismo , Polissacarídeos/administração & dosagem , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Peso Corporal , Cordyceps/metabolismo , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/metabolismo , Resistência à Insulina , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia , Polissacarídeos/isolamento & purificação
11.
PLoS One ; 15(6): e0228521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544198

RESUMO

BACKGROUND AND AIMS: Adipose tissue plays a pivotal role in storing excess fat and its composition reflects the history of person's lifestyle and metabolic health. Broad profiling of lipids with mass spectrometry has potential for uncovering new knowledge on the pathology of obesity, metabolic syndrome, diabetes and other related conditions. Here, we developed a lipidomic method for analyzing human subcutaneous adipose biopsies. We applied the method to four body areas to understand the differences in lipid composition between these areas. MATERIALS AND METHODS: Adipose tissue biopsies from 10 participants were analyzed using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The sample preparation optimization included the optimization of the lipid extraction, the sample amount and the sample dilution factor to detect lipids in an appropriate concentration range. Lipidomic analyses were performed for adipose tissue collected from the abdomen, breast, thigh and lower back. Differences in lipid levels between tissues were visualized with heatmaps. RESULTS: Lipidomic analysis on human adipose biopsies lead to the identification of 186lipids in 2 mg of sample. Technical variation of the lipid-class specific internal standards were below 5%, thus indicating acceptable repeatability. Triacylglycerols were highly represented in the adipose tissue samples, and lipids from 13 lipid classes were identified. Long polyunsaturated triacylglycerols in higher levels in thigh (q<0.05), when compared with the abdomen, breast and lower back, indicating that the lipidome was area-specific. CONCLUSION: The method presented here is suitable for the analysis of lipid profiles in 2 mg of adipose tissue. The amount of fat across the body is important for health but we argue that also the distribution and the particular profile of the lipidome may be relevant for metabolic outcomes. We suggest that the method presented in this paper could be useful for detecting such aberrations.


Assuntos
Tecido Adiposo/metabolismo , Lipidômica , Tecido Adiposo/patologia , Biópsia , Humanos , Especificidade de Órgãos
12.
Acta Cir Bras ; 35(4): e202000403, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578723

RESUMO

PURPOSE: To collect data capable of pointing out the effects of the ultracavitation treatment on the liver of rabbits after adipose tissue application, by means of histological analyses of the liver and hematological and biochemical exams. METHODS: This is an experimental study with 12 albino rabbits as sample, which were divided into 3 groups and submitted to a hypercaloric diet for one month. Subsequently, subjects underwent UCV treatment: 3 minutes, 30 W, continuous mode at 100%, every 2 ERAS = 441.02 J/cm2, intensity of 10w/cm2. They were then euthanized and underwent biopsy after 24 hours. RESULTS: After 48 hours from the ultracavitation treatment, the animals' livers presented greater amount of fat infiltration if compared to the amount presented 96 hours after the treatment. However, laboratory tests showed no alterations. Values were maintained within normal parameters of cholesterol, triglycerides, liver enzymes, hemoglobin and hematocrit levels. CONCLUSIONS: This study has identified that infiltrates may appear on livers after the treatment, despite high hematological and biochemical tests results. The fat infiltrates reduction 96 h after treatment suggests lower risks to animal health, if the period between applications is respected.


Assuntos
Tecido Adiposo/patologia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Lipodistrofia/patologia , Lipodistrofia/terapia , Fígado/patologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Colesterol/sangue , Feminino , Hematócrito , Hemoglobinas/análise , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Lipodistrofia/sangue , Masculino , Coelhos , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue
13.
PLoS One ; 15(6): e0234061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32484835

RESUMO

Here we present a secondary analysis from a parent database of 97 acutely injured participants enrolled in a prospective inception cohort study of whiplash recovery after motor vehicle collision (MVC). The purpose was to investigate the deep and superficial neck extensor muscles with peri-traumatic computed tomography (CT) and longitudinal measures of magnetic resonance imaging (MRI) in participants with varying levels of whiplash-related disability. Thirty-six underwent standard care imaging of the cervical spine with CT at a level-1 trauma designated emergency department. All 36 participants were assessed with MRI of the cervical spine at <1-week, 2-weeks, 3-, and 12-months post-injury and classified into three groups using initial pain severity and percentage scores on the Neck Disability Index (recovered (NDI of 0-8%), mild (NDI of 10-28%), or severe (NDI ≥ 30%)) at 3-months post MVC. CT muscle attenuation values were significantly correlated to muscle fat infiltration (MFI) on MRI at one-week post MVC. There was no significant difference in muscle attenuation across groups at the time of enrollment. A trend of lower muscle attenuation in the deep compared to the superficial extensors was observed in the severe group. MFI values in the deep muscles on MRI were significantly higher in the severe group when compared to the mild group at 1-year post MVC. This study provides further evidence that the magnitude of 1) deep MFI appears unique to those at risk of and eventually transitioning to chronic WAD and that 2) pre- or peri-traumatic muscular health, determined by CT muscle attenuation, may be contribute to our understanding of long-term recovery.


Assuntos
Tecido Adiposo/patologia , Imagem por Ressonância Magnética , Músculos/patologia , Tomografia Computadorizada por Raios X , Traumatismos em Chicotada/diagnóstico por imagem , Traumatismos em Chicotada/patologia , Adulto , Pessoas com Deficiência , Feminino , Humanos , Masculino , Dor/complicações , Autorrelato , Traumatismos em Chicotada/complicações
14.
Am J Pathol ; 190(9): 1909-1920, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32533926

RESUMO

Perivascular mural cells surround capillaries and microvessels and have diverse regenerative or fibrotic functions after tissue injury. Subsynovial fibrosis is a well-known pathologic feature of osteoarthritis, yet transgenic animals for use in visualizing perivascular cell contribution to fibrosis during arthritic changes have not been developed. Here, inducible Pdgfra-CreERT2 reporter mice were subjected to joint-destabilization surgery to induce arthritic changes, and cell lineage was traced over an 8-week period with a focus on the joint-associated fat pad. Results showed that, at baseline, inducible Pdgfra reporter activity highlighted adventitial and, to a lesser extent, pericytic cells within the infrapatellar fat pad. Joint-destabilization surgery was associated with marked fibrosis of the infrapatellar fat pad, accompanied by an expansion of perivascular Pdgfra-expressing cellular descendants, many of which adopted α-smooth muscle actin expression. Gene expression analysis of microdissected infrapatellar fat pad confirmed enrichment in membrane-bound green fluorescent protein/Pdgfra-expressing cells, along with a gene signature that corresponded with injury-associated fibro-adipogenic progenitors. Our results highlight dynamic changes in joint-associated perivascular fibro-adipogenic progenitors during osteoarthritis.


Assuntos
Adipócitos/patologia , Fibroblastos/patologia , Osteoartrite/patologia , Tecido Adiposo/patologia , Animais , Linhagem da Célula , Articulação do Joelho/patologia , Camundongos , Camundongos Transgênicos , Células-Tronco
15.
Allergol. immunopatol ; 48(3): 306-312, mayo-jun. 2020. ilus
Artigo em Inglês | IBECS | ID: ibc-192034

RESUMO

Over the past three decades, the number of obese people has risen steadily. The chronic low-grade inflammatory state and the non-specific activation of the immune system have contributed greatly to the development of obesity-related immunology. Food allergy as a kind of inflammatory disease with abnormal immune response may be associated with obesity. This review begins with the pro-inflammatory immunological effects of adipose tissue in obesity, and explains the possible effects of obesity on food allergy. In short, obesity not only directly causes imbalance of allergic-related immune cells in adipose tissue, but also indirectly causes this consequence through affecting expression of adipocytokines and peroxisome proliferator-activated receptor gamma (PPARγ) in adipose tissue. As a result, circulating levels of pro-inflammatory factors which are partly derived from adipose tissue increase, which might cause intestinal barrier injury. Therefore, obesity may increase the risk of food allergy


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Assuntos
Humanos , Tecido Adiposo/imunologia , Hipersensibilidade Alimentar/diagnóstico , Obesidade/complicações , Hipersensibilidade Alimentar/metabolismo , Inflamação/etiologia , Hipersensibilidade Alimentar/imunologia , Obesidade/imunologia , Tecido Adiposo/patologia
16.
Obesity (Silver Spring) ; 28(7): 1292-1300, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568462

RESUMO

OBJECTIVE: Lipedema is characterized by pain, fatigue, and excessive adipose tissue and sodium accumulation of the lower extremities. This case-control study aims to determine whether sodium or vascular dysfunction is present in the central nervous system. METHODS: Brain magnetic resonance imaging was performed at 3 T in patients with lipedema (n = 15) and control (n = 18) participants matched for sex, age, race, and BMI. Standard anatomical imaging and intracranial angiography were applied to evaluate brain volume and vasculopathy, respectively; arterial spin labeling and sodium magnetic resonance imaging were applied to quantify cerebral blood flow (CBF) (milliliters per 100 grams of tissue/minute) and brain tissue sodium content (millimoles per liter), respectively. A Mann-Whitney U test (significance criteria P < 0.05) was applied to evaluate group differences. RESULTS: No differences in tissue volume, white matter hyperintensities, intracranial vasculopathy, or tissue sodium content were observed between groups. Gray matter CBF was elevated (P = 0.03) in patients with lipedema (57.2 ± 9.6 mL per 100 g/min) versus control participants (49.8 ± 9.1 mL per 100 g/min). CONCLUSIONS: Findings provide evidence that brain sodium and tissue fractions are similar between patients with lipedema and control participants and that patients with lipedema do not exhibit abnormal radiological indicators of intracranial vasculopathy or ischemic injury. Potential explanations for elevated CBF are discussed in the context of the growing literature on lipedema symptomatology and vascular dysfunction.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Lipedema/metabolismo , Lipedema/fisiopatologia , Sódio/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Química Encefálica/fisiologia , Estudos de Casos e Controles , Feminino , Humanos , Lipedema/diagnóstico , Lipedema/psicologia , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Neuroimagem/métodos , Sódio/análise
17.
Cardiovasc Pathol ; 48: 107224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32480283

RESUMO

OBJECTIVE: We used automated image analysis software to determine the proportion of collagen, fat, and myocytes across six histological regions of normal ventricular myocardium. METHODS: Twenty-nine non-cardiac death cases referred to our national cardiac pathology center were included in this study. Whole hearts were macroscopically and microscopically normal following expert histopathological evaluation. Tissue sections from the right ventricular outflow tract, right ventricle (RV), anterior interventricular septum (IVS), posterior IVS, anterior left ventricle (LV), and posterior LV were stained with Picrosirius red for collagen and scanned using a high-resolution slide scanner. Quantification of collagen, fat, and myocyte proportions was performed using Visiopharm software after automated exclusion of perivascular collagen. RESULTS: The majority of decedents were male (25/29; 86%) with a mean age at death of 32.1 ± 9.9 (range 18-54) and mean BMI 28.7 ± 7.3. We report predicted values (collagen %, fat %, myocytes %) for cardiac tissue composition within the RV, IVS, and LV (including epicardial and endocardial layers). The proportion of collagen and fat were higher in the RV compared with the LV (ratios 1.61 [1.45-1.78]; 2.63 [1.99-3.48], respectively) and RV compared with the IVS (ratios 1.77 [1.60-1.97]; 8.41[6.35-11.13], respectively). The ratio of epicardial versus endocardial fat was increased in both ventricles (RV: ratio 4.49 [3.67-5.49]; LV: ratio 3.46 [2.49-4.81]). In multivariable analysis, there was no significant association between collagen or fat proportion and sex (p=0.12; p=0.08, respectively), age at death (p=0.36; p=0.23, respectively), or BMI (p=0.45; p=0.43, respectively). CONCLUSIONS: Our findings provide location and sex-specific proportions of myocardial histological tissue composition that may aid quantitative evaluation of pathology in future studies.


Assuntos
Tecido Adiposo/patologia , Colágeno/análise , Ventrículos do Coração/química , Ventrículos do Coração/patologia , Miócitos Cardíacos/química , Miócitos Cardíacos/patologia , Adolescente , Adulto , Autopsia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
18.
Clin Sci (Lond) ; 134(12): 1403-1432, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32556180

RESUMO

Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.


Assuntos
Tecido Adiposo/patologia , Aterosclerose/tratamento farmacológico , Flavonoides/uso terapêutico , Inflamação/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aterosclerose/complicações , Flavonoides/química , Flavonoides/farmacologia , Humanos , Inflamação/complicações , Modelos Biológicos
19.
Clin Sci (Lond) ; 134(12): 1473-1474, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32579179

RESUMO

Adipose biology research has grown rapidly offering new insights into the physiological and pathophysiological roles of different body fat depots. This Thematic Collection of Clinical Science brings a well-rounded timely view of the recent development in this field. We highlight the state of the art on adipose tissue function/dysfunction in the context of cardiovascular and metabolic pathologies.


Assuntos
Tecido Adiposo/patologia , Doenças Cardiovasculares/patologia , Terapia de Alvo Molecular , Adipocinas/metabolismo , Humanos , Inflamação/patologia
20.
PLoS One ; 15(5): e0233152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453755

RESUMO

Obesity is associated with significantly higher mortality rates, and excess adipose tissue is involved in respective pathologies. Here we established a human adipose tissue slice cultures (HATSC) model ex vivo. HATSC match the in vivo cell composition of human adipose tissue with, among others, mature adipocytes, mesenchymal stem cells as well as stroma tissue and immune cells. This is a new method, optimized for live imaging, to study adipose tissue and cell-based mechanisms of obesity in particular. HATSC survival was tested by means of conventional and immunofluorescence histological techniques, functional analyses and live imaging. Surgery-derived tissue was cut with a tissue chopper in 500 µm sections and transferred onto membranes building an air-liquid interface. HATSC were cultured in six-well plates filled with Dulbecco's Modified Eagle's Medium (DMEM), insulin, transferrin, and selenium, both with and without serum. After 0, 1, 7 and 14 days in vitro, slices were fixated and analyzed by morphology and Perilipin A for tissue viability. Immunofluorescent staining against IBA1, CD68 and Ki67 was performed to determine macrophage survival and proliferation. These experiments showed preservation of adipose tissue as well as survival and proliferation of monocytes and stroma tissue for at least 14 days in vitro even in the absence of serum. The physiological capabilities of adipocytes were functionally tested by insulin stimulation and measurement of Phospho-Akt on day 7 and 14 in vitro. Viability was further confirmed by live imaging using Calcein-AM (viable cells) and propidium iodide (apoptosis/necrosis). In conclusion, HATSC have been successfully established by preserving the monovacuolar form of adipocytes and surrounding macrophages and connective tissue. This model allows further analysis of mature human adipose tissue biology ex vivo.


Assuntos
Adipócitos , Tecido Adiposo , Modelos Biológicos , Obesidade , Técnicas de Cultura de Tecidos , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adolescente , Adulto , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Sobrevivência Celular , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/patologia
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