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1.
BMC Musculoskelet Disord ; 25(1): 549, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010020

RESUMO

OBJECTIVE: In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. METHODS: All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. RESULTS: A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535). CONCLUSION: The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.


Assuntos
Tecido Adiposo , Dor Crônica , Dor Lombar , Vértebras Lombares , Imageamento por Ressonância Magnética , Músculos Paraespinais , Humanos , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Masculino , Dor Lombar/diagnóstico por imagem , Dor Lombar/etiologia , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Dor Crônica/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologia
2.
J Transl Med ; 22(1): 661, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010137

RESUMO

BACKGROUND: From the first steps of prostate cancer (PCa) initiation, tumours are in contact with the most-proximal adipose tissue called periprostatic adipose tissue (PPAT). Extracellular vesicles are important carriers of non-coding RNA such as miRNAs that are crucial for cellular communication. The secretion of extracellular vesicles by PPAT may play a key role in the interactions between adipocytes and tumour. Analysing the PPAT exovesicles (EVs) derived-miRNA content can be of great relevance for understanding tumour progression and aggressiveness. METHODS: A total of 24 samples of human PPAT and 17 samples of perivesical adipose tissue (PVAT) were used. EVs were characterized by western blot and transmission electron microscopy (TEM), and uptake by PCa cells was verified by confocal microscopy. PPAT and PVAT explants were cultured overnight, EVs were isolated, and miRNA content expression profile was analysed. Pathway and functional enrichment analyses were performed seeking potential miRNA targets. In vitro functional studies were evaluated using PCa cells lines, miRNA inhibitors and target gene silencers. RESULTS: Western blot and TEM revealed the characteristics of EVs derived from PPAT (PPAT-EVs) samples. The EVs were up taken and found in the cytoplasm of PCa cells. Nine miRNAs were differentially expressed between PPAT and PVAT samples. The RORA gene (RAR Related Orphan Receptor A) was identified as a common target of 9 miRNA-regulated pathways. In vitro functional analysis revealed that the RORA gene was regulated by PPAT-EVs-derived miRNAs and was found to be implicated in cell proliferation and inflammation. CONCLUSION: Tumour periprostatic adipose tissue is linked to PCa tumour aggressiveness and could be envisaged for new therapeutic strategies.


Assuntos
Tecido Adiposo , Proliferação de Células , Vesículas Extracelulares , Regulação Neoplásica da Expressão Gênica , Inflamação , MicroRNAs , Neoplasias da Próstata , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Inflamação/patologia , Inflamação/genética , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Próstata/patologia , Próstata/metabolismo
3.
J Biomed Sci ; 31(1): 71, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004727

RESUMO

BACKGROUND: Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal "cellular-cocktail" prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI. METHODS: Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach. RESULTS: AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified. CONCLUSIONS: The combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.).


Assuntos
Tecido Adiposo , Modelos Animais de Doenças , Isquemia , Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , Camundongos Nus , Animais , Camundongos , Isquemia/terapia , Isquemia/fisiopatologia , Cordão Umbilical/citologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Neovascularização Fisiológica , Células Endoteliais , Humanos
4.
Clin Interv Aging ; 19: 1259-1272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011312

RESUMO

Postmenopausal osteoporosis (PMOP) is a major health problem affecting millions of women worldwide. PMOP patients are often accompanied by abnormal accumulation of bone marrow adipose tissue (BMAT). BMAT is a critical regulator of bone homeostasis, and an increasing BMAT volume is negatively associated with bone mass reduction or fracture. BMAT regulates bone metabolism via adipokines, cytokines and the immune system, but the specific mechanisms are largely unknown. This review emphasizes the impact of estrogen deficiency on bone homeostasis and BMAT expansion, and the mechanism by which BMAT regulates PMOP, providing a promising strategy for targeting BMAT in preventing and treating PMOP.


Assuntos
Tecido Adiposo , Medula Óssea , Osteoporose Pós-Menopausa , Humanos , Tecido Adiposo/metabolismo , Feminino , Densidade Óssea , Adipocinas/metabolismo , Estrogênios/metabolismo , Osso e Ossos/metabolismo , Animais , Citocinas/metabolismo , Homeostase
5.
Function (Oxf) ; 5(4)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38984977

RESUMO

Cholesteryl ester transfer protein (CETP) increases the atherosclerosis risk by lowering HDL-cholesterol levels. It also exhibits tissue-specific effects independent of HDL. However, sexual dimorphism of CETP effects remains largely unexplored. Here, we hypothesized that CETP impacts the perivascular adipose tissue (PVAT) phenotype and function in a sex-specific manner. PVAT function, gene and protein expression, and morphology were examined in male and female transgenic mice expressing human or simian CETP and their non-transgenic counterparts (NTg). PVAT exerted its anticontractile effect in aortas from NTg males, NTg females, and CETP females, but not in CETP males. CETP male PVAT had reduced NO levels, decreased eNOS and phospho-eNOS levels, oxidative stress, increased NOX1 and 2, and decreased SOD2 and 3 expressions. In contrast, CETP-expressing female PVAT displayed increased NO and phospho-eNOS levels with unchanged NOX expression. NOX inhibition and the antioxidant tempol restored PVAT anticontractile function in CETP males. Ex vivo estrogen treatment also restored PVAT function in CETP males. Moreover, CETP males, but not female PVAT, show increased inflammatory markers. PVAT lipid content increased in CETP males but decreased in CETP females, while PVAT cholesterol content increased in CETP females. CETP male PVAT exhibited elevated leptin and reduced Prdm16 (brown adipocyte marker) expression. These findings highlight CETP sex-specific impact on PVAT. In males, CETP impaired PVAT anticontractile function, accompanied by oxidative stress, inflammation, and whitening. Conversely, in females, CETP expression increased NO levels, induced an anti-inflammatory phenotype, and preserved the anticontractile function. This study reveals sex-specific vascular dysfunction mediated by CETP.


Assuntos
Tecido Adiposo , Proteínas de Transferência de Ésteres de Colesterol , Camundongos Transgênicos , Estresse Oxidativo , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/genética , Animais , Masculino , Feminino , Camundongos , Tecido Adiposo/metabolismo , Humanos , Caracteres Sexuais , Óxido Nítrico/metabolismo
6.
Tech Coloproctol ; 28(1): 81, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980511

RESUMO

BACKGROUND: Adipose tissue injections, a rich source of mesenchymal stem cells, have been successfully used to promote anal fistula healing. This study aimed to investigate the efficacy of adipose tissue injection in treating patients with complex and recurrent fistulas of cryptoglandular origin. METHODS: We conducted a prospective, single-center, open-label, non-randomized, interventional clinical trial from January 2020 to December 2022. We enrolled nine patients, who were evaluated after at least 12 months of follow-up. All patients had seton removal, fistula tract excision or curettage, and a mucosal flap if possible or, alternatively, an internal opening suture. We used a commercially available system to collect and process adipose tissue prior to injection. This system allowed the collection, microfragmentation, and filtration of tissue. RESULTS: Selected cases included six men and three women with a median age of 42 (range 31-55) years. All patients had an extended disease course period, ranging from 3 to 13 (mean 6.6) years, and a history of multiple previous surgeries, including two to eight interventions (a mean of 4.4 per case). All fistulas were high transsphincteric, four cases horseshoe and two cases with secondary suprasphincteric or peri-elevator tract fistulas. Six cases (66%) achieved complete fistula healing at a mean follow-up of 18 (range 12-36) months. Three cases (33.3%) experienced reduced secretion and decreased anal discomfort. CONCLUSIONS: In patients with complex and recurrent fistulas, such as the ones described, many from palliative treatments with setons, the adjuvant injection of adipose tissue might help achieve complete healing or improvement in a significant percentage of cases. CLINICALTRIALS: The study protocol was prospectively registered on ClinicalTrials.gov (NCT04750499).


Assuntos
Tecido Adiposo , Fístula Retal , Recidiva , Humanos , Masculino , Feminino , Fístula Retal/terapia , Fístula Retal/cirurgia , Pessoa de Meia-Idade , Adulto , Tecido Adiposo/transplante , Estudos Prospectivos , Resultado do Tratamento , Transplante Autólogo , Injeções , Canal Anal/cirurgia
7.
Front Endocrinol (Lausanne) ; 15: 1353087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978618

RESUMO

More than 619 million people in the world suffer from low back pain (LBP). As two potential inducers of LBP, intervertebral disc degeneration (IVDD) and fat infiltration of paraspinal muscles (PSMs) have attracted extensive attention in recent years. So far, only one review has been presented to summarize their relationship and relevant mechanisms. Nevertheless, it has several noticeable drawbacks, such as incomplete categorization and discussion, lack of practical proposals, etc. Consequently, this paper aims to systematically summarize and classify the interaction between IVDD and fat infiltration of PSMs, thus providing a one-stop search handbook for future studies. As a result, four mechanisms of IVDD leading to fat infiltration of PSMs and three mechanisms of fat infiltration in PSMs causing IVDD are thoroughly analyzed and summarized. The typical reseaches are tabulated and evaluated from four aspects, i.e., methods, conclusions, benefits, and drawbacks. We find that IVDD and fat infiltration of PSMs is a vicious cycle that can promote the occurrence and development of each other, ultimately leading to LBP and disability. Finally, eight perspectives are proposed for future in-depth research.


Assuntos
Tecido Adiposo , Degeneração do Disco Intervertebral , Dor Lombar , Vértebras Lombares , Músculos Paraespinais , Humanos , Músculos Paraespinais/patologia , Degeneração do Disco Intervertebral/patologia , Tecido Adiposo/patologia , Tecido Adiposo/metabolismo , Vértebras Lombares/patologia , Dor Lombar/patologia , Dor Lombar/etiologia
8.
Front Endocrinol (Lausanne) ; 15: 1379293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978626

RESUMO

Background: Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder with wide-ranging metabolic implications, including obesity. RNA editing, a post-transcriptional modification, can fine-tune protein function and introduce heterogeneity. However, the role of RNA editing and its impact on adipose tissue function in PCOS remain poorly understood. Methods: This study aimed to comprehensively analyze RNA-editing events in abdominal and subcutaneous adipose tissue of PCOS patients and healthy controls using high-throughput whole-genome sequencing (WGS) and RNA sequencing. Results: Our results revealed that PCOS patients exhibited more RNA-editing sites, with adenosine-to-inosine (A-to-I) editing being prevalent. The expression of ADAR genes, responsible for A-to-I editing, was also higher in PCOS. Aberrant RNA-editing sites in PCOS adipose tissue was enriched in immune responses, and interleukin-12 biosynthetic process. Tumor necrosis factor (TNF) signaling, nuclear factor kappa B (NF-κB) signaling, Notch signaling, terminal uridylyl transferase 4 (TUT4), hook microtubule tethering protein 3 (HOOK3), and forkhead box O1 (FOXO1) were identified to be of significant differences. Differentially expressed genes (DEGs) in PCOS adipose tissue were enriched in immune responses compared with controls, and the DEGs between subcutaneous and abdominal adipose tissue were also enriched in immune responses suggesting the important role of subcutaneous adipose tissue. Furthermore, we identified the correlations between RNA editing levels and RNA expression levels of specific genes, such as ataxia-telangiectasia mutated (ATM) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) in inflammation pathways and ATM, TUT4, and YTH N6-methyladenosine RNA-binding protein C2 (YTHDC2) in oocyte development pathway. Conclusions: These findings suggest that RNA-editing dysregulation in PCOS adipose tissue may contribute to inflammatory dysregulations. Understanding the interplay between RNA editing and adipose tissue function may unveil potential therapeutic targets for PCOS management. However, further research and validation are required to fully elucidate the molecular mechanisms underlying these associations.


Assuntos
Tecido Adiposo , Obesidade , Síndrome do Ovário Policístico , Edição de RNA , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/patologia , Feminino , Obesidade/genética , Obesidade/metabolismo , Adulto , Tecido Adiposo/metabolismo , Estudos de Casos e Controles , Sequenciamento Completo do Genoma
9.
Sci Adv ; 10(28): eadn2831, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996032

RESUMO

Bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (ADSVF) are the most marketed stem cell therapies to treat a variety of conditions in the general population and elite athletes. Both tissues have been used interchangeably clinically even though their detailed composition, heterogeneity, and mechanisms of action have neither been rigorously inventoried nor compared. This lack of information has prevented investigations into ideal dosages and has facilitated anecdata and misinformation. Here, we analyzed single-cell transcriptomes, proteomes, and flow cytometry profiles from paired clinical-grade BMAC and ADSVF. This comparative transcriptional atlas challenges the prevalent notion that there is one therapeutic cell type present in both tissues. We also provide data of surface markers that may enable isolation and investigation of cell (sub)populations. Furthermore, the proteome atlas highlights intertissue and interpatient heterogeneity of injected proteins with potentially regenerative or immunomodulatory capacities. An interactive webtool is available online.


Assuntos
Células-Tronco Mesenquimais , Proteoma , Proteômica , Análise de Célula Única , Humanos , Proteômica/métodos , Proteoma/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Análise de Célula Única/métodos , Tecido Adiposo/metabolismo , Transcriptoma , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Perfilação da Expressão Gênica
10.
Clinics (Sao Paulo) ; 79: 100430, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38991370

RESUMO

INTRODUCTION: Type 2 Diabetes (T2D) is associated with fractures, despite preserved Bone Mineral Density (BMD). This study aimed to evaluate the relationship between BMD and trabecular bone score (TBS) with the reallocation of fat within muscle in individuals with eutrophy, obesity, and T2D. METHODS: The subjects were divided into three groups: eutrophic controls paired by age and sex with the T2D group (n = 23), controls diagnosed with obesity paired by age, sex, and body mass index with the T2D group (n = 27), and the T2D group (n = 29). BMD and body fat percentage were determined using dual-energy X-Ray absorptiometry. TBS was determined using TBS iNsight software. Intra and extramyocellular lipids in the soleus were measured using proton magnetic resonance spectroscopy. RESULTS: TBS was lower in the T2D group than in the other two groups. Glycated hemoglobin (A1c) was negatively associated with TBS. Body fat percentage was negatively associated with TBS and Total Hip (TH) BMD. TH BMD was positively associated with intramuscular lipids. A trend of negative association was observed between intramuscular lipids and TBS. CONCLUSION: This study showed for the first time that the reallocation of lipids within muscle has a negative association with TBS. Moreover, these results are consistent with previous studies showing a negative association between a parameter related to insulin resistance (intramuscular lipids) and TBS.


Assuntos
Absorciometria de Fóton , Tecido Adiposo , Densidade Óssea , Osso Esponjoso , Diabetes Mellitus Tipo 2 , Músculo Esquelético , Humanos , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Densidade Óssea/fisiologia , Osso Esponjoso/diagnóstico por imagem , Estudos de Casos e Controles , Tecido Adiposo/diagnóstico por imagem , Adulto , Obesidade/fisiopatologia , Obesidade/metabolismo , Hemoglobinas Glicadas/análise , Índice de Massa Corporal , Idoso , Controle Glicêmico , Valores de Referência
11.
Sci Rep ; 14(1): 16093, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997312

RESUMO

Adipose tissue plays critical roles in an individual's aging process. In this research, we use single-nucleus RNA sequencing to create highly detailed transcriptional maps of subcutaneous adipose tissue and visceral adipose tissue in young and aged mice. We comprehensively identify the various cell types within the white adipose tissue of mice, our study has elucidated seven distinct cell types within this tissue. Further analyses focus on adipocytes, fibro-adipogenic progenitors, and immune cells, revealing age-related declines in the synthetic metabolic activity of adipocytes, diminished immune regulation, and reduced maturation or proliferation of fibroblasts in undifferentiated adipocytes. We confirm the presence of distinct subpopulations of adipocytes, highlighting decreases in adipogenesis subgroups due to aging. Additionally, we uncover a reduction in immune cell subpopulations, driven by age-associated immune system dysregulation. Furthermore, pseudo-time analyses indicate that Adipocyte1 represents the 'nascent' phase of adipocyte development, while Adipocyte2 represents the 'mature' phase. We use cell-cell interaction to explore the age-dependent complexities of the interactions between FAPs and adipocytes, and observed increased expression of the inflammation-related Retn-Tlr4 interaction in older mice, while the anti-inflammatory Angpt1-Tek interaction was only detected in young mice. These transcriptional profiles serve as a valuable resource for understanding the functional genomics underlying metabolic disorders associated with aging in human adipose tissue.


Assuntos
Adipócitos , Envelhecimento , Perfilação da Expressão Gênica , Animais , Envelhecimento/genética , Camundongos , Adipócitos/metabolismo , Transcriptoma , Adipogenia/genética , Tecido Adiposo/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Tecido Adiposo Branco/metabolismo , Análise de Célula Única
12.
Sci Rep ; 14(1): 16109, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997324

RESUMO

This work was inspired by the observation that a majority of MR-electrical properties tomography studies are based on direct comparisons with ex vivo measurements carried out on post-mortem samples in the 90's. As a result, the in vivo conductivity values obtained from MRI in the megahertz range in different types of tissues (brain, liver, tumors, muscles, etc.) found in the literature may not correspond to their ex vivo equivalent, which still serves as a reference for electromagnetic modelling. This study aims to pave the way for improving current databases since the definition of personalized electromagnetic models (e.g. for Specific Absorption Rate estimation) would benefit from better estimation. Seventeen healthy volunteers underwent MRI of both brain and thorax/abdomen using a three-dimensional ultrashort echo-time (UTE) sequence. We estimated conductivity (S/m) in several classes of macroscopic tissue using a customized reconstruction method from complex UTE images, and give general statistics for each of these regions (mean-median-standard deviation). These values are used to find possible correlations with biological parameters such as age, sex, body mass index and/or fat volume fraction, using linear regression analysis. In short, the collected in vivo values show significant deviations from the ex vivo values in conventional databases, and we show significant relationships with the latter parameters in certain organs for the first time, e.g. a decrease in brain conductivity with age.


Assuntos
Encéfalo , Condutividade Elétrica , Imageamento por Ressonância Magnética , Tronco , Humanos , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Adulto , Pessoa de Meia-Idade , Tronco/diagnóstico por imagem , Idoso , Fatores Etários , Adulto Jovem , Fatores Sexuais , Tecido Adiposo/diagnóstico por imagem
13.
Nutrients ; 16(13)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38999741

RESUMO

BN-202M is derived from humans and consists of two strains, Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53. Body fat reduction effect and safety of BN-202M were assessed in overweight participants. A total of 150 participants were randomly assigned to the BN-202M and placebo groups at a 1:1 ratio. Dual-energy X-ray absorptiometry was used to objectively measure body fat. After 12 weeks of oral administration, the body fat percentage (-0.10 ± 1.32% vs. 0.48 ± 1.10%; p = 0.009) and body fat mass (-0.24 ± 1.19 kg vs. 0.23 ± 1.05 kg; p = 0.023) of the BN-202M group decreased significantly compared to those of the placebo group. The body weight (-0.58 kg, p = 0.004) and body mass index (BMI; -0.23, p = 0.003) was found to decrease significantly at 12 weeks in the BN-202M group, but not in the placebo group. Metabolome analysis revealed that ß-alanine, 3-aminoisobutyric acid, glutamic acid, and octopamine decreased in the weight-decreased BN-202M post-intake group. In the gut microbiota analysis, Akkermansia showed a statistically significant increase in the BN-202M group post-intake compared to the placebo group. No serious adverse events were observed in either group. These results suggest that BN-202M is safe and effective for reducing body fat and weight.


Assuntos
Tecido Adiposo , Sobrepeso , Probióticos , Humanos , Masculino , Feminino , Método Duplo-Cego , Probióticos/administração & dosagem , Adulto , Pessoa de Meia-Idade , Tecido Adiposo/metabolismo , Lacticaseibacillus paracasei , Índice de Massa Corporal , Lactobacillus plantarum , Absorciometria de Fóton
14.
Nutrients ; 16(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38999894

RESUMO

Pre-pregnancy body mass index (pBMI) is a predictor of gestational weight gain (GWG). However, other factors, such as adipokines and inflammation markers, may also be associated with GWG. The aim of the study was to determine the association of leptin, adiponectin, irisin, and C-reactive protein, with GWG in adolescents. A longitudinal study was conducted from 2018 to 2023 in adolescents with a clinically healthy pregnancy. The assessments included sociodemographic and clinical data, pBMI, percent of body fat, serum concentrations of leptin, adiponectin, irisin, and high-sensitivity C-reactive protein (hsCRP), and total GWG adequacy. Cox regression models were performed, the outcome variables were inadequate and excessive GWG. In 198 participants, being overweight/obesity was marginally associated with a protective effect against inadequate GWG (HR = 0.44, 95%CI = 0.18-1.06), regardless of maternal characteristics and adipokines. Leptin (HR = 1.014, 95%CI = 1.008-1.021), and body fat percent (HR = 1.11, 95%CI = 1.05-1.17) were associated with a higher risk of excessive GWG, independent of other maternal variables such as pBMI, while adiponectin was associated with a lower risk. These findings suggest that, in Mexican adolescents, adipose tissue and its adipokines during pregnancy may play a more significant role in the final GWG than body weight.


Assuntos
Adipocinas , Tecido Adiposo , Índice de Massa Corporal , Ganho de Peso na Gestação , Leptina , Humanos , Feminino , Gravidez , Leptina/sangue , Adolescente , México/epidemiologia , Adipocinas/sangue , Estudos Longitudinais , Adiponectina/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo
15.
Nutrients ; 16(13)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38999907

RESUMO

BACKGROUND: Obesity constitutes a public health problem worldwide and causes non-alcoholic fatty liver disease (MALFD), the leading cause of liver disease in developed countries, which progresses to liver cirrhosis and liver cancer. MAFLD is associated with obesity and can be evaluated by validated formulas to assess MAFLD risk using different parameters such as the body mass index (BMI) and waist circumference (WC). However, these parameters do not accurately measure body fat. As MAFLD is strongly associated with obesity, we hypothesize that measuring body and visceral fat by electrical bioimpedance is an efficient method to predict the risk of MAFLD. The objective of our work was to demonstrate that electrical bioimpedance is a more efficient method than the BMI or WC to predict an elevated risk of MAFLD. METHODS: A cross-sectional, descriptive study involving 8590 Spanish workers in the Balearic Islands was carried out. The study's sample of employees was drawn from those who underwent occupational medicine examinations between January 2019 and December 2020. Five MAFLD risk scales were determined for evaluating very high levels of body fat and visceral fat. The determination of body and visceral fat was performed using bioimpedanciometry. Student's t-test was employed to ascertain the mean and standard deviation of quantitative data. The chi-square test was used to find prevalences for qualitative variables, while ROC curves were used to define the cut-off points for body and visceral fat. The calculations included the area under the curve (AUC), the cut-off points along with their Youden index, sensitivity, and specificity. Correlation and concordance between the various scales were determined using Pearson's correlation index and Cohen's kappa, respectively. RESULTS: As both total body fat and visceral fat increase, the risk of MAFLD increases with a statistically significant result (p < 0.001), presenting a higher risk in men. The areas under the curve (AUC) of the five scales that assess overweight and obesity to determine the occurrence of high values of the different MAFLD risk scales were very high, most of them exceeding 0.9. These AUC values were higher for visceral and body fat than for the BMI or waist circumference. FLD-high presented the best results in men and women with the AUC at around 0.97, both for visceral fat and total body fat, with a high Youden index in all cases (women body fat = 0.830, visceral fat = 0.892; men body fat = 0.780, visceral fat = 0.881). CONCLUSIONS: In our study, all the overweight and obesity scales show a very good association with the scales assessing the risk of MAFLD. These values are higher for visceral and body fat than for waist circumference and the BMI. Both visceral fat and body fat are better associated than the BMI and waist circumference with MAFLD risk scales.


Assuntos
Tecido Adiposo , Impedância Elétrica , Gordura Intra-Abdominal , Hepatopatia Gordurosa não Alcoólica , Medição de Risco , Gordura Intra-Abdominal/metabolismo , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Espanha , Estudos Transversais , Medição de Risco/métodos , Valor Preditivo dos Testes , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Idoso
16.
Nutrients ; 16(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38999918

RESUMO

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1ß and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.


Assuntos
Células 3T3-L1 , Adipogenia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Extratos Vegetais , Aumento de Peso , Animais , Dieta Hiperlipídica/efeitos adversos , Extratos Vegetais/farmacologia , Camundongos , Aumento de Peso/efeitos dos fármacos , Masculino , Adipogenia/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Obesidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo
17.
Int J Mol Sci ; 25(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38999932

RESUMO

The World Health Organization (WHO) highlights a greater susceptibility of males to tuberculosis (TB), a vulnerability attributed to sex-specific variations in body fat and dietary factors. Our study delves into the unexplored terrain of how alterations in body fat influence Mycobacterium tuberculosis (Mtb) burden, lung pathology, immune responses, and gene expression, with a focus on sex-specific dynamics. Utilizing a low-dose Mtb-HN878 clinical strain infection model, we employ transgenic FAT-ATTAC mice with modulable body fat to explore the impact of fat loss (via fat ablation) and fat gain (via a medium-fat diet, MFD). Firstly, our investigation unveils that Mtb infection triggers severe pulmonary pathology in males, marked by shifts in metabolic signaling involving heightened lipid hydrolysis and proinflammatory signaling driven by IL-6 and localized pro-inflammatory CD8+ cells. This stands in stark contrast to females on a control regular diet (RD). Secondly, our findings indicate that both fat loss and fat gain in males lead to significantly elevated (1.6-fold (p ≤ 0.01) and 1.7-fold (p ≤ 0.001), respectively) Mtb burden in the lungs compared to females during Mtb infection (where fat loss and gain did not alter Mtb load in the lungs). This upsurge is associated with impaired lung lipid metabolism and intensified mitochondrial oxidative phosphorylation-regulated activity in lung CD8+ cells during Mtb infection. Additionally, our research brings to light that females exhibit a more robust systemic IFNγ (p ≤ 0.001) response than males during Mtb infection. This heightened response may either prevent active disease or contribute to latency in females during Mtb infection. In summary, our comprehensive analysis of the interplay between body fat changes and sex bias in Mtb infection reveals that alterations in body fat critically impact pulmonary pathology in males. Specifically, these changes significantly reduce the levels of pulmonary CD8+ T-cells and increase the Mtb burden in the lungs compared to females. The reduction in CD8+ cells in males is linked to an increase in mitochondrial oxidative phosphorylation and a decrease in TNFα, which are essential for CD8+ cell activation.


Assuntos
Tecido Adiposo , Pulmão , Mycobacterium tuberculosis , Animais , Feminino , Masculino , Camundongos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Pulmão/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia , Tuberculose Pulmonar/microbiologia , Camundongos Transgênicos , Fatores Sexuais , Modelos Animais de Doenças , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Caracteres Sexuais , Camundongos Endogâmicos C57BL
18.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000134

RESUMO

Stem cells possess the ability to differentiate into different lineages and the ability to self-renew, thus representing an excellent tool for regenerative medicine. They can be isolated from different tissues, including the adipose tissue. Adipose tissue and human adipose-derived stem cells (hADSCs) are privileged candidates for regenerative medicine procedures or other plastic reconstructive surgeries. The cellular environment is able to influence the fate of stem cells residing in the tissue. In a previous study, we exposed hADSCs to an exhausted medium of a breast cancer cell line (MCF-7) recovered at different days (4, 7, and 10 days). In the same paper, we inferred that the medium was able to influence the behaviour of stem cells. Considering these results, in the present study, we evaluated the expression of the major genes related to adipogenic and osteogenic differentiation. To confirm the gene expression data, oil red and alizarin red colorimetric assays were performed. Lastly, we evaluated the expression of miRNAs influencing the differentiation process and the proliferation rate, maintaining a proliferative state. The data obtained confirmed that cells exposed to the medium maintained a stem and proliferative state that could lead to a risky proliferative phenotype.


Assuntos
Tecido Adiposo , Diferenciação Celular , Proliferação de Células , Osteogênese , Humanos , Diferenciação Celular/efeitos dos fármacos , Células MCF-7 , Proliferação de Células/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Adipogenia/genética , Células-Tronco/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Meios de Cultura/farmacologia , Meios de Cultura/química
19.
Front Immunol ; 15: 1356397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975341

RESUMO

Introduction: Within adipose tissue (AT), different macrophage subsets have been described, which played pivotal and specific roles in upholding tissue homeostasis under both physiological and pathological conditions. Nonetheless, studying resident macrophages in-vitro poses challenges, as the isolation process and the culture for extended periods can alter their inherent properties. Methods: Stroma-vascular cells isolated from murine subcutaneous AT were seeded on ultra-low adherent plates in the presence of macrophage colony-stimulating factor. After 4 days of culture, the cells spontaneously aggregate to form spheroids. A week later, macrophages begin to spread out of the spheroid and adhere to the culture plate. Results: This innovative three-dimensional (3D) culture method enables the generation of functional mature macrophages that present distinct genic and phenotypic characteristics compared to bone marrow-derived macrophages. They also show specific metabolic activity and polarization in response to stimulation, but similar phagocytic capacity. Additionally, based on single-cell analysis, AT-macrophages generated in 3D culture mirror the phenotypic and functional traits of in-vivo AT resident macrophages. Discussion: Our study describes a 3D in-vitro system for generating and culturing functional AT-resident macrophages, without the need for cell sorting. This system thus stands as a valuable resource for exploring the differentiation and function of AT-macrophages in vitro in diverse physiological and pathological contexts.


Assuntos
Tecido Adiposo , Técnicas de Cultura de Células em Três Dimensões , Diferenciação Celular , Macrófagos , Animais , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Tecido Adiposo/citologia , Técnicas de Cultura de Células em Três Dimensões/métodos , Células Cultivadas , Fagocitose , Camundongos Endogâmicos C57BL , Esferoides Celulares/citologia , Técnicas de Cultura de Células/métodos , Fenótipo
20.
Front Endocrinol (Lausanne) ; 15: 1404697, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38982993

RESUMO

Adipose tissue, an indispensable organ, fulfils the pivotal role of energy storage and metabolism and is instrumental in maintaining the dynamic equilibrium of energy and health of the organism. Adipocyte hypertrophy and adipocyte hyperplasia (adipogenesis) are the two primary mechanisms of fat deposition. Mature adipocytes are obtained by differentiating mesenchymal stem cells into preadipocytes and redifferentiation. However, the mechanisms orchestrating adipogenesis remain unclear. Autophagy, an alternative cell death pathway that sustains intracellular energy homeostasis through the degradation of cellular components, is implicated in regulating adipogenesis. Furthermore, adipose tissue functions as an endocrine organ, producing various cytokines, and certain inflammatory factors, in turn, modulate autophagy and adipogenesis. Additionally, autophagy influences intracellular redox homeostasis by regulating reactive oxygen species, which play pivotal roles in adipogenesis. There is a growing interest in exploring the involvement of autophagy, inflammation, and oxidative stress in adipogenesis. The present manuscript reviews the impact of autophagy, oxidative stress, and inflammation on the regulation of adipogenesis and, for the first time, discusses their interactions during adipogenesis. An integrated analysis of the role of autophagy, inflammation and oxidative stress will contribute to elucidating the mechanisms of adipogenesis and expediting the exploration of molecular targets for treating obesity-related metabolic disorders.


Assuntos
Adipogenia , Autofagia , Inflamação , Estresse Oxidativo , Adipogenia/fisiologia , Humanos , Autofagia/fisiologia , Estresse Oxidativo/fisiologia , Inflamação/metabolismo , Inflamação/patologia , Animais , Adipócitos/metabolismo , Adipócitos/patologia , Obesidade/metabolismo , Obesidade/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia
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