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1.
J. physiol. biochem ; 80(1): 41-51, Feb. 2024. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-229939

RESUMO

Parkin is an ubiquitin‐E3 ligase that is involved in cellular mitophagy and was recently shown to contribute to controlling adipose tissue thermogenic plasticity. We found that Parkin expression is induced in brown (BAT) and white (WAT) adipose tissues of aged mice. We determined the potential role of Parkin in the aging-associated decline in the thermogenic capacity of adipose tissues by analyzing subcutaneous WAT, interscapular BAT, and systemic metabolic and physiological parameters in young (5 month-old) and aged (16 month-old) mice with targeted invalidation of the Parkin (Park2) gene, and their wild-type littermates. Our data indicate that suppression of Parkin prevented adipose accretion, increased energy expenditure and improved the systemic metabolic derangements, such as insulin resistance, seen in aged mice. This was associated with maintenance of browning and reduction of the age-associated induction of inflammation in subcutaneous WAT. BAT in aged mice was much less affected by Parkin gene invalidation. Such protection was associated with a dramatic prevention of the age-associated induction of fibroblast growth factor-21 (FGF21) levels in aged Parkin-invalidated mice. This was associated with a parallel reduction in FGF21 gene expression in adipose tissues and liver in aged Parkin-invalidated mice. Additionally, Parkin invalidation prevented the protein down-regulation of β-Klotho (a key co-receptor mediating FGF21 responsiveness in tissues) in aged adipose tissues. We conclude that Parkin down-regulation leads to improved systemic metabolism in aged mice, in association with maintenance of adipose tissue browning and FGF21 system functionality. (AU)


Assuntos
Animais , Camundongos , Proteínas Associadas à Doença de Parkinson , Peptídeos e Proteínas de Sinalização Intercelular , Envelhecimento , Tecido Adiposo , Metabolismo
2.
Front Immunol ; 15: 1326953, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361943

RESUMO

Objectives: In knee osteoarthritis (OA), macrophages are the most predominant immune cells that infiltrate synovial tissues and infrapatellar fat pads (IPFPs). Both M1 and M2 macrophages have been described, but their role in OA has not been fully investigated. Therefore, we investigated macrophage subpopulations in IPFPs and synovial tissues of knee OA patients and their correlation with disease severity, examined their transcriptomics, and tested for factors that influenced their polarization. Methods: Synovial tissues and IPFPs were obtained from knee OA patients undergoing total knee arthroplasty. Macrophages isolated from these joint tissues were characterized via flow cytometry. Transcriptomic profiling of each macrophage subpopulations was performed using NanoString technology. Peripheral blood monocyte-derived macrophages (MDMs) were treated with synovial fluid and synovial tissue- and IPFP-conditioned media. Synovial fluid-treated MDMs were treated with platelet-rich plasma (PRP) and its effects on macrophage polarization were observed. Results: Our findings show that CD11c+CD206+ macrophages were predominant in IPFPs and synovial tissues compared to other macrophage subpopulations (CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages) of knee OA patients. The abundance of macrophages in IPFPs reflected those in synovial tissues but did not correlate with disease severity as determined from Mankin scoring of cartilage destruction. Our transcriptomics data demonstrated highly expressed genes that were related to OA pathogenesis in CD11c+CD206+ macrophages than CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages. In addition, MDMs treated with synovial fluid, synovial tissue-conditioned media, or IPFP-conditioned media resulted in different polarization profiles of MDMs. IPFP-conditioned media induced increases in CD86+CD206+ MDMs, whereas synovial tissue-conditioned media induced increases in CD86+CD206- MDMs. Synovial fluid treatment (at 1:8 dilution) induced a very subtle polarization in each macrophage subpopulation. PRP was able to shift macrophage subpopulations and partially reverse the profiles of synovial fluid-treated MDMs. Conclusion: Our study provides an insight on the phenotypes and genotypes of macrophages found in IPFPs and synovial tissues of knee OA patients. We also show that the microenvironment plays a role in driving macrophages to polarize differently and shifting macrophage profiles can be reversed by PRP.


Assuntos
Tecido Adiposo , Osteoartrite do Joelho , Humanos , Meios de Cultivo Condicionados , Tecido Adiposo/patologia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/patologia , Macrófagos/patologia , Fenótipo , Genótipo
3.
Lipids Health Dis ; 23(1): 49, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38365763

RESUMO

Globally, obesity and asthma pose significant health challenges, with obesity being a key factor influencing asthma. Despite this, effective treatments for obese asthma, a distinct phenotype, remain elusive. Since the discovery of transient receptor potential (TRP) channels in 1969, their value as therapeutic targets for various diseases has been acknowledged. TRP channels, present in adipose tissue cells, influence fat cell heat production and the secretion of adipokines and cytokines, which are closely associated with asthma and obesity. This paper aims to investigate the mechanisms by which obesity exacerbates asthma-related inflammation and suggests that targeting TRP channels in adipose tissue could potentially suppress obese asthma and offer novel insights into its treatment.


Assuntos
Asma , Canais de Potencial de Receptor Transitório , Humanos , Canais de Potencial de Receptor Transitório/genética , Obesidade/complicações , Obesidade/genética , Asma/tratamento farmacológico , Asma/complicações , Tecido Adiposo , Macrófagos , Inflamação/complicações
4.
Commun Biol ; 7(1): 194, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365885

RESUMO

Diet is a key lifestyle component that influences metabolic health through several factors, including total energy intake and macronutrient composition. While the impact of caloric intake on gene expression and physiological phenomena in various tissues is well described, the influence of dietary macronutrient composition on these parameters is less well studied. Here, we use the Nutritional Geometry framework to investigate the role of macronutrient composition on metabolic function and gene regulation in adipose tissue. Using ten isocaloric diets that vary systematically in their proportion of energy from fat, protein, and carbohydrates, we find that gene expression and splicing are highly responsive to macronutrient composition, with distinct sets of genes regulated by different macronutrient interactions. Specifically, the expression of many genes associated with Bardet-Biedl syndrome is responsive to dietary fat content. Splicing and expression changes occur in largely separate gene sets, highlighting distinct mechanisms by which dietary composition influences the transcriptome and emphasizing the importance of considering splicing changes to more fully capture the gene regulation response to environmental changes such as diet. Our study provides insight into the gene regulation plasticity of adipose tissue in response to macronutrient composition, beyond the already well-characterized response to caloric intake.


Assuntos
Tecido Adiposo , Dieta , Gorduras na Dieta , Ingestão de Energia/genética , Nutrientes
5.
Lipids Health Dis ; 23(1): 47, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355592

RESUMO

BACKGROUND: Being overweight or obese has become a serious public health concern, and accurate assessment of body composition is particularly important. More precise indicators of body fat composition include visceral adipose tissue (VAT) mass and total body fat percentage (TBF%). Study objectives included examining the relationships between abdominal fat mass, measured by quantitative computed tomography (QCT), and the whole-body and regional fat masses, measured by dual energy X-ray absorptiometry (DXA), as well as to derive equations for the prediction of TBF% using data obtained from multiple QCT slices. METHODS: Whole-body and regional fat percentage were quantified using DXA in Chinese males (n = 68) and females (n = 71) between the ages of 24 and 88. All the participants also underwent abdominal QCT measurement, and their VAT mass and visceral fat volume (VFV) were assessed using QCT and DXA, respectively. RESULTS: DXA-derived TBF% closely correlated with QCT abdominal fat percentage (r = 0.89-0.93 in men and 0.76-0.88 in women). Stepwise regression showed that single-slice QCT data were the best predictors of DXA-derived TBF%, DXA android fat percentage and DXA gynoid fat percentage. Cross-validation analysis showed that TBF% and android fat percentage could be accurately predicted using QCT data in both sexes. There were close correlations between QCT-derived and DXA-derived VFV (r = 0.97 in men and 0.93 in women). CONCLUSION: Clinicians can assess the TBF% and android and gynoid fat percentages of Chinese women and men by analysing existing abdominal CT-derived data using the QCT technique.


Assuntos
Tecido Adiposo , Composição Corporal , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/metabolismo , Tomografia Computadorizada por Raios X/métodos , Obesidade/metabolismo , Absorciometria de Fóton/métodos , China , Índice de Massa Corporal
6.
Hypertension ; 81(3): 561-571, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354270

RESUMO

BACKGROUND: Small arteries exhibit resting tone, a partially contracted state that maintains arterial blood pressure. In arterial smooth muscle cells, potassium channels control contraction and relaxation. Perivascular adipose tissue (PVAT) has been shown to exert anticontractile effects on the blood vessels. However, the mechanisms by which PVAT signals small arteries, and their relevance remain largely unknown. We aimed to uncover key molecular components in adipose-vascular coupling. METHODS: A wide spectrum of genetic mouse models targeting Kcnq3, Kcnq4, and Kcnq5 genes (Kcnq3-/-, Kcnq4-/-, Kcnq5-/-, Kcnq5dn/dn, Kcnq4-/-/Kcnq5dn/dn, and Kcnq4-/-/Kcnq5-/-), telemetry blood pressure measurements, targeted lipidomics, RNA-Seq profiling, wire-myography, patch-clamp, and sharp-electrode membrane potential measurements was used. RESULTS: We show that PVAT causes smooth muscle cell KV7.5 family of voltage-gated potassium (K+) channels to hyperpolarize the membrane potential. This effect relaxes small arteries and regulates blood pressure. Oxygenation of polyunsaturated fats generates oxylipins, a superclass of lipid mediators. We identified numerous oxylipins released by PVAT, which potentiate vasodilatory action in small arteries by opening smooth muscle cell KV7.5 family of voltage-gated potassium (K+) channels. CONCLUSIONS: Our results reveal a key molecular function of the KV7.5 family of voltage-gated potassium (K+) channels in the adipose-vascular coupling, translating PVAT signals, particularly oxylipins, to the central physiological function of vasoregulation. This novel pathway opens new therapeutic perspectives.


Assuntos
Oxilipinas , Vasodilatação , Camundongos , Animais , Oxilipinas/metabolismo , Canais de Potássio KCNQ/genética , Canais de Potássio KCNQ/metabolismo , Tecido Adiposo , Potássio/metabolismo
7.
Clin Exp Pharmacol Physiol ; 51(3): e13836, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38302078

RESUMO

The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty-four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N-TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H-TBW). Patients with higher PBF and rocuronium were dosed based on fat-free mass (H-FFM). A train of four (TOF)-Watch acceleromyography monitor was used to measure the effects of the rocuronium. H-TBW (91.9 ± 28.8 s) had significantly shorter onset time than N-TBW and H-FFM (p = 0.003). H-TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25-0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time.


Assuntos
Fármacos Neuromusculares não Despolarizantes , Humanos , Rocurônio , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , China , Obesidade , Tecido Adiposo
8.
Mol Biol Rep ; 51(1): 272, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302806

RESUMO

BACKGROUND: Wnt10b is one of critical Wnt family members that being involved in networks controlling stemness, pluripotency and cell fate decisions. However, its role in adipose-resident T lymphocytes and further in fat metabolism yet remains largely unknown. METHODS AND RESULTS: In the present study, we demonstrated a distinctive effect for Wnt10b on the relative balance of T lymphocytes in adipose tissue by using a Wnt10b knockdown mouse model. Wnt10b knockdown led to a reduction of adipose-resident CD4+ T cells and an elevation of Foxp3+/CD4+ Treg cells. Wnt10b-knockdown mice fed with standard diet showed less white fat deposition owing to the suppressed adipogenic process. Moreover, under high fat diet conditions, Wnt10b knockdown resulted in an alleviated obesity symptoms, as well as an improvement of glucose homeostasis and hepatic steatosis. CONCLUSIONS: Collectively, we reveal an unexpected and novel function for Wnt10b in mediating the frequency of adipose-resident T cell subsets, that when knockdown skewing toward a Treg-dominated phenotype and further improving fat metabolism.


Assuntos
Tecido Adiposo Branco , Tecido Adiposo , Camundongos , Animais , Tecido Adiposo/fisiologia , Obesidade/genética , Diferenciação Celular , Adipogenia/genética , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Proteínas Wnt/genética
9.
Proc Natl Acad Sci U S A ; 121(6): e2313185121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38300872

RESUMO

Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages' engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.


Assuntos
Obesidade , Aumento de Peso , Camundongos , Animais , Obesidade/metabolismo , Aumento de Peso/fisiologia , Macrófagos/metabolismo , Colágeno/metabolismo , Inflamação/metabolismo , Colágeno Tipo I/metabolismo , Gordura Subcutânea/metabolismo , Gordura Subcutânea/patologia , Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos
10.
Lasers Med Sci ; 39(1): 58, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334845

RESUMO

Due to its regenerative action, extracorporeal shock wave therapy (ESWT) is applied in treating integumentary and musculoskeletal diseases. However, other potential therapeutic interventions are being investigated. It is essential to fully understand its mitochondrial signaling pathway to achieve this, which plays a fundamental role in elucidating the mechanism of action and possible therapeutic interventions. Thus, this study aimed to analyze the effect of ESWT on mitochondrial pathways through the relationship between lipolysis and adipocyte apoptosis, as well as cellular functionality. This is a non-randomized case-control clinical trial where obese women received ESWT sessions in the abdominal region, after which tissue samples were collected for histological and immunohistochemical analyses of adipose tissue. The data demonstrated positivity in the expression of mitochondrial markers related to cell apoptosis, such as FIS1 (p < 0.0203) and OPA1 (p < 0.0283), in addition to the positivity of anti-MFN1, responsible for regulating mitochondrial cell proliferation (p < 0.0003). In summary, this study demonstrates that ESWT was able to activate specific mitochondrial signaling pathways, which may be associated with its ability to stimulate lipolysis and apoptosis in superficial adipose tissue. However, no significant improvements in cellular functionality were observed.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Feminino , Humanos , Tecido Adiposo , Proliferação de Células , Transdução de Sinais , Pele , Estudos de Casos e Controles
11.
Nutrients ; 16(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38337703

RESUMO

Epicardial adipose tissue (EAT) stands out as a distinctive repository of visceral fat, positioned in close anatomical and functional proximity to the heart. EAT has emerged as a distinctive reservoir of visceral fat, intricately interlinked with cardiovascular health, particularly within the domain of cardiovascular diseases (CVDs). The aim of our overview is to highlight the role of EAT as a marker for cardiovascular risk in children. We also explore the influence of unhealthy lifestyle habits as predisposing factors for the deposition of EAT. The literature data accentuate the consequential impact of lifestyle choices on EAT dynamics, with sedentary behavior and unwholesome dietary practices being contributory to a heightened cardiovascular risk. Lifestyle interventions with a multidisciplinary approach are therefore pivotal, involving a nutritionally balanced diet rich in polyunsaturated and monounsaturated fatty acids, regular engagement in aerobic exercise, and psychosocial support to effectively mitigate cardiovascular risks in children. Specific interventions, such as high-intensity intermittent training and circuit training, reveal favorable outcomes in diminishing the EAT volume and enhancing cardiometabolic health. Future clinical studies focusing on EAT in children are crucial for advancing our understanding and developing targeted strategies for cardiovascular risk management in this population.


Assuntos
Doenças Cardiovasculares , Criança , Humanos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Pericárdio , Fatores de Risco de Doenças Cardíacas , Estilo de Vida , Hábitos , Tecido Adiposo
12.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338737

RESUMO

The therapeutic effect of mesenchymal stromal cells (MSCs) has been described for a variety of disorders, including those affecting musculoskeletal tissues. In this context, the literature reports several data about the regenerative effectiveness of MSCs derived from bone marrow, adipose tissue, and an amniotic membrane (BMSCs, ASCs, and hAMSCs, respectively), either when expanded or when acting as clinical-grade biologic pillars of products used at the point of care. To date, there is no evidence about the superiority of one source over the others from a clinical perspective. Therefore, a reliable characterization of the tissue-specific MSC types is mandatory to identify the most effective treatment, especially when tailored to the target disease. Because molecular characterization is a crucial parameter for cell definition, the need for reliable normalizers as housekeeping genes (HKGs) is essential. In this report, the stability levels of five commonly used HKGs (ACTB, EF1A, GAPDH, RPLP0, and TBP) were sifted into BMSCs, ASCs, and hAMSCs. Adult and fetal/neonatal MSCs showed opposite HKG stability rankings. Moreover, by analyzing MSC types side-by-side, comparison-specific HKGs emerged. The effect of less performant HKG normalization was also demonstrated in genes coding for factors potentially involved in and predicting MSC therapeutic activity for osteoarthritis as a model musculoskeletal disorder, where the choice of the most appropriate normalizer had a higher impact on the donors rather than cell populations when compared side-by-side. In conclusion, this work confirms HKG source-specificity for MSCs and suggests the need for cell-type specific normalizers for cell source or condition-tailored gene expression studies.


Assuntos
Genes Essenciais , Células-Tronco Mesenquimais , Medula Óssea , Diferenciação Celular/genética , Medicina Regenerativa , Âmnio , Tecido Adiposo/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células da Medula Óssea/metabolismo , Células Cultivadas
13.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338780

RESUMO

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.


Assuntos
Leptina , Fístula Retal , Humanos , Resistina , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Resultado do Tratamento , Qualidade de Vida , Adiponectina , Fístula Retal/etiologia , Tecido Adiposo/metabolismo , Caderinas
14.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338972

RESUMO

Computed tomography angiography (CTA) has validated the use of pericoronary adipose tissue (PCAT) attenuation as a credible indicator of coronary inflammation, playing a crucial role in coronary artery disease (CAD). This study aimed to evaluate the long-term effects of high-dose statins on PCAT attenuation at coronary lesion sites and changes in plaque distribution. Our prospective observational study included 52 patients (mean age 60.43) with chest pain, a low-to-intermediate likelihood of CAD, who had documented atheromatous plaque through CTA, performed approximately 1 year and 3 years after inclusion. We utilized the advanced features of the CaRi-Heart® and syngo.via Frontier® systems to assess coronary plaques and changes in PCAT attenuation. The investigation of changes in plaque morphology revealed significant alterations. Notably, in mixed plaques, calcified portions increased (p < 0.0001), while non-calcified plaque volume (NCPV) decreased (p = 0.0209). PCAT attenuation generally decreased after one year and remained low, indicating reduced inflammation in the following arteries: left anterior descending artery (LAD) (p = 0.0142), left circumflex artery (LCX) (p = 0.0513), and right coronary artery (RCA) (p = 0.1249). The CaRi-Heart® risk also decreased significantly (p = 0.0041). Linear regression analysis demonstrated a correlation between increased PCAT attenuation and higher volumes of NCPV (p < 0.0001, r = 0.3032) and lipid-rich plaque volume (p < 0.0001, r = 0.3281). Our study provides evidence that high-dose statin therapy significantly reduces CAD risk factors, inflammation, and plaque vulnerability, as evidenced by the notable decrease in PCAT attenuation, a critical indicator of plaque progression.


Assuntos
Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Placa Aterosclerótica , Humanos , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/patologia , Angiografia por Tomografia Computadorizada/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Seguimentos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Tecido Adiposo
15.
Int J Mol Sci ; 25(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38339081

RESUMO

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.


Assuntos
Adipogenia , Microbioma Gastrointestinal , Humanos , Cafeína/farmacologia , Cafeína/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Dieta Hiperlipídica
16.
PLoS One ; 19(2): e0292872, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38330039

RESUMO

The present Systematic Review with Meta-analysis study aimed to evaluate the validity and reliability of the Portable A-mode Ultrasound (P-US) for measuring body fat percentage (BF%). Only studies with participants of both genders which had assessed BF% using P-US compared to the reference standard were selected. Publications up until May 31, 2022 were searched in the MEDLINE, COCHRANE, Science Direct, Web of Science, LILACS, SciELO, PEDro, SPORT Discus, CINAHL and SCOPUS databases. QUADAS-2 was used to assess the risk of bias in the validity studies and QAREL was used for the methodological quality of reliability studies. The JAMOVI software program synthesized the results, from which the Pearson Correlation Coefficient (r) or the square root of the Multiple Linear Regression Determination Coefficient (R2) were extracted for the validity studies, and the Mean of Errors of the Bland-Altman Test (ME) and the Confidence Interval (95%CI) with Upper and Lower Limits for the reliability studies. A total of 13 studies were included, generating 26 results for the quantitative synthesis, 14 for validity and 12 for reliability. Regarding the validity results, a strong correlation was identified between the equipment (r = 0.870 [0.845-0.895], P<0.001), with moderate and true heterogeneity (I2 = 53.47%, P = 0.003), presenting publication bias. A small effect size was identified regarding the reliability results, overestimating the results due to chance between the devices (ME = 0.207 [-0.798-1.212], P = 0.686), with low heterogeneity also due to chance (I2 = 19.44%, P = 0.253), with no publication bias. All of the evaluated studies showed some violation of the instruments, confirming the high risk of bias and the low methodological quality. There is concern with heterogeneity for the validity results explained by the subgroups' analysis. The P-US associated with anthropometric perimeters satisfactorily measures the BF% with samples greater than 100 participants, and males. The results in the reliability assessment show high agreement and high variability, greatly expanding the confidence interval, which should be viewed with reservations. This review received financial support from the Brazilian Air Force. The study was registered with PROSPERO under the number CRD42020166617.


Assuntos
Esportes , Humanos , Masculino , Feminino , Reprodutibilidade dos Testes , Ultrassonografia/métodos , Tecido Adiposo/diagnóstico por imagem , Brasil
17.
Stem Cell Res Ther ; 15(1): 37, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331803

RESUMO

Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell-cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell-cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.


Assuntos
Células-Tronco Mesenquimais , Dermatopatias , Adulto , Humanos , Tecido Adiposo , Células-Tronco Mesenquimais/metabolismo , Adipócitos , Pele , Dermatopatias/terapia , Dermatopatias/metabolismo
18.
Stem Cell Res Ther ; 15(1): 36, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331889

RESUMO

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Pericitos , Células Endoteliais/metabolismo , Tecido Adiposo/metabolismo , Apoptose , Células Cultivadas
19.
Medicine (Baltimore) ; 103(6): e37014, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335380

RESUMO

Coronary artery disease (CAD) is a predominant cardiovascular disorder, particularly in the aging population. The pathophysiology of atherosclerosis involves lipid deposition and inflammation of the arterial walls. With coronary computed tomography angiography offering insights into coronary anatomy and pathology, parameters such as pericoronary adipose tissue mean attenuation (PCATMA) have gained significance in the understanding of cardiac diseases. A retrospective study encompassing 130 patients with CAD was conducted to analyze 269 observation points. Coronary CT Angiography was employed, with specific attention paid to the measurement of PCATMA and a qualitative and quantitative assessment of plaques. Statistical analyses were performed using Statistical Package for the Social Sciences software (version 27.0), independent samples t test, one-way ANOVA, and multivariate logistic regression analysis. There was a notable correlation between PCATMA expression and severity of coronary artery calcification and stenosis. Patients with higher coronary artery calcification scores and more pronounced stenosis had elevated PCATMA values. Variances in PCATMA based on plaque type and degree of stenosis were significant (P < .05). Multivariate logistic regression revealed that plaque presence, type, and degree of stenosis were independent determinants of PCATMA expression. PCATMA expression is closely associated with CAD progression. As plaque calcification and arterial stenosis increase, there is a concomitant increase in PCATMA expression, potentially serving as a pivotal prognostic indicator.


Assuntos
Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Idoso , Angiografia por Tomografia Computadorizada/métodos , Estudos Retrospectivos , Constrição Patológica/complicações , Placa Aterosclerótica/patologia , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Tecido Adiposo/patologia , Vasos Coronários/patologia , Valor Preditivo dos Testes
20.
Skin Res Technol ; 30(2): e13601, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297988

RESUMO

RESULT: The review delves into the realm of reducing submental fat, presenting a comprehensive analysis of various lipolytic agents used in plastic surgery and dermatology. The introduction establishes the context by defining the key indicators of a youthful neck and emphasizing the significant influence of fat in the aging process, particularly in the submental area. The usage of aminophylline involves subcutaneous injections, facilitating fat breakdown by increasing cyclic adenosine monophosphate and inhibiting adenosine receptors. Hypotonic pharmacologic lipo-dissolution induces fat dissolution via injected compounds under pressure, while lipolytic lymphatic drainage employs hyaluronidase to reduce tissue viscosity, aiding fat circulation. Glycerophosphorylcholine containing choline alfoscerate claims to activate fat metabolism, whereas the utilization of phosphatidylcholine combined with deoxycholate lacks cosmetic approval due to safety concerns. Deoxycholic acid has FDA approval for submental fat reduction, yet its mechanisms remain incompletely understood. Understanding the complex anatomy and mechanisms of lipolytic agents is essential for safe and effective submental fat reduction, despite evolving practices and off-label utilization. Clinical guidelines and references support this discussion, offering insights for safer applications.


Assuntos
Tecido Adiposo , Técnicas Cosméticas , Humanos , Ácido Desoxicólico/farmacologia , Injeções Subcutâneas , Aminofilina/farmacologia , Gordura Subcutânea
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