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1.
PLoS One ; 19(2): e0298068, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38363727

RESUMO

This is a retrospective cross-sectional study examining the association between unemployment, cancer type, treatment and total body fat percentage of childhood cancer survivors recruited at St. Anne's University Hospital in Brno, Czech Republic. A total of 55 survivors aged 18-49 who were in remission of cancer and fulfilled the criteria for body composition measurements by the BIA and completed questionnaires investigating their socioeconomic status, employment status, and history. There was a significant relationship between the employment status and central nervous system-directed treatment (c2(1) = 7.53, p = 0.006, Cramér's V = 0.38) and between the type of cancer and employment status (c2(3) = 7.83, p = 0.049, Cramér's V = 0.38), the highest unemployment rate was recorded for brain and spine survivors (72.7%) compared to survivors with other diagnosis (35.7%) (uLR(1) = 4.91, p = 0.027; OR = 4.80, 95% CI:1.10-20.86, p = 0.036); these survivors did not have a significantly different body fat percentage compared to survivors with other diagnoses (t(53) = 1.29, p = 0.202, Cohen's d = 0.41) Interestingly, the survivors reporting having a partner also had a significantly higher percentage of body fat (t(53) = 2.90, p = 0.005, Cohen's d = 0.81). A linear regression model was used to model the percentage of body fat in relation to a set of selected variables and the we observed a significant effect of sex (female vs male: b = 6.37, 95% CI: 1.82-10.93, p = 0.007), partnership status (yes vs no: b = 5.65, 95% CI: 0.67-10.62, p = 0.027) and category of diagnosis (Brain and spinal column tumors vs Other solid tumors: b = 12.40, 95% CI: 0.59-24.21, p = 0.040; Brain and spinal column tumors vs Lymphoma: b = 14.02, 95% CI: 2.06-25.97, p = 0.023). Employment status and risk of adiposity in childhood cancer survivors depends on the type of treatment and diagnosis group, which may significantly impact their lifestyle and overall quality of life after treatment. Trial registration: This study was registered on July 29, 2022, at ClinicalTrials.gov (NCT05481229).


Assuntos
Sobreviventes de Câncer , Neoplasias do Sistema Nervoso Central , Neoplasias , Humanos , Masculino , Criança , Feminino , Estudos Retrospectivos , Estudos Transversais , Neoplasias/epidemiologia , Neoplasias/terapia , Adiposidade , Qualidade de Vida , Obesidade , Classe Social
2.
Am J Physiol Endocrinol Metab ; 325(5): E562-E580, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37792298

RESUMO

In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies.NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Obesidade Mórbida , Masculino , Feminino , Humanos , Obesidade Mórbida/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estudos Transversais , Proteômica , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Gordura Subcutânea/metabolismo , Biomarcadores/metabolismo , Proteínas/metabolismo , Gordura Intra-Abdominal/metabolismo
3.
J Clin Endocrinol Metab ; 107(3): 755-775, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-34669916

RESUMO

CONTEXT: Adipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities. OBJECTIVE: Here we aim to compare the proteomic profiles of mature adipocytes from different depots. METHODS: Abdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data. RESULTS: We identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. CONCLUSION: Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity.


Assuntos
Adipócitos/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade Mórbida/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adulto , Cirurgia Bariátrica , Feminino , Redes Reguladoras de Genes , Humanos , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/patologia , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Omento/citologia , Omento/metabolismo , Omento/patologia , Omento/cirurgia , Proteômica , Gordura Subcutânea Abdominal/citologia , Gordura Subcutânea Abdominal/patologia
4.
Pharmacol Rep ; 71(4): 669-675, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31195344

RESUMO

BACKGROUND: Neurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier. METHODS: Adult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid. RESULTS: A significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit. CONCLUSION: This study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated.


Assuntos
Barreira Hematoencefálica/metabolismo , Encefalopatias/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Fatores de Crescimento Neural/sangue , Administração Oral , Animais , Transporte Biológico , Barreira Hematoencefálica/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Modelos Animais de Doenças , Masculino , Fatores de Crescimento Neural/administração & dosagem , Fatores de Crescimento Neural/líquido cefalorraquidiano , Bulbo Olfatório/cirurgia , Estudo de Prova de Conceito , Ratos Sprague-Dawley , Proteínas Recombinantes
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