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1.
Medicine (Baltimore) ; 100(41): e27487, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731128

RESUMO

ABSTRACT: Fatty pancreas (FP) is characterized by pancreatic fat accumulation and the subsequent development of pancreatic and metabolic complications. However, FP has not been categorized in the manual for abdominal ultrasound in cancer screening and health check-ups in Japan, and the pathology of FP has not been fully elucidated.Nine hundred and nineteen people who underwent a medical check-up had the severity of their pancreatic fat accumulation categorized after transabdominal ultrasonographic examination. The relationships between FP, lifestyle-related diseases, and fatty liver disease at this time were assessed using stratification analysis.The prevalence of FP was 46.8% (430/919). People with FP were more likely to be male and had higher prevalences of lifestyle-related diseases, including fatty liver disease. Men and women were similarly represented in each tertile of pancreas brightness. Older age; high waist circumference, triglyceride and glucose index, serum low-density lipoprotein-cholesterol, hepatic steatosis index; and low serum amylase were associated with the presence of severe FP. Moreover, the group with severe liver steatosis had a higher prevalence of FP and a higher pancreatic brightness score. Logistic regression analysis showed that individuals with liver steatosis were more likely to have severe FP.The severity of FP is associated with features of lifestyle-related diseases and the severity of liver steatosis. These findings suggest that high visceral fat content is associated with more severe fatty pancreas as a phenotype of ectopic fat accumulation, as well as fatty liver disease.


Assuntos
Gordura Intra-Abdominal/patologia , Pâncreas/patologia , Pancreatopatias/patologia , Exame Físico/normas , Adulto , Idoso , Amilases/sangue , Glicemia , LDL-Colesterol/sangue , Estudos Transversais , Fígado Gorduroso/epidemiologia , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Japão/epidemiologia , Estilo de Vida , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/etiologia , Pessoa de Meia-Idade , Pancreatopatias/complicações , Pancreatopatias/epidemiologia , Fenótipo , Prevalência , Índice de Gravidade de Doença , Triglicerídeos/sangue , Ultrassonografia/métodos , Circunferência da Cintura
2.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638880

RESUMO

Development and severity of nonalcoholic fatty liver disease (NAFLD) have been linked to obesity and white adipose tissue (WAT) dysfunction plays a key role in this relation. We compared the main features of subcutaneous (SAT) and visceral WAT (VAT) tissue dysfunction in 48 obese women without (Ob) and with NAFLD (Ob-NAFLD) undergoing bariatric surgery and matched for age, BMI and T2D status. Fat cell area, adipocyte size distribution, the degree of histological fibrosis and the mRNA expression of adipokines and genes implicated in inflammation, adipogenesis, angiogenesis, metabolism and extracellular matrix remodeling were measured by RT-qPCR in both fat depots. Ob-NAFLD group showed higher TG and lower HDL circulating levels, increased VAT fat cell area and similar WAT fibrosis in comparison with Ob group. A sPLS-DA was performed in order to identify the set of genes that better characterize the presence of NAFLD. Finally, we build a multinomial logistic model including seven genes that explained 100% of the variance in NAFLD and correctly predicted 100% of cases. Our data support the existence of distinctive NAFLD signatures in WAT from women with severe obesity. A better understanding of these pathways may help in future strategies for the prevention and treatment of NAFLD.


Assuntos
Adipocinas/biossíntese , Regulação da Expressão Gênica , Gordura Intra-Abdominal/metabolismo , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Mórbida/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/patologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Gordura Subcutânea/patologia
3.
Life Sci ; 285: 119997, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34597608

RESUMO

AIM: Sirtuin 2 (SIRT2) is a NAD+-dependent deacetylase involved in various biological functions via deacetylation of proteins, including histone protein. Hepatic fat accumulation from aging and excess caloric intake contribute to development of non-alcoholic fatty liver disease. The study aim was to elucidate the role of SIRT2 in lipid metabolism homeostasis. MATERIALS AND METHODS: SIRT2+/+ (C57BL/6) and SIRT2-/- were randomly assigned to normal diet or high-fat diet (HFD) groups and fed for 6 weeks. Histological features of the livers were evaluated by hematoxylin and eosin and Masson's trichrome staining, and the levels of selected factors were determined by quantitative reverse transcription-polymerase chain reaction and western blot analysis. KEY FINDINGS: Although the SIRT2-/- mice were viable, their livers exhibited higher glycogen accumulation, and skeletal muscle showed features of increased metabolic demand. The SIRT2-/- mice attenuated HFD-induced weight gain, visceral adipose tissue formation, and fat accumulation in the liver in which the expressions of genes involved in metabolic substrate transport were modified. Additionally, the hepatocellular senescence and upregulated cell-cycle factors upon HFD intake in SIRT2-/- livers suggested a role of SIRT2 in gene expression during abnormal metabolism. Moreover, the fibrotic phenotype of liver tissue without fat accumulation and the increased expression of genes involved in liver fibrosis in the HFD-fed SIRT2-/- mice indicated that SIRT2 had a role in hepatocyte and hepatic stellate cell activation. SIGNIFICANCE: Our results indicated that SIRT2 has a critical role in regulating lipid metabolic homeostasis and in sustaining liver integrity by modulating related gene expression.


Assuntos
Gorduras/metabolismo , Cirrose Hepática/metabolismo , Sirtuína 2/fisiologia , Animais , Senescência Celular , Dieta Hiperlipídica , Glicogênio/metabolismo , Homeostase , Gordura Intra-Abdominal/metabolismo , Fígado/citologia , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sirtuína 2/genética , Ganho de Peso/genética
4.
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
5.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502056

RESUMO

Skeletal tissue involves systemic adipose tissue metabolism and energy expenditure. MicroRNA signaling controls high-fat diet (HFD)-induced bone and fat homeostasis dysregulation remains uncertain. This study revealed that transgenic overexpression of miR-29a under control of osteocalcin promoter in osteoblasts (miR-29aTg) attenuated HFD-mediated body overweight, hyperglycemia, and hypercholesterolemia. HFD-fed miR-29aTg mice showed less bone mass loss, fatty marrow, and visceral fat mass together with increased subscapular brown fat mass than HFD-fed wild-type mice. HFD-induced O2 underconsumption, respiratory quotient repression, and heat underproduction were attenuated in miR-29aTg mice. In vitro, miR-29a overexpression repressed transcriptomic landscapes of the adipocytokine signaling pathway, fatty acid metabolism, and lipid transport, etc., of bone marrow mesenchymal progenitor cells. Forced miR-29a expression promoted osteogenic differentiation but inhibited adipocyte formation. miR-29a signaling promoted brown/beige adipocyte markers Ucp-1, Pgc-1α, P2rx5, and Pat2 expression and inhibited white adipocyte markers Tcf21 and Hoxc9 expression. The microRNA also reduced peroxisome formation and leptin expression during adipocyte formation and downregulated HFD-induced leptin expression in bone tissue. Taken together, miR-29a controlled leptin signaling and brown/beige adipocyte formation of osteogenic progenitor cells to preserve bone anabolism, which reversed HFD-induced energy underutilization and visceral fat overproduction. This study sheds light on a new molecular mechanism by which bone integrity counteracts HFD-induced whole-body fat overproduction.


Assuntos
Gordura Intra-Abdominal/metabolismo , Leptina/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoporose/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Leptina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Osteoblastos/citologia , Osteoporose/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Peroxissomos/metabolismo , Receptores Purinérgicos P2X5/genética , Receptores Purinérgicos P2X5/metabolismo , Simportadores/genética , Simportadores/metabolismo , Termogênese , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
6.
Nutrients ; 13(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34578784

RESUMO

Background: Epicardial adipose tissue (EAT) is a visceral fat depot with unique anatomic, biomolecular and genetic features. Due to its proximity to the coronary arteries and myocardium, dysfunctional EAT may contribute to the development and progression of cardiovascular and metabolic-related adiposity-based chronic diseases. The aim of this work was to describe, by morphological techniques, the early origin of EAT. Methods: EAT adipogenesis was studied in 41 embryos from 32 gestational days (GD) to 8 gestational weeks (GW) and in 23 fetuses until full term (from 9 to 36 GW). Results: This process comprises five stages. Stage 1 appears as mesenchyme at 33-35 GD. Stage 2 is characterized by angiogenesis at 42-45 GD. Stage 3 covers up to 34 GW with the appearance of small fibers in the extracellular matrix. Stage 4 is visible around the coronary arteries, as multilocular adipocytes in primitive fat lobules, and Stage 5 is present with unilocular adipocytes in the definitive fat lobules. EAT precursor tissue appears as early as the end of the first gestational month in the atrioventricular grooves. Unilocular adipocytes appear at the eighth gestational month. Conclusions: Due to its early origin, plasticity and clinical implications, factors such as maternal health and nutrition might influence EAT early development in consequence.


Assuntos
Tecido Adiposo/patologia , Doenças Cardiovasculares/epidemiologia , Desenvolvimento Fetal , Obesidade/epidemiologia , Pericárdio/patologia , Adipócitos/metabolismo , Adipogenia , Tecido Adiposo/metabolismo , Vasos Coronários/patologia , Feminino , Feto/patologia , Idade Gestacional , Humanos , Gordura Intra-Abdominal/metabolismo , Miocárdio/patologia , Pericárdio/metabolismo , Gravidez
7.
Nutrients ; 13(9)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34579170

RESUMO

This study aimed to investigate relationships between infant abdominal visceral and subcutaneous adiposity and human milk (HM) components and maternal body composition (BC) during first year of lactation. Subcutaneous-abdominal depth (SAD), subcutaneous-abdominal fat area (SFA), visceral depth (VD) and preperitoneal fat area of 20 breastfed infants were assessed at 2, 5, 9 and 12 months using ultrasound. Maternal BC was determined with bioimpedance spectroscopy. HM macronutrients and bioactive components concentrations and infant 24-h milk intake were measured and calculated daily intakes (CDI) determined. Maternal adiposity associated with infant SFA (negatively at 2, 5, 12, positively at 9 months, all overall p < 0.05). 24-h milk intake positively associated with infant SAD (p = 0.007) and VD (p = 0.013). CDI of total protein (p = 0.013), total carbohydrates (p = 0.004) and lactose (p = 0.013) positively associated with SFA. Lactoferrin concentration associated with infant VD (negatively at 2, 12, positively at 5, 9 months, overall p = 0.003). CDI of HM components and maternal adiposity have differential effects on development of infant visceral and subcutaneous abdominal adiposity. Maintaining healthy maternal BC and continuing breastfeeding to 12 months and beyond may facilitate favourable BC development reducing risk of obesity.


Assuntos
Composição Corporal , Aleitamento Materno/métodos , Gordura Intra-Abdominal/metabolismo , Leite Humano/química , Gordura Subcutânea Abdominal/metabolismo , Adiponectina/análise , Adiposidade , Peso Corporal , Carboidratos da Dieta/análise , Feminino , Humanos , Lactente , Lactação/metabolismo , Leptina/análise , Estudos Longitudinais , Masculino , Nutrientes/análise , Obesidade/epidemiologia
8.
Nutrients ; 13(8)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34444654

RESUMO

Visceral adipose tissue (VAT) accumulation, is a part of a polycystic ovary syndrome (PCOS) phenotype. Dual-energy x-ray absorptiometry (DXA) provides a gold standard measurement of VAT. This study aimed to compare ten different indirect methods of VAT estimation in PCOS women. The study included 154 PCOS and 68 age- and BMI-matched control women. Subjects were divided into age groups: 18-30 y.o. and 30-40 y.o. Analysis included: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist/height 0.5 (WHT.5R), visceral adipose index (VAI), lipid accumulation product (LAP), and fat mass index (FMI). VAT accumulation, android-to-gynoid ratio (A/G), and total body fat (TBF) was measured by DXA. ROC analysis revealed that WHtR, WHT.5R, WC, BMI, and LAP demonstrated the highest predictive value in identifying VAT in the PCOS group. Lower cut-off values of BMI (23.43 kg/m2) and WHtR (0.45) were determined in the younger PCOS group and higher thresholds of WHtR (0.52) in the older PCOS group than commonly used. Measuring either: WHtR, WHT.5R, WC, BMI, or LAP, could help identify a subgroup of PCOS patients at high cardiometabolic risk. The current observations reinforce the importance of using special cut-offs to identify VAT, dependent on age and PCOS presence.


Assuntos
Absorciometria de Fóton , Adiposidade , Antropometria , Gordura Intra-Abdominal/fisiopatologia , Síndrome do Ovário Policístico/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
9.
Eur J Endocrinol ; 185(5): 653-662, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34406976

RESUMO

Objective: Increased visceral fat and sarcopenia are cardiovascular risk factors that may explain increased cardiovascular morbidity and frailty in patients with adrenal adenomas. Our objective was to compare body composition measurement of patients with adrenal adenomas to referent subjects without adrenal disease. Design: Cross-sectional study, 2014-2018. Methods: Participants were adults with nonfunctioning adrenal tumor (NFAT), mild autonomous cortisol secretion (MACS), and Cushing syndrome (CS) and age, sex, and BMI 1:1 matched referent subjects without adrenal disorders. Main outcome measures were body composition measurements calculated from abdominal CT imaging. Intra-abdominal adipose tissue and muscle mass measurements were performed at the third lumbar spine level. Results: Of 227 patients with adrenal adenomas, 20 were diagnosed with CS, 76 with MACS, and 131 with NFAT. Median age was 56 years (range: 18-89), and 67% were women. When compared to referent subjects, patients with CS, MACS, and NFAT demonstrated a higher visceral fat (odds ratio (OR): 2.2 (95% CI: 0.9-6.5), 2.0 (1.3-3.2), and 1.8 (1.2-2.7) and a lower skeletal muscle area (OR: 0.01 (95% CI: 0-0.09), 0.31 (0.18-0.49), and 0.3 (1.2-2.7)) respectively. For every 1 µg/dL cortisol increase after overnight dexamethasone, visceral fat/muscle area ratio increased by 2.3 (P = 0.02) and mean total skeletal muscle area decreased by 2.2 cm2 (P = 0.03). Conclusion: Patients with adrenal adenomas demonstrate a lower muscle mass and a higher proportion of visceral fat when compared to referent subjects, including patients with NFAT. Even a subtle abnormality in cortisol secretion may impact health of patients with adenomas.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/metabolismo , Composição Corporal , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/metabolismo , Adolescente , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Adenoma Adrenocortical/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Síndrome de Cushing/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Estudos Prospectivos , Sarcopenia/metabolismo , Gordura Subcutânea/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
10.
Sci Rep ; 11(1): 17394, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462518

RESUMO

Dysfunctional visceral adipose tissue (VAT) in obesity is associated with type 2 diabetes (DM) but underlying mechanisms remain unclear. Our objective in this discovery analysis was to identify genes and proteins regulated by DM to elucidate aberrant cellular metabolic and signaling mediators. We performed label-free proteomics and RNA-sequencing analysis of VAT from female bariatric surgery subjects with DM and without DM (NDM). We quantified 1965 protein groups, 23 proteins, and 372 genes that were differently abundant in DM vs. NDM VAT. Proteins downregulated in DM were related to fatty acid synthesis and mitochondrial function (fatty acid synthase, FASN; dihydrolipoyl dehydrogenase, mitochondrial, E3 component, DLD; succinate dehydrogenase-α, SDHA) while proteins upregulated in DM were associated with innate immunity and transcriptional regulation (vitronectin, VTN; endothelial protein C receptor, EPCR; signal transducer and activator of transcription 5B, STAT5B). Transcriptome indicated defects in innate inflammation, lipid metabolism, and extracellular matrix (ECM) function, and components of complement classical and alternative cascades. The VAT proteome and transcriptome shared 13 biological processes impacted by DM, related to complement activation, cell proliferation and migration, ECM organization, lipid metabolism, and gluconeogenesis. Our data revealed a marked effect of DM in downregulating FASN. We also demonstrate enrichment of complement factor B (CFB), coagulation factor XIII A chain (F13A1), thrombospondin 1 (THBS1), and integrins at mRNA and protein levels, albeit with lower q-values and lack of Western blot or PCR confirmation. Our findings suggest putative mechanisms of VAT dysfunction in DM.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Gordura Intra-Abdominal/metabolismo , Obesidade/patologia , Proteoma/metabolismo , Transcriptoma , Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/complicações , Regulação para Baixo , Matriz Extracelular/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Mitocôndrias/genética , Obesidade/complicações , Análise de Componente Principal , Regulação para Cima
11.
Sci Rep ; 11(1): 17050, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426590

RESUMO

The study of metabolomics has improved our knowledge of the biology behind type 2 diabetes and its related metabolic physiology. We aimed to investigate markers of adipose tissue morphology, as well as insulin and glucose metabolism in 53 non-obese male individuals. The participants underwent extensive clinical, biochemical and magnetic resonance imaging phenotyping, and we also investigated non-targeted serum metabolites. We used a multi-modal machine learning approach to evaluate which serum metabolomic compounds predicted markers of glucose and insulin metabolism, adipose tissue morphology and distribution. Fasting glucose was associated with metabolites of intracellular insulin action and beta-cell dysfunction, namely cysteine-s-sulphate and n-acetylgarginine, whereas fasting insulin was predicted by myristoleoylcarnitine, propionylcarnitine and other metabolites of beta-oxidation of fatty acids. OGTT-glucose levels at 30 min were predicted by 7-Hoca, a microbiota derived metabolite, as well as eugenol, a fatty acid. Both insulin clamp and HOMA-IR were predicted by metabolites involved in beta-oxidation of fatty acids and biodegradation of triacylglycerol, namely tartrate and 3-phosphoglycerate, as well as pyruvate, xanthine and liver fat. OGTT glucose area under curve (AUC) and OGTT insulin AUC, was associated with bile acid metabolites, subcutaneous adipocyte cell size, liver fat and fatty chain acids and derivates, such as isovalerylcarnitine. Finally, subcutaneous adipocyte size was associated with long chain fatty acids, markers of sphingolipid metabolism, increasing liver fat and dopamine-sulfate 1. Ectopic liver fat was predicted by methylmalonate, adipocyte cell size, glutathione derived metabolites and fatty chain acids. Ectopic heart fat was predicted visceral fat, gamma-glutamyl tyrosine and 2-acetamidophenol sulfate. Adipocyte cell size, age, alpha-tocopherol and blood pressure were associated with visceral fat. We identified several biomarkers associated with adipose tissue pathophysiology and insulin and glucose metabolism using a multi-modal machine learning approach. Our approach demonstrated the relative importance of serum metabolites and they outperformed traditional clinical and biochemical variables for most endpoints.


Assuntos
Adiposidade , Glicemia/metabolismo , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Biomarcadores/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Gordura Intra-Abdominal/citologia , Fígado/metabolismo , Aprendizado de Máquina , Masculino , Metaboloma , Pessoa de Meia-Idade , Gordura Subcutânea/citologia
12.
Acta Psychiatr Scand ; 144(6): 524-536, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34458979

RESUMO

OBJECTIVE: Although a relationship between schizophrenia (SCZ), antipsychotic (AP) medication, and metabolic dysregulation is now well established, the effect of adiposity is less well understood. By synthesizing findings from imaging techniques that measure adiposity, our systematic review and meta-analysis (PROSPERO CRD42020192977) aims to determine the adiposity-related effects of illness and treatment in this patient population. METHODS: We searched MEDLINE, EMBASE, PsychINFO and Scopus for all relevant case-control and prospective longitudinal studies from inception until February 2021. Measures of adiposity including percent body fat (%BF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were analyzed as primary outcomes. RESULTS: Our search identified 29 articles that used imaging methods to quantify adiposity among patients with SCZ spectrum disorders. Analyses revealed that patients have greater %BF (mean difference (MD) = 3.09%; 95% CI: 0.75-5.44), SAT (MD = 24.29 cm2 ; 95% CI: 2.97-45.61) and VAT (MD = 33.73 cm2 , 95% CI: 4.19-63.27) compared to healthy controls. AP treatment was found to increase SAT (MD = 31.98 cm2 ; 95% CI: 11.33-52.64) and VAT (MD = 16.30 cm2 ; 95% CI: 8.17-24.44) with no effect on %BF. However, change in %BF was higher for AP-free/AP-naïve patients compared to treated patients. CONCLUSION: Our findings indicate that patients with SCZ spectrum disorders have greater adiposity than healthy controls, which is increased by AP treatment. Young, AP-naïve patients may be particularly susceptible to this effect. Future studies should explore the effect of specific APs on adiposity and its relation to overall metabolic health.


Assuntos
Adiposidade , Esquizofrenia , Humanos , Gordura Intra-Abdominal/metabolismo , Obesidade , Estudos Prospectivos , Esquizofrenia/metabolismo , Gordura Subcutânea/metabolismo
13.
Biochem Pharmacol ; 192: 114723, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34364887

RESUMO

Both obesity and aging are associated with the development of metabolic diseases such as type 2 diabetes and cardiovascular disease. Chronic low-grade inflammation of adipose tissue is one of the mechanisms implicated in the progression of these diseases. Obesity and aging trigger adipose tissue alterations that ultimately lead to a pro-inflammatory phenotype of the adipose tissue-resident immune cells. Obesity and aging also share other features such as a higher visceral vs. subcutaneous adipose tissue ratio and a decreased lifespan. Here, we review the common characteristics of obesity and aging and the alterations in white adipose tissue and resident immune cells. We focus on the adipose tissue metabolic derangements in obesity and aging such as inflammation and adipose tissue remodeling.


Assuntos
Adipócitos Brancos/imunologia , Tecido Adiposo Branco/imunologia , Envelhecimento/imunologia , Distribuição da Gordura Corporal/métodos , Obesidade/imunologia , Adipócitos Brancos/metabolismo , Adipócitos Brancos/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Humanos , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Obesidade/metabolismo , Obesidade/patologia
14.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299331

RESUMO

BACKGROUND: Due to its prominence in the regulation of metabolism and inflammation, adipose tissue is a major target to investigate alterations in insulin action. This hormone activates PI3K/AKT pathway which is essential for glucose homeostasis, cell differentiation, and proliferation in insulin-sensitive tissues, like adipose tissue. The aim of this work was to evaluate the impact of chronic and intermittent high glucose on the expression of biomolecules of insulin signaling pathway during the differentiation and maturation of human visceral preadipocytes. METHODS: Human visceral preadipocytes (HPA-V) cells were treated with high glucose (30 mM)during the proliferation and/or differentiation and/or maturation stage. The level of mRNA (by Real-Time PCR) and protein (by Elisa tests) expression of IRS1, PI3K, PTEN, AKT2, and GLUT4 was examined after each culture stage. Furthermore, we investigated whether miR-29a-3p, miR-143-3p, miR-152-3p, miR-186-5p, miR-370-3p, and miR-374b-5p may affect the expression of biomolecules of the insulin signaling pathway. RESULTS: Both chronic and intermittent hyperglycemia affects insulin signaling in visceral pre/adipocytes by upregulation of analyzed PI3K/AKT pathway molecules. Both mRNA and protein expression level is more dependent on stage-specific events than the length of the period of high glucose exposure. What is more, miRs expression changes seem to be involved in PI3K/AKT expression regulation in response to hyperglycemic stimulation.


Assuntos
Hiperglicemia/metabolismo , Gordura Intra-Abdominal/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Expressão Gênica , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Humanos , Hiperglicemia/patologia , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais
15.
Life Sci ; 283: 119841, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34298036

RESUMO

Sympathetic vasomotor overactivity is a major feature leading to the cardiovascular dysfunction related to obesity. Considering that the retroperitoneal white adipose tissue (rWAT) is an important fat visceral depot and receives intense sympathetic and afferent innervations, the present study aimed to evaluate the effects evoked by bilateral rWAT denervation in obese rats. Male Wistar rats were fed with HFD for 8 consecutive weeks and rWAT denervation was performed at the 6th week. Arterial pressure, splanchnic and renal sympathetic vasomotor nerve activities were assessed and inflammation and the components of the renin -angiotensin system were evaluated in different white adipose tissue depots. HFD animals presented higher serum levels of leptin and glucose, an increase in arterial pressure and splanchnic sympathetic nerve activity; rWAT denervation, normalized these parameters. Pro-inflammatory cytokines levels were significantly increased, as well as RAAS gene expression in WAT of HFD animals; rWAT denervation significantly attenuated these changes. In conclusion, HFD promotes vasomotor sympathetic overactivation and inflammation with repercussions on the cardiovascular system. In conclusion, the neural communication between WAT and the brain is fundamental to trigger sympathetic vasomotor activation and this pathway is a possible new therapeutic target to treat obesity-associated cardiovascular dysfunction.


Assuntos
Doenças Cardiovasculares , Denervação , Dieta Hiperlipídica/efeitos adversos , Gordura Intra-Abdominal , Obesidade , Nervos Esplâncnicos , Animais , Pressão Sanguínea , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Gordura Intra-Abdominal/inervação , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/fisiopatologia , Masculino , Obesidade/induzido quimicamente , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade/terapia , Ratos , Ratos Wistar , Sistema Renina-Angiotensina , Nervos Esplâncnicos/metabolismo , Nervos Esplâncnicos/patologia , Nervos Esplâncnicos/fisiopatologia
16.
Psychosom Med ; 83(8): 834-842, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34292207

RESUMO

OBJECTIVE: We investigated the role of chronic stress burden on adiposity and adiposity-related inflammation with two hypotheses: a) greater chronic stress is associated with higher central adiposity and selective accumulation of visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT), and b) associations between VAT and inflammatory biomarkers are exacerbated when chronic stress is high. METHODS: Data come from 1809 participants included in a Multi-Ethnic Study of Atherosclerosis ancillary study of body composition and adiposity-related inflammation. Chronic psychosocial stress was measured with a five-item version of the Chronic Stress Burden Scale. First, we tested associations between chronic stress (three-level categorical variable) and VAT, SAT, and VAT/SAT ratio. Second, we tested whether associations between VAT and inflammatory biomarkers varied by level of chronic stress. RESULTS: Participants were approximately 65 years, 50% female, and 40.5% White, 25.6% Hispanic, 21.2% African American, and 12.8% Chinese American. About half of the sample reported little to no stress, and a quarter and a fifth of the sample reported medium and high levels of stress. Higher levels of chronic stress were associated with greater VAT and SAT, but not VAT/SAT ratio. Greater levels of VAT were associated with increased levels of adiposity-related inflammation in a graded pattern. These associations did not vary by stress level. CONCLUSIONS: Greater chronic stress burden is associated with both central and subcutaneous adiposity. We found no evidence that the associations between VAT and inflammatory biomarkers are exacerbated by chronic stress. Findings contribute to ongoing literature untangling pathways in which psychosocial stress contributes to adiposity-related inflammation.


Assuntos
Aterosclerose , Gordura Intra-Abdominal , Tecido Adiposo , Adiposidade , Aterosclerose/etiologia , Índice de Massa Corporal , Feminino , Humanos , Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino
17.
Sci Rep ; 11(1): 14750, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285301

RESUMO

Menopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. In this cross-sectional study of 33 women between 45 and 60 years, we assessed adipose tissue inflammation and morphology in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) across menopause and related this to menopausal differences in adipose tissue distribution and insulin resistance. We collected paired SAT and VAT biopsies from all women and combined this with anthropometric measurements and estimated whole-body insulin sensitivity. We found that menopause was associated with changes in adipose tissue phenotype related to metabolic dysfunction. In SAT, postmenopausal women showed adipocyte hypertrophy, increased inflammation, hypoxia and fibrosis. The postmenopausal changes in SAT was associated with increased visceral fat accumulation. In VAT, menopause was associated with adipocyte hypertrophy, immune cell infiltration and fibrosis. The postmenopausal changes in VAT phenotype was associated with decreased insulin sensitivity. Based on these findings we suggest, that menopause is associated with changes in adipose tissue phenotype related to metabolic dysfunction in both SAT and VAT. Whereas increased SAT inflammation in the context of menopause is associated with VAT accumulation, VAT morphology is related to insulin resistance.


Assuntos
Gordura Intra-Abdominal/patologia , Gordura Subcutânea Abdominal/patologia , Envelhecimento , Distribuição da Gordura Corporal , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Inflamação/patologia , Insulina/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Menopausa , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Fenótipo , Gordura Subcutânea Abdominal/metabolismo
18.
Biochem Biophys Res Commun ; 569: 118-124, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34243067

RESUMO

The mammalian target of rapamycin complex 1 (mTORC1) is a crucial regulator of adipogenesis and systemic energy metabolism. Its dysregulation leads to a diversity of metabolic diseases, including obesity and type 2 diabetes. DEP-domain containing 5 (DEPDC5) is a critical component of GATOR1 complex that functions as a key inhibitor of mTORC1. So far, its function in adipose tissue remains largely unknown. Herein we evaluated how persistent mTORC1 activation in adipocyte via Depdc5 knockout modulates adiposity in vivo. Our data indicated that adipocyte-specific knockout of Depdc5 in aged mice led to reduced visceral fat, aggravated insulin resistance and enhanced adipose tissue inflammation. Moreover, we found that Depdc5 ablation resulted in upregulation of adipose triglyceride lipase (ATGL) in adipocytes and elevated levels of serum free fatty acids (FFAs). Intriguingly, rapamycin treatment did not reverse insulin resistance but alleviated adipose tissue inflammation caused by Depdc5 deletion. Taken together, our findings revealed that mTORC1 activation caused by Depdc5 deletion promotes lipolysis process and further exacerbates insulin resistance and adipose tissue inflammation in mice.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Proteínas Ativadoras de GTPase/genética , Inflamação/genética , Resistência à Insulina/genética , Adipogenia/genética , Tecido Adiposo/patologia , Fatores Etários , Animais , Western Blotting , Dieta Hiperlipídica/efeitos adversos , Proteínas Ativadoras de GTPase/deficiência , Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismo , Lipase/genética , Lipase/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Obesidade/etiologia , Obesidade/genética , Obesidade/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética
19.
Cells ; 10(6)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208471

RESUMO

TBC1D4 (AS160) and TBC1D1 are Rab GTPase-activating proteins that play a key role in the regulation of glucose and possibly the transport of long chain fatty acids (LCFAs) into muscle and fat cells. Knockdown (KD) of TBC1D4 increased CD36/SR-B2 and FABPpm protein expressions in L6 myotubes, whereas in murine cardiomyocytes, TBC1D4 deficiency led to a redistribution of CD36/SR-B2 to the sarcolemma. In our study, we investigated the previously unexplored role of both Rab-GAPs in LCFAs uptake in human adipocytes differentiated from the ADMSCs of subcutaneous and visceral adipose tissue origin. To this end we performed a single- and double-knockdown of the proteins (TBC1D1 and TBC1D4). Herein, we provide evidence that AS160 mediates fatty acid entry into the adipocytes derived from ADMSCs. TBC1D4 KD resulted in quite a few alterations to the cellular phenotype, the most obvious of which was the shift of the CD36/SR-B2 transport protein to the plasma membrane. The above translated into an increased uptake of saturated long-chain fatty acid. Interestingly, we observed a tissue-specific pattern, with more pronounced changes present in the adipocytes derived from subADMSCs. Altogether, our data show that in human adipocytes, TBC1D4, but not TBC1D1, deficiency increases LCFAs transport via CD36/SR-B2 translocation.


Assuntos
Adipócitos/metabolismo , Ácidos Graxos/metabolismo , Proteínas Ativadoras de GTPase/deficiência , Gordura Intra-Abdominal/metabolismo , Gordura Subcutânea/metabolismo , Antígenos CD36/metabolismo , Células Cultivadas , Feminino , Humanos , Glicoproteínas de Membrana Associadas ao Lisossomo/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Receptores Depuradores/metabolismo
20.
Front Immunol ; 12: 690069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322121

RESUMO

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPRdn , hIAPP and PNPLA3I148M . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8+ T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 2/imunologia , Gordura Intra-Abdominal/imunologia , Fígado/imunologia , Ativação Linfocitária , Hepatopatia Gordurosa não Alcoólica/imunologia , Precursor de Proteína beta-Amiloide/genética , Animais , Animais Geneticamente Modificados , Glicemia/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Lipase/genética , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores dos Hormônios Gastrointestinais/genética , Suínos/genética , Transcriptoma
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