Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.630
Filtrar
1.
Eur Rev Med Pharmacol Sci ; 28(4): 1439-1455, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436178

RESUMO

OBJECTIVE: Adipose tissue is the largest endocrine organ in the human body, and as its mass changes, the serum levels of the molecules it secretes also change. Visceral adipose tissue index (VAI) is a simple surrogate marker of visceral adipose tissue dysfunction. This study evaluated the effects of changes in fat mass on adipocytokine behavior and VAI in patients with anorexia nervosa (AN) and extreme obesity (EO). PATIENTS AND METHODS: The study group consisted of three subgroups: Group 1, patients with EO who were candidates for obesity surgery with BMI≥50 kg/m2 (n=20). Group 2, newly diagnosed patients with AN (n=12). Group 3 controls with BMI 20-25 kg/m2 (n=20). The AN and EO groups were followed until at least a 10% weight change before and after the intervention. RESULTS: Prior to the intervention, EO patients exhibited the lowest levels of apelin, omentin, and adiponectin, while AN patients demonstrated the highest levels of these markers. Leptin and IL-6 were elevated in EO and reduced in AN patients. After treatment, all adipokines and VAI increased in AN patients, and omentin, adiponectin, and IL-6 increased in EO patients, while apelin, leptin, and VAI decreased. The change in each adipocytokine (∆) was positively correlated with the other adipocytokines (p<0.050) and negatively correlated with metabolic and VAI changes (p<0.050). The regression analysis determined that the following variables were associated with the change in adipose tissue mass: Δapelin (OR: 1.061; p=0.028) and Δadiponectin (OR: 1.057; p=0.036). CONCLUSIONS: In individuals with pathological adipocyte mass, the change in adipocytokine levels in response to weight change is not as expected. The fact that these changes are not seen in the early period of the weight intervention treatment indicates that these patients have compensatory physiological mechanisms to protect them. In addition, using VAI instead of BMI, whose reliability is increasingly questioned because it does not reflect body fat mass, can be considered an alternative. However, there may be modeling errors in the early stages of weight change and in AN and EO patients where metabolic parameters reach extreme values. Therefore, it should be tested in studies where larger patient groups are followed for a more extended period.


Assuntos
Anorexia Nervosa , Obesidade Mórbida , Humanos , Leptina , Adipocinas , Apelina , Adiponectina , Interleucina-6 , Estudos Prospectivos , Reprodutibilidade dos Testes , Adipócitos
2.
Int J Mol Sci ; 25(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38473909

RESUMO

Mutations of the FBN1 gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down FBN1 in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction. Furthermore, we incubated the shFBN1 SMCs with Coenzyme Q10 (CoQ10) to assess whether restoring mitochondrial function can reverse the phenotypic transformation. The results showed that shFBN1 SMCs had decreased TFAM (mitochondrial transcription factor A), mtDNA levels and mitochondrial mass, lost their contractile capacity and had increased synthetic phenotype markers. Inhibiting the mitochondrial function of SMCs can decrease the expression of contractile markers and increase the expression of synthetic genes. Imposing mitochondrial stress causes a double-hit effect on the TFAM level, oxidative phosphorylation and phenotypic transformation of FBN1-knockdown SMCs while restoring mitochondrial metabolism with CoQ10 can rapidly reverse the synthetic phenotype. Our results suggest that mitochondria function is a potential therapeutic target for the phenotypic transformation of SMCs in MFS.


Assuntos
Síndrome de Marfan , Doenças Mitocondriais , Ubiquinona/análogos & derivados , Humanos , Síndrome de Marfan/genética , Fenótipo , Miócitos de Músculo Liso/metabolismo , Doenças Mitocondriais/metabolismo , Fibrilina-1/metabolismo , Adipocinas/metabolismo
3.
Physiol Res ; 73(1): 1-8, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466000

RESUMO

Periovarian adipose tissue (POAT) is a type of gonadal white adipose tissue that surrounds the ovary. POAT is a source of various bioactive molecules, such as adipokines, cytokines, chemokines, growth factors and hormones. Thereby it could influence crucial ovarian functions. Recent findings showed that removal of POAT affects folliculogenesis and steroidogenesis in the ovary. Furthermore, changes in the morphology and function of POAT were observed in women during menopause or polycystic ovary syndrome. Although the relationship between the body's energy status and fertility in females is generally well known, the contribution of POAT remains still elusive. Therefore, the objective of this review is summarizing the actual state of knowledge about POAT function in physiological and pathological processes within the ovary.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/metabolismo , Tecido Adiposo/metabolismo , Fertilidade , Adipocinas
4.
RMD Open ; 10(1)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519111

RESUMO

OBJECTIVE: In this post hoc analysis of a previously published study, we compared cytokines and adipokine levels in women and men with psoriatic arthritis (PsA) at baseline (BL) and 6 months (M6) following a weight loss intervention. METHODS: Patients with PsA (n=41) between 25 and 75 years of age, with body mass index (BMI)≥33 kg/m2 were included in a weight loss intervention with a very low energy diet (VLED) for 12 or 16 weeks depending on BL BMI<40 or ≥40 kg/m2. As controls (n=39), obese individuals, already planned for VLED treatment were recruited and matched for sex, age and weight to the patients with PsA. Cytokines and adipokines were measured at BL and M6. RESULTS: At BL, serum levels of interleukin (IL)-23, leptin and high molecular weight-adiponectin were higher in women with PsA compared with men, whereas serum levels of interferon (IFN)-γ, IL-12/IL-23 p40 and IL-13 were significantly lower in women. Serum IL-23 was significantly reduced at M6 compared with BL in women but not in men with PsA. In women with PsA, the reduction in IL-23 at M6, ∆IL-23, were positively correlated with ∆Disease Activity Score 28 C reactive protein (CRP) (Spearman's correlation (rS)=0.486, p=0.016), ∆CRP (rS=0.468, p=0.021), ∆leptin (rS=0.683, p<0.001) and negatively correlated with ∆total-adiponectin (rS=-0.433, p=0.035). Also in women, ∆Disease Activity in Psoriatic Arthritis was positively correlated with ∆tumour necrosis factor-α (rS=0.417, p=0.034), ∆IL-1ß (rS=0.550, p=0.034), ∆IFN-γ (rS=0.414, p=0.035) and ∆leptin (rS=0.410, p=0.038). None of these correlations were significant in men with PsA. CONCLUSIONS: Women and men with PsA differed with regard to serum levels of cytokines and adipokines before and after weight loss.


Assuntos
Adipocinas , Artrite Psoriásica , Humanos , Feminino , Masculino , Citocinas , Adiponectina , Caracteres Sexuais , Obesidade/complicações , Proteína C-Reativa , Redução de Peso , Interleucina-23
5.
Front Endocrinol (Lausanne) ; 15: 1336543, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516409

RESUMO

The prevalence of osteoporosis has been on the rise globally. With ageing populations, research has sought therapeutic solutions in novel areas. One such area is that of the adipokines. Current literature points to an important role for these chemical mediators in relation to bone metabolism. Well-established adipokines have been broadly reported upon. These include adiponectin and leptin. However, other novel adipokines such as visfatin, nesfatin-1, meteorin-like protein (Metrnl), apelin and lipocalin-2 are starting to be addressed pre-clinically and clinically. Adipokines hold pro-inflammatory and anti-inflammatory properties that influence the pathophysiology of various bone diseases. Omentin-1 and vaspin, two novel adipokines, share cardioprotective effects and play essential roles in bone metabolism. Studies have reported bone-protective effects of omentin-1, whilst others report negative associations between omentin-1 and bone mineral density. Lipocalin-2 is linked to poor bone microarchitecture in mice and is even suggested to mediate osteoporosis development from prolonged disuse. Nesfatin-1, an anorexigenic adipokine, has been known to preserve bone density. Animal studies have demonstrated that nesfatin-1 treatment limits bone loss and increases bone strength, suggesting exogenous use as a potential treatment for osteopenic disorders. Pre-clinical studies have shown adipokine apelin to have a role in bone metabolism, mediated by the enhancement of osteoblast genesis and the inhibition of programmed cell death. Although many investigations have reported conflicting findings, sufficient literature supports the notion that adipokines have a significant influence on the metabolism of bone. This review aims at highlighting the role of novel adipokines in osteoporosis while also discussing their potential for treating osteoporosis.


Assuntos
Osteoporose , Serpinas , Animais , Camundongos , Adipocinas/metabolismo , Apelina/metabolismo , Lipocalina-2 , Adiponectina/metabolismo , Osteoporose/tratamento farmacológico
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 271-277, 2024 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-38448013

RESUMO

OBJECTIVE: To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. METHODS: Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing. RESULTS: All of the six patients had presented with severe short stature (< 3s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c.5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c.5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c.5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c.5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c.5156G>T was rated as a pathogenic variant (PS2+PM1+PM2_Supporting +PM5+PP3). CONCLUSION: All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.


Assuntos
Doenças do Desenvolvimento Ósseo , Nanismo , Deformidades Congênitas dos Membros , Humanos , Feminino , Animais , Estudos Retrospectivos , Fenótipo , China , Fibrilina-1/genética , Adipocinas
7.
Gen Comp Endocrinol ; 349: 114466, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325528

RESUMO

Some evidence showed differences between layer and broiler embryo development. We recently showed that two adipokines, adiponectin and visfatin are expressed in the extra embryonic membranes and fluids. However, their role in the embryo development is unknown. Thus, our objectives were 1. to compare the expression of AdipoQ and its receptors AdipoR1 and AdipoR2 and visfatin in extra-embryonic annexes in broiler and layer breeders during the embryo development and 2. to investigate the role of two adipokines in embryo development in both broiler and layer breed after in ovo injection of blocking antibodies against chicken adiponectin or visfatin. We found that adiponectin, AdipoR1, AdipoR2 and visfatin were mainly more expressed in the allantoic that in amniotic membranes. In addition, these expressions increased according the stage of embryo development. We observed a higher expression in layer than in broiler of AdipoQ in allantoic membranes at ED14 and ED18, of AdipoR1 and AdipoR2 in both allantoic and amniotic membranes at ED7 and ED14 and of visfatin only in allantoic membrane from ED7 to ED18. AdipoQ and visfatin were absent in amniotic fluid at ED7 but present at ED14 or ED18 where higher concentrations were detected in layer than in broiler. Interestingly, we showed a strong positive correlation between Adipo and visfatin concentration in amniotic fluid and the body weight of embryo in both breeds. However, after in ovo injection of Adipo antibodies we did not observe any effect on the embryo mortality whereas injection of visfatin antibodies increased in a dose dependent manner the embryo mortality in both breeds. Taken together, Adipo and visfatin are higher expressed in layer than broiler in extra-embryonic membranes and amniotic fluid. Our data suggest also that visfatin could be a main regulator of embryo development.


Assuntos
Adiponectina , Nicotinamida Fosforribosiltransferase , Animais , Galinhas , Adipocinas , Desenvolvimento Embrionário
8.
BMC Med Genomics ; 17(1): 47, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317175

RESUMO

BACKGROUND: Mutations in fibrillin-1 (FBN1) are known to be associated with Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Most FBN1 mutations are missense or nonsense mutations. Traditional molecular genetic testing for the FBN1 gene, like Sanger sequencing, may miss disease-causing mutations in the gene's regulatory regions or non-coding sequences, as well as partial or complete gene deletions and duplications. METHODS: Next-generation sequencing, multiplex ligation-dependent probe amplification and gap PCR were conducted on two MFS patients to screen for disease-causing mutations. RESULTS: We identified two large deletions in FBN1 from two MFS patients. One patient had a 0.23 Mb deletion (NC_000015.9:g.48550506_48779360del) including 5'UTR-exon6 of FBN1. The other patient harbored a 1416 bp deletion (NC_000015.9:g.48410869_48412284del) affecting the last exon, exon 66, of the FBN1 gene. CONCLUSION: Our results expanded the number of large FBN1 deletions and highlighted the importance of screening for large deletions in FBN1 in clinical genetic testing, especially for those with the classic MFS phenotype.


Assuntos
Síndrome de Marfan , Reação em Cadeia da Polimerase Multiplex , Humanos , Testes Genéticos , Mutação , Síndrome de Marfan/genética , Síndrome de Marfan/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Fibrilina-1/genética , Adipocinas/genética
9.
Toxicon ; 240: 107640, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325757

RESUMO

The effects of dietary supplementation with Capsicum annuum fruit pericarp powder (CPP) and Capsicum annuum fruit seed powder (CSP) on the health and performance of broiler chickens exposed to aflatoxin B1 (AFB1) was investigated. Four dietary groups were established: CON (control), AFT (0.5 mg/kg AFB1), CPAF (0.5 g/kg CPP and 0.5 mg/kg AFB1), and CSAF (0.5 g/kg CSP and 0.5 mg/kg AFB1). The AFT group shows a significant (P < 0.05) reduction in the relative growth rate compared to CON, CPAF, and CSAF. In contrast, the latter two groups exhibit growth rates similar (P > 0.05) to CON. Additionally, immunoglobulin levels (IgG, IgM, and IgA) in the AFT group are significantly (P < 0.05) lower compared to the other treatment groups. Serum interleukin-6 levels in the CPAF and CSAF groups were similar (P > 0.05) to CON but higher (P < 0.05) than in AFT. Tumor necrosis factor-alpha levels were elevated (P < 0.05) in AFT compared to the other treatment groups. Interferon-gamma concentrations in AFT were significantly (P < 0.05) lower than in the other treatment groups. The liver histology reveals that the AFT treatment group has periportal hepatic inflammation. In contrast, the CPAF and CSAF treatment groups exhibit normal hepatic microanatomy. In conclusion, 0.5 g/kg CPAF dietary supplementation may help to ameliorate the adverse effects of AFB1 exposure on broiler chicken health, specifically the growth, immune parameters and liver histology.


Assuntos
Capsicum , Fator de Ativação de Plaquetas/análogos & derivados , Animais , Galinhas , Aflatoxina B1/toxicidade , Aflatoxina B1/análise , Pós/farmacologia , Citocinas , Adipocinas/farmacologia , Fígado , Suplementos Nutricionais , Imunoglobulinas , Carne , Ração Animal/análise
10.
J Physiol ; 602(5): 773-790, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38305477

RESUMO

Adipose tissue, as an endocrine organ, secretes several adipocyte-derived hormones named 'adipokines' that are implicated in regulating energy haemostasis. Substantial evidence shows that white adipose tissue-derived adipokines mediate the link between obesity-related exogenous factors (like diet and lifestyle) and various biological events (such as pre- and postmenopausal status) that have obesity consequences (cardiometabolic disorders). One of the critical aetiological factors for obesity-related diseases is the dysfunction of adipokine pathways. Acylation-stimulating protein (ASP) is an adipokine that stimulates triglyceride synthesis and storage in adipose tissue by enhancing glucose and fatty acid uptake. ASP acts via its receptor C5L2. The primary objective of this review is to address the existing gap in the literature regarding ASP by investigating its diverse responses and receptor interactions across multiple determinants of obesity. These determinants include diet composition, metabolic disorders, organ involvement, sex and sex hormone levels. Furthermore, this article explores the broader paradigm shift from solely focusing on adipose tissue mass, which contributes to obesity, to considering the broader implications of adipose tissue function. Additionally, we raise a critical question concerning the clinical relevance of the insights gained from this review, both in terms of potential therapeutic interventions targeting ASP and in the context of preventing obesity-related conditions, highlighting the potential of the ASP-C5L2 interaction as a pharmacological target. In conclusion, these findings validate that obesity is a low-grade inflammatory status with multiorgan involvement and sex differences, demonstrating dynamic interactions between immune and metabolic response determinants.


Assuntos
Adipócitos , Tecido Adiposo , Complemento C3a , Feminino , Humanos , Masculino , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Adipocinas/metabolismo
11.
Inflammopharmacology ; 32(1): 355-376, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38170330

RESUMO

BACKGROUND: Although a large number of trials have observed an anti-inflammatory property of acarbose, the currently available research remains controversial regarding its beneficial health effects. Hence, the purpose of this study was to examine the effect of acarbose on inflammatory cytokines and adipokines in adults. METHODS: PubMed, Web of Science, and Scopus were systematically searched until April 2023 using relevant keywords. The mean difference (MD) of any effect was calculated using a random-effects model. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated via the random-effects model. RESULTS: The current meta-analysis of data comprised a total of 19 RCTs. Meta-analysis showed that acarbose significantly decreased tumor necrosis factor-alpha (TNF-α) (weighted mean difference [WMD]) = - 4.16 pg/ml, 95% confidence interval (CI) - 6.58, - 1.74; P = 0.001) while increasing adiponectin (WMD = 0.79 ng/ml, 95% CI 0.02, 1.55; P = 0.044). However, the effects of acarbose on TNF-α concentrations were observed in studies with intervention doses ≥ 300 mg/d (WMD = - 4.09; 95% CI - 7.00, - 1.18; P = 0.006), and the adiponectin concentrations were significantly higher (WMD = 1.03 ng/ml, 95%CI 0.19, 1.87; P = 0.016) in studies in which the duration of intervention was less than 24 weeks. No significant effect was seen for C-reactive protein (CRP; P = 0.134), interleukin-6 (IL-6; P = 0.204), and leptin (P = 0.576). CONCLUSION: Acarbose had beneficial effects on reducing inflammation and increasing adiponectin. In this way, it may prevent the development of chronic diseases related to inflammation. However, more studies are needed.


Assuntos
Adipocinas , Citocinas , Adulto , Humanos , Acarbose/farmacologia , Acarbose/uso terapêutico , Adiponectina , Fator de Necrose Tumoral alfa , Ensaios Clínicos Controlados Aleatórios como Assunto , Interleucina-6 , Inflamação/tratamento farmacológico
12.
Diabetes ; 73(2): 169-177, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241508

RESUMO

Excessive adiposity in obesity is a significant risk factor for development of type 2 diabetes (T2D), nonalcoholic fatty liver disease, and other cardiometabolic diseases. An unhealthy expansion of adipose tissue (AT) results in reduced adipogenesis, increased adipocyte hypertrophy, adipocyte hypoxia, chronic low-grade inflammation, increased macrophage infiltration, and insulin resistance. This ultimately culminates in AT dysfunction characterized by decreased secretion of antidiabetic adipokines such as adiponectin and adipsin and increased secretion of proinflammatory prodiabetic adipokines including RBP4 and resistin. This imbalance in adipokine secretion alters the physiological state of AT communication with target organs including pancreatic ß-cells, heart, and liver. In the pancreatic ß-cells, adipokines are known to have a direct effect on insulin secretion, gene expression, cell death, and/or dedifferentiation. For instance, impaired secretion of adipsin, which promotes insulin secretion and ß-cell identity, results in ß-cell failure and T2D, thus presenting a potential druggable target to improve and/or preserve ß-cell function. The cardiac tissue is affected by both the classic white AT-secreted adipokines and the newly recognized brown AT (BAT)-secreted BATokines or lipokines that alter lipid deposition and ventricular function. In the liver, adipokines affect hepatic gluconeogenesis, lipid accumulation, and insulin sensitivity, underscoring the importance of adipose-liver communication in the pathogenesis of nonalcoholic fatty liver disease. In this perspective, we outline what is currently known about the effects of individual adipokines on pancreatic ß-cells, liver, and the heart.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adiposidade , Fator D do Complemento/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Tecido Adiposo/metabolismo , Adipocinas/metabolismo , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Inflamação/metabolismo , Lipídeos , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo
13.
Cells ; 13(2)2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38247865

RESUMO

Obesity is a growing pandemic with an increasing risk of inducing different cancer types, including breast cancer. Adipose tissue is proposed to be a major player in the initiation and progression of breast cancer in obese people. However, the mechanistic link between adipogenicity and tumorigenicity in breast tissues is poorly understood. We used in vitro and in vivo approaches to investigate the mechanistic relationship between obesity and the onset and progression of breast cancer. In obesity, adipose tissue expansion and remodeling are associated with increased inflammatory mediator's release and anti-inflammatory mediators' reduction.. In order to mimic the obesity micro-environment, we cultured cells in an enriched pro-inflammatory cytokine medium to which we added a low concentration of beneficial adipokines. Epithelial cells exposed to the obesity micro-environment were phenotypically transformed into mesenchymal-like cells, characterized by an increase in different mesenchymal markers and the acquisition of the major hallmarks of cancerous cells; these include sustained DNA damage, the activation of the ATR-Chk2 pathway, an increase in proliferation rate, cell invasion, and resistance to conventional chemotherapy. Transcriptomic analysis revealed that several genes, including RhoJ, CCL7, and MMP9, acted as potential major players in the observed phenomenon. The transcriptomics findings were confirmed in vitro using qRT-PCR and in vivo using high-fat-diet-fed mice. Our data suggests RhoJ as a potential novel molecular driver of tumor development in breast tissues and a mediator of cell resistance to conventional chemotherapy through PAK1 activation. These data propose that RhoJ is a potential target for therapeutic interventions in obese breast cancer patients.


Assuntos
Neoplasias da Mama , Obesidade , Proteínas rho de Ligação ao GTP , Animais , Feminino , Humanos , Camundongos , Adipocinas , Adiposidade , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Obesidade/complicações , Microambiente Tumoral , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
14.
Nutr Cancer ; 76(3): 262-270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38225859

RESUMO

BACKGROUND: Serum adipokines (leptin and adiponectin) are dysregulated before the onset of metabolic syndrome and hence may be useful biomarkers for screening of cardiometabolic late effects in childhood Acute Lymphoblastic Leukemia (cALL) survivors. METHODS: We compared serum adipokine levels between 40 cALL survivors (aged 10-18 years, >2 years from treatment completion) with similar controls. A multivariable logistic regression analysis was then done to assess the association of metabolic syndrome in cALL survivors with variables including adipokines and other metabolic parameters, demographic and treatment details, and Dual-energy X-ray absorptiometry scan-derived variables. RESULTS: Compared to controls, cALL survivors had a higher prevalence of metabolic syndrome (8/40 vs. 2/40, P = .044) and central obesity (11/40 vs. 4/40, P = 0.042). Median Serum Leptin (7.39 vs. 4.23 ng/ml, P = 0.207) levels and derived Leptin-Adiponectin Ratio (1.44 vs. 0.80, P = 0.598), were higher but not statistically different in our survivors compared to controls; Adiponectin levels were similar (6.07 vs. 5.01 µg/ml, P = 0.283). In the cALL survivors, overweight/obesity (odds ratio [OR] 21.9, P = 0.020) or higher Leptin levels (OR 1.11, P = 0.047), were independently associated with metabolic syndrome. CONCLUSIONS: Serum Leptin, independently predictive of metabolic syndrome in our cALL survivors, may be tested in larger studies to assess its utility in surveillance and initiation of early preventive measures.


Assuntos
Síndrome Metabólica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Leptina , Adipocinas , Adiponectina , Países em Desenvolvimento , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Obesidade/complicações , Sobreviventes , Biomarcadores
15.
J Clin Lab Anal ; 38(1-2): e25009, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38234087

RESUMO

BACKGROUND: Marfan syndrome (MFS), caused by pathogenic variants of FBN1 (fibrillin-1), is a systemic connective tissue disorder with variable phenotypes and treatment responsiveness depending on the variant. However, a significant number of individuals with MFS remain genetically unexplained. In this study, we report novel pathogenic intronic variants in FBN1 in two unrelated families with MFS. METHODS: We evaluated subjects with suspected MFS from two unrelated families using Sanger sequencing or multiplex ligation-dependent probe amplification of FBN1 and/or panel-based next-generation sequencing. As no pathogenic variants were identified, whole-genome sequencing was performed. Identified variants were analyzed by reverse transcription-PCR and targeted sequencing of FBN1 mRNA harvested from peripheral blood or skin fibroblasts obtained from affected probands. RESULTS: We found causative deep intronic variants, c.6163+1484A>T and c.5788+36C>A, in FBN1. The splicing analysis revealed an insertion of in-frame or out-of-frame intronic sequences of the FBN1 transcript predicted to alter function of calcium-binding epidermal growth factor protein domain. Family members carrying c.6163+1484A>T had high systemic scores including prominent skeletal features and aortic dissection with lesser aortic dilatation. Family members carrying c.5788+36C>A had more severe aortic root dilatation without aortic dissection. Both families had ectopia lentis. CONCLUSION: Variable penetrance of the phenotype and negative genetic testing in MFS families should raise the possibility of deep intronic FBN1 variants and the need for additional molecular studies. This study expands the mutation spectrum of FBN1 and points out the importance of intronic sequence analysis and the need for integrative functional studies in MFS diagnosis.


Assuntos
Doenças da Aorta , Dissecção Aórtica , Síndrome de Marfan , Humanos , Fibrilina-1/genética , Mutação/genética , Síndrome de Marfan/genética , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Testes Genéticos , Adipocinas/genética
16.
Pharmacol Rep ; 76(1): 112-126, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38236555

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of death globally. Multiple factors may contribute to the pathogenesis of CRC, including the abnormalities in the functioning of the endogenous opioid system (EOS) or adiponectin-related signaling. The aim of our study was to evaluate if differences in the expression of opioid receptors (ORs) influence the development of CRC and if modulation of adiponectin receptors using AdipoRon, a selective AdipoR1 receptor agonist, affects colorectal carcinogenesis. METHODS: Naltrexone, an opioid receptor antagonist, was injected intraperitoneally every second day for 2 weeks, at the dose of 1 mg/kg in healthy Balb/C mice to induce changes in ORs expression. CRC was induced by a single intraperitoneal injection of azoxymethane (AOM) and the addition of dextran sodium sulfate (DSS) into drinking water in three-week cycles. The development of CRC was assessed using macro- and microscopic scoring and molecular analysis (RT qPCR, ELISA) after 14 weeks. RESULTS: Naltrexone significantly increased the mRNA expression of Oprm1, Oprd1, and Oprk1 in the mouse colon and in the brain (non-significantly). The pretreatment of mice with naltrexone aggravated the course of CRC (as indicated by tumor area, colon thickness, and spleen weight). The level of circulatory adiponectin was lowered in mice with CRC and increased in the colon as compared with healthy mice. The ß-endorphin level was increased in the plasma of mice with CRC and decreased in the colon as compared to healthy mice. AdipoRon, AdipoR1 agonist, worsened the CRC development, and pretreatment with naltrexone enhanced this negative effect in mice. CRC did not affect the expression of the Adipor1 gene, but the Adipor1 level was increased in mice pretreated with naltrexone (AOM/DSS and healthy mice). AdipoRon did not influence the expression of opioid receptors at the mRNA level in the colon of mice with CRC. The mRNA expression of Ptgs2, Il6, Nos2, Il1b, Il18, Gsdmd, and Rela was increased in mice with CRC as compared to the healthy colon. AdipoRon significantly decreased mRNA expression of Ptgs2, Il6, Il1b, and Il18 as compared to CRC mice. CONCLUSION: EOS and adiponectin-related signaling may play a role in the pathogenesis of CRC and these systems may present some additivity during carcinogenesis.


Assuntos
Neoplasias Associadas a Colite , Colite , Neoplasias Colorretais , Camundongos , Animais , Interleucina-18 , Analgésicos Opioides/efeitos adversos , Interleucina-6 , Adipocinas , Naltrexona/farmacologia , Adiponectina/efeitos adversos , Ciclo-Oxigenase 2 , Carcinogênese , Azoximetano/toxicidade , Modelos Animais de Doenças , Receptores Opioides/genética , RNA Mensageiro , Sulfato de Dextrana , Neoplasias Colorretais/genética , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente
17.
Cell Biochem Funct ; 42(1): e3915, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269513

RESUMO

Three types of adipocytes, white, brown, and beige, regulate the systemic energy balance through the storage and expenditure of chemical energy. In addition, adipocytes produce various bioactive molecules known as adipokines. In contrast to white adipocyte-derived molecules, less information is available on the adipokines produced by brown adipocytes (batokine). This study explored the regulatory expression of interleukin (IL)-6 in cell culture studies. Norepinephrine or a nonselective ß-adrenergic receptor agonist increased the expression of IL-6 in primary brown adipocytes and HB2 brown adipocytes. Treatment with forskolin (Fsk), an activator of the cAMP-dependent protein kinase (PKA) pathway (downstream signaling of the ß-adrenergic receptor), efficiently stimulated IL-6 expression in brown adipocytes and myotubes. Phosphorylated CREB and phosphorylated p38 MAP kinase levels were increased in Fsk-treated brown adipocytes within 5 min. In contrast, a long-term (∼60 min and ∼4 h) treatment with Fsk was required for increase in STAT3 phosphorylation and C/EBPß expression, respectively. The PKA, p38 MAP kinase, STAT3, and C/EBPß pathways are required for the maximal IL-6 expression induced by Fsk, which were verified by use of various inhibitors of these signal pathways. Vitamin C enhanced Fsk-induced IL-6 expression through the extracellular signal-regulated kinase activity. The present study provides basic information on the regulatory expression of IL-6 in activated brown adipocytes.


Assuntos
Adipócitos Marrons , Proteína Quinase 14 Ativada por Mitógeno , Animais , Camundongos , Adipócitos Brancos , Adipocinas , Colforsina/farmacologia , Interleucina-6
18.
Am J Physiol Regul Integr Comp Physiol ; 326(3): R220-R229, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38223939

RESUMO

Adipose biopsy techniques are relatively undefined for exercise physiology research in individuals at or near normal weight. The purpose of this study was to compare the influence of two adipose biopsy techniques on tissue quality through measurements of adipocyte cell size, as well as mRNA and protein levels of select pro- and anti-inflammatory cytokines and adipokines. Thirteen participants (9 M, 4 W; 28 ± 4 yr; 27 ± 3 kg·m-2; V̇o2max: 3.3 ± 0.7 L·min-1) underwent subcutaneous adipose biopsies on either side of the umbilicus (incision: ∼8 cm lateral, sampling area: ∼5 cm lateral) using 1) a 6-mm Bergström biopsy needle and 2) a mini-liposuction approach with a 4-mm Mercedes biopsy needle that used prebiopsy tumescent delivery (∼30 mL 0.9% NaCl solution) into the sampling area (i.e., 'wet' technique). Tissue obtained was processed identically for analysis and both techniques returned high-quality tissue for histology (similar % intact adipocytes), mRNA (RNA integrity numbers >7.0), and protein. Adipocyte size was similar (P > 0.05) between both techniques (Bergström: 6,116 ± 1,652 µm2, 554-23,522 µm2; Mercedes: 6,517 ± 952 µm2, 926-21,969 µm2). There were also no differences (P > 0.05) between the two techniques for the measured cytokines (pro- and anti-inflammatory) and adipokines at the mRNA and protein levels. Adipocyte size was positively correlated with body mass index and body fat percentage, and negatively correlated with V̇o2max (P < 0.05). These results suggest both adipose biopsy techniques used in the current investigation are appropriate for histological, transcriptional, and translational level measurements in exercise physiology studies of nonobese women and men.NEW & NOTEWORTHY This study provides investigators with useful information related to adipose biopsy sampling approaches that can be used when planning studies that use measurements of adipose histology, as well as measurements at the mRNA and protein level. Adipose periumbilical sampling with the Bergström biopsy needle and the Mercedes wet mini-liposuction technique are both appropriate options for studies in exercise physiology and in nonobese individuals.


Assuntos
Adipocinas , Obesidade , Masculino , Humanos , Feminino , Obesidade/metabolismo , Biópsia , Citocinas , RNA Mensageiro/genética , Anti-Inflamatórios
19.
J Psychiatr Res ; 171: 163-170, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290234

RESUMO

BACKGROUND: Depressive disorder is a complex mental health condition in which the etiopathogenesis involves several factors. Suitable biomarkers for the development of depression have not yet been established. Alterations in cytokines are assumed to be involved in the pathophysiology of depressive disorder. Adipokines (also known as adipocytokines) are important factors that not only regulate the energy balance but also regulate the inflammatory and immune responses. This study investigated the serum levels of adiponectin, leptin, resistin, chemerin, and fetuin A and the possible role of these adipokines in depressive disorder. METHODS: We recruited a total of 73 patients diagnosed with recurrent depressive disorder (rDD) and 54 age- and sex-matched healthy controls (HCs). Serum adipocytokines were determined using ELISA kits (R&D, USA). The serum levels of the investigated molecules between depressive patients and HCs were compared, and diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating depressive patients from HCs. Correlations between the molecules and clinical variables were also evaluated. RESULTS: Patients with rDD had lower levels of serum adiponectin and chemerin and higher levels of serum leptin, resistin and fetuin A (p < 0.05) vs. controls. Moreover, ROC curve analysis showed that the area under the curve (AUC) values of above set of adipocytkines were >0.7, with a sensitivity and specificity over 80% in discriminating patients with rDD from HCs. CONCLUSIONS: These results suggest that circulating adipocytokies may hold promise as biomarkers for the diagnosis of rDD.


Assuntos
Adipocinas , Transtorno Depressivo , Humanos , Leptina , Resistina , Adiponectina , alfa-2-Glicoproteína-HS , Biomarcadores , Transtorno Depressivo/diagnóstico
20.
Obesity (Silver Spring) ; 32(3): 560-570, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38247441

RESUMO

OBJECTIVE: The study objective was to investigate the effect of cold exposure on the plasma levels of five potential human brown adipokines (chemokine ligand 14 [CXCL14], growth differentiation factor 15 [GDF15], fibroblast growth factor 21 [FGF21], interleukin 6 [IL6], and bone morphogenic protein 8b [BMP8b]) and to study whether such cold-induced effects are related to brown adipose tissue (BAT) volume, activity, or radiodensity in young humans. METHODS: Plasma levels of brown adipokines were measured before and 1 h and 2 h after starting an individualized cold exposure in 30 young adults (60% women, 21.9 ± 2.3 y; 24.9 ± 5.1 kg/m2 ). BAT volume, 18 F-fluorodeoxyglucose uptake, and radiodensity were assessed by a static positron emission tomography-computerized tomography scan after cold exposure. RESULTS: Cold exposure increased the concentration of CXCL14 (Δ2h = 0.58 ± 0.98 ng/mL; p = 0.007), GDF15 (Δ2h = 19.63 ± 46.2 pg/mL; p = 0.013), FGF21 (Δ2h = 33.72 ± 55.13 pg/mL; p = 0.003), and IL6 (Δ1h = 1.98 ± 3.56 pg/mL; p = 0.048) and reduced BMP8b (Δ2h = -37.12 ± 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Δ2h: ß = 0.456; R2 = 0.307; p = 0.001), but not with 18 F-fluorodeoxyglucose uptake or radiodensity. None of the changes in the other studied brown adipokines was related to BAT volume, activity, or radiodensity. CONCLUSIONS: Cold exposure modulates plasma levels of several potential brown adipokines in humans, whereas only cold-induced changes in FGF21 levels are associated with BAT volume. These findings suggest that human BAT might contribute to the circulatory pool of FGF21.


Assuntos
Adipocinas , Tecido Adiposo Marrom , Adulto Jovem , Humanos , Feminino , Masculino , Adipocinas/metabolismo , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Interleucina-6/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Fluordesoxiglucose F18/metabolismo , Temperatura Baixa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...