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1.
J Am Soc Cytopathol ; 13(3): 219-226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38493005

RESUMO

INTRODUCTION: Fine-needle aspiration (FNA) of abdominal fibroadipose tissue is a commonly utilized method for the detection of amyloidosis. While generally regarded as an accurate and specific detection method, the sensitivity is variable. The objective of this study was to investigate the performance of fat pad FNAs in detecting amyloidosis relative to other tissue biopsies. MATERIALS AND METHODS: Fat pad FNA results from January 1, 2014, to December 31, 2022, were catalogued. Clinical data including FNA indication were ascertained for each case. The results of any subsequent tissue biopsy/biopsies evaluated for amyloidosis by Congo red staining were also assessed. Challenges to diagnostic interpretation were explored. RESULTS: A total of 334 fat pad FNAs were identified. The most common indications were peripheral neuropathy (29.3%), cardiomyopathy/heart failure (28.1%), monoclonal gammopathy (27.8%), and multiple myeloma/lymphoplasmacytic lymphoma (21.0%). Cytologic interpretations were: 7 (2.1%) nondiagnostic, 284 (85.0%) negative, 18 (5.4%) indeterminate, 16 (4.8%) suspicious, and 9 (2.7%) positive for amyloid deposition. In our sample, 103 (30.8%) patients had Congo red testing performed on a subsequent surgical specimen(s) including: 3 of 7 of nondiagnostic cases, none which were positive on the subsequent surgical; 70 of 284 negative cases, 27 which were positive on the subsequent surgical; 11 of 18 indeterminate cases, 7 which were positive on the subsequent surgical; 13 of 16 suspicious cases, 2 which were positive on the subsequent surgical; and 6 of 9 positive cases, 3 which were positive on the subsequent surgical. Challenges to FNA interpretation included scant cellularity, focal staining/birefringence, and overstaining. CONCLUSIONS: It is best to view fat pad aspiration versus other tissue biopsy results as complimentary diagnostic tests that should be interpreted in the context of the clinical setting and overall clinical suspicion for amyloidosis.


Assuntos
Gordura Abdominal , Amiloidose , Humanos , Biópsia por Agulha Fina/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Amiloidose/patologia , Amiloidose/diagnóstico , Idoso , Gordura Abdominal/patologia , Adulto , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Sensibilidade e Especificidade
2.
Int Heart J ; 63(1): 49-55, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35095076

RESUMO

The diagnosis of cardiac amyloidosis is frequently delayed because histological confirmation is often challenging. Few studies have attempted to clarify the utility and safety of abdominal fat pad fine-needle aspiration (FPFNA) for an initial screening test in patients with suspected cardiac amyloidosis.This study included 77 consecutive patients with suspected non-ischemic cardiomyopathy who had left ventricular dysfunction and/or hypertrophy. All patients underwent abdominal FPFNA and an endomyocardial biopsy. In all patients, the abdominal FPFNA could be performed within less than 5 minutes with no complications; however, in 1 patient (1.3%), the obtained specimen was too small to evaluate. Among the remaining 76 patients, 5 (6.6%) were positive for amyloid (FPFNA[+]) and 7 (9.2%), including the 5 FPFNA[+], were diagnosed with cardiac amyloidosis (AL = 1, ATTR = 6) by endomyocardial biopsy. Positive abdominal FPFNAs indicated cardiac amyloidosis with high accuracy (sensitivity, 71.4%; specificity, 100%).Positive abdominal FPFNAs are directly linked to diagnoses of cardiac amyloidosis. Abdominal FPFNA is simple and useful for the initial screening test for cardiac amyloidosis in patients with non-ischemic cardiomyopathy.


Assuntos
Gordura Abdominal/patologia , Amiloidose/diagnóstico , Biópsia por Agulha Fina , Cardiopatias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Endocárdio/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Volume Sistólico
3.
Diabetes ; 71(3): 381-393, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34857544

RESUMO

The role of adipose tissue (AT) inflammation in AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression, and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC50). We studied 86 volunteers with normal weight or obesity at baseline and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong positive relationship between IC50 and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC50 and abdominal AT inflammatory markers CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6, and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC50; however, there was no reduction in adipose ATM content, senescent cells, or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.


Assuntos
Tecido Adiposo/fisiopatologia , Inflamação/fisiopatologia , Resistência à Insulina/fisiologia , Obesidade/fisiopatologia , Gordura Abdominal/patologia , Gordura Abdominal/fisiopatologia , Adipócitos/patologia , Tecido Adiposo/patologia , Adulto , Glicemia/metabolismo , Tamanho Celular , Senescência Celular , Citocinas/análise , Citocinas/genética , Feminino , Expressão Gênica , Humanos , Inflamação/patologia , Insulina/sangue , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Redução de Peso/fisiologia
4.
Front Endocrinol (Lausanne) ; 12: 697223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566888

RESUMO

Background: Women with polycystic ovary syndrome (PCOS) are generally considered to be central obese and at higher risks of metabolic disturbances. Imaging methods are the golden standards for detecting body fat distribution. However, evidence based on magnetic resonance imaging (MRI) and computed tomography (CT) is conflicting. This study systematically reviewed the imaging-based body fat distribution in PCOS patients and quantitatively evaluated the difference in body fat distribution between PCOS and BMI-matched controls. Methods: PUBMED, EMBASE, and Web of Science were searched up to December 2019, and studies quantitatively compared body fat distribution by MRI, CT, ultrasound, or X-ray absorptiometry (DXA) between women with PCOS and their BMI-matched controls were included. Two researchers independently reviewed the articles, extract data and evaluated the study quality based on Newcastle-Ottawa Scale (NOS). Results: 47 studies were included in systematic review and 39 were eligible for meta-analysis. Compared to BMI-matched controls, higher accumulations of visceral fat (SMD 0.41; 95%CI: 0.23-0.59), abdominal subcutaneous fat (SMD 0.31; 95%CI: 0.20-0.41), total body fat (SMD 0.19; 95% CI: 0.06-0.32), trunk fat (SMD 0.47; 95% CI: 0.17-0.77), and android fat (SMD 0. 36; 95% CI: 0.06-0.66) were identified in PCOS group. However, no significant difference was identified in all the above outcomes in subgroups only including studies using golden standards MRI or CT to evaluate body fat distribution (SMD 0.19; 95%CI: -0.04-0.41 for visceral fat; SMD 0.15; 95%CI: -0.01-0.31 for abdominal subcutaneous fat). Moreover, meta-regression and subgroup analyses showed that young and non-obese patients were more likely to accumulate android fat. Conclusions: PCOS women seem to have abdominal fat accumulation when compared with BMI-matched controls. However, MRI- and CT- assessed fat distribution was similar between PCOS and controls, suggesting central obesity may be independent of PCOS. These findings will help us reappraise the relationship between PCOS and abnormal fat deposition and develop specialized lifestyle interventions for PCOS patients. Systematic Review Registration: PROSPERO, identifier CRD42018102983.


Assuntos
Distribuição da Gordura Corporal , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Gordura Abdominal/diagnóstico por imagem , Gordura Abdominal/patologia , Índice de Massa Corporal , Estudos de Casos e Controles , Diagnóstico por Imagem/métodos , Feminino , Humanos , Resistência à Insulina , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/metabolismo , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/fisiopatologia
5.
J Clin Endocrinol Metab ; 106(11): e4438-e4447, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34181708

RESUMO

CONTEXT: Weight gain during adulthood increases cardiometabolic disease risk, possibly through adipocyte hypertrophy. OBJECTIVE: We aimed to study the specific metabolomic profile of adult weight gain, and to examine its association with adipocyte volume. METHODS: Nuclear magnetic resonance-based metabolomics were measured in the Netherlands Epidemiology of Obesity (NEO) study (n = 6347, discovery) and Oxford Biobank (n = 6317, replication). Adult weight gain was calculated as the absolute difference between body mass index (BMI) at middle age and recalled BMI at age 20 years. We performed linear regression analyses with both exposures BMI at age 20 years and weight gain, and separately with BMI at middle age in relation to 149 serum metabolomic measures, adjusted for age, sex, and multiple testing. Additionally, subcutaneous abdominal adipocyte biopsies were collected in a subset of the Oxford Biobank (n = 114) to estimate adipocyte volume. RESULTS: Mean (SD) weight gain was 4.5 (3.7) kg/m2 in the NEO study and 3.6 (3.7) kg/m2 in the Oxford Biobank. Weight gain, and not BMI at age 20 nor middle age, was associated with concentrations of 7 metabolomic measures after successful replication, which included polyunsaturated fatty acids, small to medium low-density lipoproteins, and total intermediate-density lipoprotein. One SD weight gain was associated with 386 µm3 (95% CI, 143-629) higher median adipocyte volume. Adipocyte volume was associated with lipoprotein particles specific for adult weight gain. CONCLUSION: Adult weight gain is associated with specific metabolomic alterations of which the higher lipoprotein concentrations were likely contributed by larger adipocyte volumes, presumably linking weight gain to cardiometabolic disease.


Assuntos
Adipócitos/patologia , Metaboloma/fisiologia , Aumento de Peso/fisiologia , Gordura Abdominal/patologia , Envelhecimento , Biópsia , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Lipoproteínas/sangue , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Obesidade/epidemiologia
6.
Am J Physiol Endocrinol Metab ; 321(1): E105-E121, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33998291

RESUMO

Obesity is accompanied by numerous systemic and tissue-specific derangements, including systemic inflammation, insulin resistance, and mitochondrial abnormalities in skeletal muscle. Despite growing recognition that adipose tissue dysfunction plays a role in obesity-related disorders, the relationship between adipose tissue inflammation and other pathological features of obesity is not well-understood. We assessed macrophage populations and measured the expression of inflammatory cytokines in abdominal adipose tissue biopsies in 39 nondiabetic adults across a range of body mass indexes (BMI 20.5-45.8 kg/m2). Skeletal muscle biopsies were used to evaluate mitochondrial respiratory capacity, ATP production capacity, coupling, and reactive oxygen species production. Insulin sensitivity (SI) and ß cell responsivity were determined from test meal postprandial glucose, insulin, c-peptide, and triglyceride kinetics. We examined the relationships between adipose tissue inflammatory markers, systemic inflammatory markers, SI, and skeletal muscle mitochondrial physiology. BMI was associated with increased adipose tissue and systemic inflammation, reduced SI, and reduced skeletal muscle mitochondrial oxidative capacity. Adipose-resident macrophage numbers were positively associated with circulating inflammatory markers, including tumor necrosis factor-α (TNFα) and C-reactive protein (CRP). Local adipose tissue inflammation and circulating concentrations of TNFα and CRP were negatively associated with SI, and circulating concentrations of TNFα and CRP were also negatively associated with skeletal muscle oxidative capacity. These results demonstrate that obese humans exhibit increased adipose tissue inflammation concurrently with increased systemic inflammation, reduced insulin sensitivity, and reduced muscle oxidative capacity and suggest that adipose tissue and systemic inflammation may drive obesity-associated metabolic derangements.NEW AND NOTEWORTHY Adipose inflammation is proposed to be at the nexus of the systemic inflammation and metabolic derangements associated with obesity. The present study provides evidence to support adipose inflammation as a central feature of the pathophysiology of obesity. Adipose inflammation is associated with systemic and peripheral metabolic derangements, including increased systemic inflammation, reduced insulin sensitivity, and reduced skeletal muscle mitochondrial respiration.


Assuntos
Gordura Abdominal/patologia , Inflamação/patologia , Resistência à Insulina , Macrófagos/patologia , Obesidade/patologia , Gordura Abdominal/química , Gordura Abdominal/metabolismo , Adulto , Biomarcadores/análise , Índice de Massa Corporal , Proteína C-Reativa/análise , Contagem de Células , Citocinas/análise , Feminino , Expressão Gênica , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/metabolismo , Obesidade/fisiopatologia , Consumo de Oxigênio , Fator de Necrose Tumoral alfa/sangue
7.
PLoS One ; 16(4): e0250337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909662

RESUMO

OBJECTIVES: The study aimed to examine the effect of focused ultrasound cavitation augmented with aerobic exercise on localized abdominal and intrahepatic fat in fatty liver patients. METHODS: 34 fatty liver patients aged 30-45 with a body mass index (BMI) of 30-40 kg/m2 were randomly assigned into two equally numbered groups. Group A received focused ultrasound cavitation and moderate aerobic exercise for three months, while Group B (control group) received moderate aerobic exercise only. Abdominal subcutaneous fat volume, visceral fat volume, liver-to-spleen ratio (L/S ratio), body weight, BMI, and waist circumference were measured both before and after the study period. RESULTS: Both groups showed significant improvements in subcutaneous fat volume, visceral fat volume, body weight, BMI, and waist circumference relative to baseline where (P < 0.001), with a higher percentage in group A. L/S ratio only showed a significant improvement in group A. Between-group differences were noteworthy regarding L/S ratio and waist circumference where (P < 0.0001). CONCLUSION: While substantial risky measures in non-alcoholic fatty liver disease have been modified by aerobic exercise, its combination with focused ultrasound cavitation causes more notable effects on the reduction of abdominal and intrahepatic fat, making it a superior option. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04161703.


Assuntos
Gordura Abdominal/cirurgia , Tecido Adiposo/cirurgia , Exercício Físico/fisiologia , Lipectomia/métodos , Fígado/cirurgia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Terapia por Ultrassom/métodos , Gordura Abdominal/diagnóstico por imagem , Gordura Abdominal/patologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Baço/diagnóstico por imagem , Baço/patologia , Tomografia Computadorizada por Raios X , Ondas Ultrassônicas , Circunferência da Cintura
8.
PLoS One ; 16(3): e0248856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33739984

RESUMO

AIMS: Metabolic syndrome (MetS) increases the risk of diabetes mellitus (DM), cardiovascular disease (CVD), cancer, and mortality. Sarcopenia has been reported as a risk factor for MetS, non-alcoholic fatty liver disease, and CVD. To date, the association between sarcopenia and MetS has been investigated. However, there have been few studies on the dose-response relationship between sarcopenia and MetS. We investigated the association between sarcopenia and the prevalence of MetS. We also aimed to analyze the dose-response relationship between skeletal muscle mass and the prevalence of MetS. METHODS: We enrolled 13,620 participants from October 2014 to December 2019. Skeletal muscle mass was measured using bioelectrical impedance analysis (BIA). Appendicular skeletal muscle mass (ASM) was divided by body weight (kg) and was expressed as a percentage (ASM x 100/Weight, ASM%). The quartiles of ASM% were calculated for each gender, with Q1 and Q4 being the lowest and highest quartiles of ASM%, respectively. The quartiles of ASM% were calculated for each gender, with Q1 and Q4 being the lowest and highest quartiles of ASM%, respectively. Linear regression and logistic regression analyses were used to compare the clinical parameters according to ASM%, adjusted for age, sex, obesity, hypertension (HT), DM, dyslipidemia (DL), smoking, alcohol intake, and C-reactive protein (CRP). Multiple logistic regression analysis was performed to determine the risk of MetS in each group. RESULTS: A dose-response relationship was identified between ASM% and MetS. Sarcopenia was associated with an increased prevalence of MetS. After adjustment for age, sex, obesity, HT, DM, DL, smoking, alcohol intake, and CRP, sarcopenia remained significantly associated with MetS. For each 1 quartile increment in ASM%, the risk of MetS decreased by 56% (P< 0.001). After adjusting for age, sex, obesity, HT, DM, DL, smoking, alcohol intake, and CRP, the risk of MetS decreased by 25% per 1Q increment in ASM% (P < 0.001). CONCLUSIONS: Sarcopenia by BIA is independently associated with the risk of MetS and has a dose-response relationship.


Assuntos
Síndrome Metabólica/complicações , Sarcopenia/complicações , Gordura Abdominal/diagnóstico por imagem , Gordura Abdominal/patologia , Adulto , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Músculos/diagnóstico por imagem , Músculos/patologia , Tamanho do Órgão , Prevalência , Sarcopenia/epidemiologia , Tomografia Computadorizada por Raios X
9.
Clin Nephrol ; 95(4): 201-207, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33433320

RESUMO

OBJECTIVE: Electron microscopy (EM) was used to observe the deposition and ultrastructural characteristics of amyloids in abdominal adipose tissue, which provided a reliable basis for pathological diagnosis of systemic amyloidosis. MATERIALS AND METHODS: 42 patients with established amyloidosis and 8 controls underwent surgical biopsy of subcutaneous abdominal fat. The fat tissues were submitted concurrently in 4% buffered neutral formalin for histological sections preparation, in glutaraldehyde fixative for EM studies, and in saline solutions for immunofluorescence tests. RESULTS: Light microscopy revealed marked brick-red staining in 11 of 42 samples, 6 moderate and 11 slight staining in the septum of cells, medium and small sized vessel, and apple green double refraction under polarized light microscopy. There were no significant differences in fat biopsies between the systemic amyloidosis and normal subjects in 14 cases. The EM showed approximate 10-nm-thick straight filaments in adipose tissue in all 42 cases with amyloidosis. The positive rate of diagnosis was 100%. Congo red stained sections alone in cases with scant amyloid led to false negative results, but the EM was able to characterize the amyloid protein in all cases. CONCLUSION: Therefore, preliminary diagnosis of suspected cases can be made by Congo red staining, but the final diagnosis requires an electron microscopic examination.


Assuntos
Gordura Abdominal , Amiloidose , Biópsia/métodos , Microscopia Eletrônica/métodos , Gordura Abdominal/diagnóstico por imagem , Gordura Abdominal/patologia , Amiloide/química , Amiloidose/diagnóstico por imagem , Amiloidose/patologia , Humanos
10.
Am J Kidney Dis ; 77(1): 44-55, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32798563

RESUMO

RATIONALE & OBJECTIVES: Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Participants with stages 3-5 CKD not receiving maintenance dialysis, followed up at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort (CRIC) Study, and who underwent magnetic resonance imaging of the abdomen at an annual CRIC Study visit (n = 419). PREDICTORS: VAT volume, SAT volume, intrahepatic fat, body mass index, waist circumference, and time taken to complete the 400-m walk test (physical function). OUTCOMES: Markers of inflammation (interleukin 1ß [IL-1ß], IL-6, tumor necrosis factor receptor 1 [TNFR1], and TNFR2), insulin resistance (homeostasis model assessment of insulin resistance), and adipokine levels (adiponectin, total and high molecular weight, resistin, and leptin). ANALYTICAL APPROACH: Multivariable linear regression of VAT and SAT volume, intrahepatic fat, and physical function with individual markers (log-transformed values), adjusting for relevant covariates. RESULTS: Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2±14.6 (SD) mL/min/1.73m2. More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors. LIMITATIONS: Lack of longitudinal data and dietary details. CONCLUSIONS: Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted.


Assuntos
Gordura Abdominal , Fatores Imunológicos/sangue , Inflamação/sangue , Resistência à Insulina , Desempenho Físico Funcional , Insuficiência Renal Crônica , Gordura Abdominal/metabolismo , Gordura Abdominal/patologia , Biomarcadores/sangue , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco/métodos , Estados Unidos/epidemiologia
11.
Diabetologia ; 64(1): 159-167, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001232

RESUMO

AIMS/HYPOTHESIS: In vitro and rodent studies suggest that pioglitazone, a thiazolidinedione, can promote adipogenesis in adipose tissue (AT); however, there is a lack of in vivo studies in humans to support these findings. The objectives of this randomised, placebo-controlled, parallel-arm trial were to test if pioglitazone stimulates in vivo adipogenesis in the subcutaneous adipose tissue depots and if these measures were related to metabolic health outcomes in women with obesity. METHODS: Forty-one healthy women with obesity (20 black; 21 white; 29 ± 6 years; BMI 32.0 ± 1.7 kg/m2; 44.0 ± 3.6% body fat) were randomised to consume 30 mg/day of pioglitazone (n = 21) or placebo (n = 20) for 16 weeks. SAS v9.4 was used to generate the block randomisation code sequence (stored in password-protected files) with a 1:1 allocation ratio. The participants and study staff involved in assessing and analysing data outcomes were blinded to the group assignments. The trial was conducted at Pennington Biomedical Research Center and ended in 2016. At baseline and post-intervention, subcutaneous abdominal (scABD) and femoral (scFEM) AT biopsies were collected, and in vivo cellular kinetics (primary endpoint of the trial) were assessed by an 8 week labelling protocol of deuterium (2H) into the DNA of adipose cells. Body composition was measured by dual-energy x-ray absorptiometry (DXA), scABD and visceral AT (VAT) by MRI, ectopic fat by 1H-MRS, and insulin sensitivity by an OGTT. RESULTS: After the 16 week intervention, there was a significant decrease in visceral fat (VAT:total abdominal AT [as a %]; p = 0.002) and an increase in the Matsuda index (i.e. improved insulin sensitivity; p = 0.04) in the pioglitazone group relative to the placebo group. A significant increase in the formation of new adipocytes was observed in the scFEM (Δ = 3.3 ± 1.6%; p = 0.04) but not the scABD depot (Δ = 2.0 ± 2.1%; p = 0.32) in the pioglitazone group relative to the placebo group. No serious adverse events were reported. CONCLUSIONS/INTERPRETATION: Pioglitazone may elicit distinct differences in in vivo adipogenesis in subcutaneous adipose depots in women with obesity, with increased rates in the protective scFEM. Trial registration ClinicalTrials.gov NCT01748994 Funding This study was funded by R01DK090607, P30DK072476, and R03DK112006 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health. The Robert C. and Veronica Atkins Foundation. Graphical abstract.


Assuntos
Adipogenia/efeitos dos fármacos , Obesidade/patologia , Pioglitazona/administração & dosagem , Gordura Abdominal/efeitos dos fármacos , Gordura Abdominal/patologia , Adipócitos/patologia , Adulto , Biópsia , População Negra , Composição Corporal , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/patologia , Obesidade/metabolismo , Placebos , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/patologia , Relação Cintura-Quadril , População Branca
12.
Fertil Steril ; 116(1): 232-242, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33341231

RESUMO

OBJECTIVE: To examine whether subcutaneous (SC) abdominal adipose stem cell differentiation into adipocytes in vitro predicts insulin sensitivity (Si) in vivo in normal-weight women with polycystic ovary syndrome (PCOS) and controls. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENT(S): Eight normal-weight women with PCOS and 8 age- and body mass index-matched controls. INTERVENTION(S): Women underwent circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S): PPARγ and CEBPa gene expression and lipid content of adipocytes matured in vitro were compared between women with PCOS and control women, and correlated with patient characteristics, systemic Si, and adipose insulin resistance (adipose-IR). RESULT(S): Serum androgen levels, adipose-IR, and percentage of android fat were greater in women with PCOS than control women. Stem cell PPARγ and CEBPa gene expression increased maximally by day 12 without a female-type effect. In control cells, gene expression positively correlated with fasting serum insulin levels (both genes) and adipose-IR (CEBPa) and negatively correlated with Si (CEBPa). Conversely, CEBPa gene expression in PCOS cells negatively correlated with adipose-IR and serum free testosterone, whereas total lipid accumulation in these cells positively corelated with Si. CONCLUSION: In normal-weight women with PCOS, accelerated SC abdominal adipose stem cell differentiation into adipocytes in vitro favors Si in vivo, suggesting a role for hyperandrogenism in the evolution of metabolic thrift to enhance fat storage through increased cellular glucose uptake.


Assuntos
Gordura Abdominal/metabolismo , Adipócitos/metabolismo , Adipogenia , Hiperandrogenismo/metabolismo , Resistência à Insulina , Síndrome do Ovário Policístico/metabolismo , Células-Tronco/metabolismo , Gordura Abdominal/patologia , Gordura Abdominal/fisiopatologia , Adipócitos/patologia , Adiposidade , Adulto , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Hiperandrogenismo/patologia , Hiperandrogenismo/fisiopatologia , Peso Corporal Ideal , Metabolismo dos Lipídeos , PPAR gama/genética , PPAR gama/metabolismo , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologia , Estudos Prospectivos , Células-Tronco/patologia , Fatores de Tempo , Adulto Jovem
13.
PLoS One ; 15(9): e0237496, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881912

RESUMO

BACKGROUND: Obesity is often associated with inflammation in adipose tissue (AT) with release of mediators of atherogenesis. We postulated that it would be feasible to collect sufficient abdominal AT to quantify changes in a broad array of adaptive and innate mononuclear white cells in obese non-diabetic adults in response to a dipeptidyl protease inhibitor (DPP4i), known to inhibit activation of immune white cells. METHODS: Adults 18-55 years-of-age were screened for abdominal obesity and insulin resistance or impaired glucose tolerance but without known inflammatory conditions. Twenty-one eligible participants consented for study and were randomized 3:1 to receive sitagliptin (DPP4i) at 100mg or matching placebo daily for 28 days. Abdominal AT collected by percutaneous biopsy and peripheral blood mononuclear cell fractions were evaluated before and after treatment; plasma was stored for batch testing. RESULTS: Highly sensitive C-reactive protein, a global marker of inflammation, was not elevated in the study population. Innate lymphoid cells (ILC) type 3 (ILC-3) in abdominal AT decreased with active treatment compared with placebo (p = 0.04). Other immune white cells in AT and peripheral blood mononuclear cell (PBMC) fractions did not change with treatment compared to placebo (p>0.05); although ILC-2 declined in PBMCs (p = 0.007) in the sitagliptin treatment group. Two circulating biomarkers of atherogenesis, interferon-inducible protein-10 (IP-10) and sCD40L declined in plasma (p = 0.02 and p = 0.07, respectively) in the active treatment group, providing indirect validation of a net reduction in inflammation. CONCLUSIONS: In this pilot study, two cell types of the innate lymphoid system, ILC-3 in AT and ILC-2 PBMCs declined during treatment and as did circulating biomarkers of atherogenesis. Changes in other immune cells were not demonstrable. The study showed that sufficient abdominal AT could be obtained to quantify white cells of both innate and adaptive immunity and to demonstrate changes during therapy with an immune inhibitor. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT02576.


Assuntos
Gordura Abdominal/patologia , Imunidade Inata , Leucócitos Mononucleares/patologia , Obesidade/imunologia , Adulto , Biomarcadores/sangue , Estudos de Viabilidade , Feminino , Citometria de Fluxo , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fosfato de Sitagliptina/farmacologia , Resultado do Tratamento
14.
Clin Exp Nephrol ; 24(10): 935-945, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32613494

RESUMO

BACKGROUND: Obesity is a risk factor for chronic kidney disease. Although body mass index (BMI) or waist circumference is indicators of obesity, actual measurements of visceral fat area (VFA) more accurately reflect the amount of visceral fat. We aimed to determine the most sensitive obesity indicator for predicting renal impairment among VFA, BMI, waist circumference, waist-to-height ratio, and visceral-to-subcutaneous fat ratio (VSR). METHODS: Subjects who underwent VFA measurements during health checkups in 2012 were included. Obesity was defined using a separate baseline value for each indicator [VFA (100 cm2), BMI (25 kg/m2), waist circumference (85 cm for men and 90 cm for women), waist-to-height ratio (0.5), VSR (0.4)]. Changes in estimated glomerular filtration rate (eGFRcr) and time to new-onset proteinuria were measured. The relationships between obesity indicators and eGFRcr were evaluated using a linear mixed-effects model. The relationships between obesity indicators and new-onset proteinuria were evaluated using Poisson regression analysis. RESULTS: Analysis was performed on 2753 subjects (mean age 50.3 years). The VFA ≥ 100 cm2 group exhibited a larger annual difference in eGFRcr compared to the < 100 cm2 group (- 0.24 mL/min/1.73 m2, P = 0.03). There was a statistically significant difference in the proteinuria incidence rate ratio, which was 1.54 times (95% confidence interval 1.01-2.35) in the VFA ≥ 100 cm2 group. Statistically significant correlations were not observed with any of the other obesity indicators. CONCLUSION: VFA is suggested to be the most sensitive obesity indicator for decline in kidney function and new-onset proteinuria.


Assuntos
Gordura Abdominal/patologia , Nefropatias/epidemiologia , Obesidade Abdominal/epidemiologia , Proteinúria/epidemiologia , Adulto , Estatura , Índice de Massa Corporal , Impedância Elétrica , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pletismografia de Impedância , Estudos Retrospectivos , Gordura Subcutânea/patologia , Circunferência da Cintura
16.
Surgery ; 167(5): 876-882, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32151368

RESUMO

BACKGROUND: Weight loss is often encouraged or required before open ventral hernia repair. This study evaluates the impact of weight change on total, intra-abdominal, subcutaneous, and hernia volume. METHODS: Patients who underwent open ventral hernia repair from 2007 to 2018 with two preoperative computed tomography scans were identified. Scans were reviewed using 3D volumetric software. Demographics, operative characteristics, and outcomes were evaluated. The impact of weight change on intra-abdominal, subcutaneous, and hernia volume was assessed using Spearman's correlation coefficients and linear regression models. RESULTS: A total of 250 patients met the criteria with a mean defect area of 155.6 ± 155.4 cm2, subcutaneous volume of 6,800.0 ± 3,868.8 cm3, hernia volume of 915.7 ± 1,234.5 cm3, intra-abdominal volume equaling 4,250.2 ± 2,118.1 cm3, and time between computed tomography scans 13.9 ± 11.0 months. Weight change was associated with change in hernia, intra-abdominal, total, and subcutaneous volume (Spearman's correlation coefficients 0.17, 0.48, 0.51, 0.45, respectively, P ≤ 0.03 all values) and not associated in hernia length, width, or area (P ≥ 0.18 all values). A Δ5 kg was significantly associated with Δintra-abdominal volume (164.1 ± 30.0 cm3/Δ5 kg,P < .0001), Δtotal volume (209.9 ± 33.0 cm3/Δ5 kg, P < .0001), and Δsubcutaneous volume (234.4 ± 50.8 cm3/Δ5 kg, P < .0001). Per Δ5 kg, male patients had more than double the Δintra-abdominal, Δtotal, and Δsubcutaneous volume than did female patients. A weight change of 5 kg to10 kg was associated with approximately double the change in computed tomography parameters/Δ5 kg than any weight change after 10 kg. Regardless of weight change, all measured hernia parameters increased over time, with mean hernia volume of +40.6 ± 94.9 cm3/mo and area of +7.8 ± 13.3 cm2/mo (Spearman's correlation coefficient -0.03 to 0.07, P value 0.37-0.96). CONCLUSION: Weight change is linearly correlated with intra-abdominal and subcutaneous fat gain or loss. Males show greater abdominal-related response to weight gain or loss. Hernia dimensions increase over time regardless of weight change.


Assuntos
Peso Corporal , Hérnia Abdominal/epidemiologia , Hérnia Abdominal/etiologia , Gordura Abdominal/patologia , Idoso , Feminino , Hérnia Abdominal/diagnóstico , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Tomografia Computadorizada por Raios X
17.
Diabetes Metab Syndr ; 14(6): 2185-2189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33395779

RESUMO

BACKGROUND AND AIM: Fat reduction and body contouring have become popular procedures in the cosmetic surgery industry over the past decade. There have been studies to replace invasive methods such as liposuction, with safer non-invasive procedures. We aimed to evaluate the effect of a non-invasive combination therapy of ultrasound cavitation and cryolipolysis on abdominal adipose tissue. METHODS: This pilot interventional study comprised 90 female individuals aged 18-65-years-old who were recruited into one of three groups of 30 participants. Group 1 was treated with diet alone (the control group), group 2 with cryolipolysis and diet, and group 3 with a combination of ultrasound cavitation, cryolipolysis, and diet for 8 weeks. Anthropometric parameters were measured before, during, and after the trial included total body weight, body mass index(BMI), body fat mass, fat-free mass, and abdomen circumference. RESULTS: All three groups demonstrated significant reductions in each parameter at the end of the intervention (P < 0.01). Apart from fat-free mass (P = 0.66), the combination therapy significantly reduced body fat mass, weight, BMI, and abdomen circumference compared to the control group (P < 0.01). There was no significant difference between the combination therapy and cryolipolysis-alone groups. CONCLUSION: Treatment using a combination of cryolipolysis and ultrasound cavitation is no more effective in improving the anthropometric indices than cryolipolysis alone.


Assuntos
Gordura Abdominal/cirurgia , Criocirurgia/métodos , Lipectomia/métodos , Obesidade/terapia , Terapia por Ultrassom/métodos , Gordura Abdominal/patologia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Adulto Jovem
18.
J Minim Invasive Gynecol ; 27(6): 1377-1382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31676398

RESUMO

STUDY OBJECTIVE: To evaluate whether obesity is a marker of surgical difficulty during extraperitoneal para-aortic lymphadenectomy. DESIGN: Retrospective observational cohort study. SETTING: Tertiary medical center in the Kanazawa area of Japan. PATIENTS: Eighty-four patients with primary endometrial cancer who underwent extraperitoneal laparoscopic para-aortic lymphadenectomy (LPAND) between January 2005 and December 2017 were included. INTERVENTIONS: We investigated the correlation between operative times and body mass indexes, visceral fat areas, and periabdominal artery fat areas (PAFAs). The number of lymph nodes harvested was used as an indicator of the degree of surgical completion. MEASUREMENTS AND MAIN RESULTS: There was no correlation between the operative time and body mass index. Significant correlations were observed between operative time and visceral fat area (p = .026; r = 0.243) and between operative time and PAFA (p = .007; r = 0.293). A multivariate analysis showed that PAFA was a significant independent marker that could be used to predict prolonged operative times for extraperitoneal LPAND (p = .045; odds ratio, 3.05). The number of para-aortic lymph nodes harvested was not significant in the high- and low-PAFA groups (22 and 25, respectively; p = .525). CONCLUSION: PAFA is an adequate marker of prolonged operative time for extraperitoneal LPAND among patients with endometrial cancer.


Assuntos
Gordura Abdominal/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Complicações Intraoperatórias/diagnóstico , Excisão de Linfonodo/efeitos adversos , Gordura Abdominal/diagnóstico por imagem , Adulto , Idoso , Aorta/diagnóstico por imagem , Aorta/patologia , Índice de Massa Corporal , Estudos de Coortes , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Japão/epidemiologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Duração da Cirurgia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
19.
Obes Surg ; 30(2): 401-406, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31713150

RESUMO

BACKGROUND: Most bariatric treatments employ gastric volume reduction. However, there has been no appropriate tool that could assess the anatomical factors of the stomach, and few studies have investigated proper stomach measurement for bariatric treatment. Thus, this study aimed to objectively estimate the individual stomach using three-dimensional (3D) computed tomography (CT) gastrography for the possible acquisition of information that could facilitate bariatric treatment and to validate these factors. METHODS: A total of 100 consecutive patients with different degrees of obesity who underwent 3D CT gastrography were enrolled. Using semiautomatic and manual segmentation tools, 3D volume-rendered images were constructed, and the total volume of the distended stomach, abdominal diameter, and abdominal fat volume (visceral and subcutaneous fat) were measured. Data on patients' baseline characteristics and laboratory findings were collected. RESULTS: The stomach volume measured using 3D CT gastrography ranged from 268 to 751 mL, whereas the stomach capacity was 572 ± 301.6 mL and 438.5 ± 163.4 mL in patients with body mass index (BMI) ≥ 25 kg/m2 and < 25 kg/m2, respectively. Visceral fat volume, abdominal circumference, and visceral-to-subcutaneous fat ratio tended to be associated with increased stomach volume. Multivariate analysis showed that BMI and visceral fat volume were significantly associated with stomach volume in female patients. CONCLUSIONS: The results of this study indicated the association of stomach volume with obesity status. Objective estimation of the individual stomach presented the possibility of tailored therapeutic approach to obese patients requiring more effective bariatric treatment.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/cirurgia , Estômago/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Gordura Abdominal/diagnóstico por imagem , Gordura Abdominal/patologia , Adulto , Idoso , Índice de Massa Corporal , Técnicas de Diagnóstico do Sistema Digestório , Feminino , Humanos , Imageamento Tridimensional , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Tamanho do Órgão , Cuidados Pré-Operatórios/métodos , Período Pré-Operatório , Estudos Prospectivos , Estômago/patologia
20.
Nutrients ; 11(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284400

RESUMO

This study evaluates the progressive participation of enzymes involved in lipolysis and lipogenesis, leading to adipocyte hypertrophy in a metabolic syndrome (MS) rat model caused by chronic consumption of 30% sucrose in drinking water. A total of 70 male Wistar rats were divided into two groups: C and MS. Each of these groups were then subdivided into five groups which were sacrificed as paired groups every month from the beginning of the treatment until 5 months. The intra-abdominal fat was dissected, and the adipocytes were extracted. Lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), protein kinases A (PKA), and perilipin A expressions were determined. The LPL and HSL activities were evaluated by spectrophotometry. Histological staining was performed in adipose tissue. Significant increases were observed in blood pressure, HOMA-IR, leptin, triglycerides, insulin, intra-abdominal fat, and number of fat cells per field (p = 0.001) and in advanced glycosylation products, adipocyte area, LPL, HSL activities and/or expression (p ≤ 0.01) in the MS groups progressively from the third month onward. Lipogenesis and lipolysis were increased by LPL activity and HSL activity and/or expression. This was associated with hyperinsulinemia and release of non-esterified fatty acids causing a positive feedback loop that contributes to the development of adipocyte hypertrophy.


Assuntos
Gordura Abdominal/metabolismo , Lipogênese , Lipólise , Síndrome Metabólica/metabolismo , Gordura Abdominal/patologia , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Sacarose Alimentar , Modelos Animais de Doenças , Progressão da Doença , Ácidos Graxos não Esterificados/metabolismo , Retroalimentação Fisiológica , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Hipertrofia , Lipase Lipoproteica/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Perilipina-1/metabolismo , Ratos Wistar , Transdução de Sinais , Esterol Esterase/metabolismo , Fatores de Tempo
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