Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.153
Filtrar
1.
Gene ; 764: 145100, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32877748

RESUMO

Adipocyte differentiation is an essential part of adipose tissue development, and is closely related to obesity and obesity-related diseases. In this study, we found that the expression of PPARγ, RUVBL2 and Adiponectin were concurrently obviously increased in the 5th-7th day of 3T3-L1 cell differentiation. PPARγ overexpression or the PPARγ activator facilitated Adiponectin trafficking and secretion and upregulated RUVBL2 expression as well as AS160 phosphorylation during adipogenic differentiation of 3T3-L1 cells. Consistently RUVBL2 overexpression also enhanced the polymerization and secretion of Adiponectin, in contrast, RUVBL2 knockdown reduced Adiponectin secretion. Further, PPARγ significantly enhanced RUVBL2 promoter activity and transcription. The progressive deletions and mutations of RUVBL2 promoter for PPARγ binding sites suggested that the PPARγ binding motif situated at -804/-781 bp is an essential component required for RUVBL2 promoter activity. Chromatin immunoprecipitation (ChIP) assays determined that PPARγ can directly interact with the RUVBL2 promoter DNA. Taken together, these data suggest that PPARγ promotes the expression, polymerization and secretion of Adiponectin by activating RUVBL2 transcriptionally, which accelerates 3T3-L1 cell differentiation.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Adipócitos/fisiologia , Adipogenia/genética , Adiponectina/metabolismo , DNA Helicases/genética , PPAR gama/metabolismo , Células 3T3-L1 , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Animais , Sítios de Ligação/genética , Diferenciação Celular/genética , Imunoprecipitação da Cromatina , Clonagem Molecular , DNA Helicases/metabolismo , Camundongos , Mutação , Regiões Promotoras Genéticas/genética , Multimerização Proteica/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ativação Transcricional , Regulação para Cima
2.
Gene ; 771: 145380, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33359123

RESUMO

Adiponectin is an important hormone that regulates systemic metabolism, and it has been reported that globular adiponectin promotes myogenic differentiation. However, the mechanisms by which adiponectin promotes myogenic differentiation is not fully understood. In the present study, we show that adiponectin and its receptor 1 are significantly up-regulated during myogenic differentiation and that adiponectin increased the expression level of a core myogenic regulator, Mef2C, which is required for the effects of adiponectin on promoting myogenic differentiation. A transcriptional inhibitor of Mef2C, HDAC9, was down-regulated by adiponectin. In turn, Mef2C overexpression up-regulates adiponectin and its receptor, AdipoR1, to increase myogenic differentiation. We showed that mechanistically, Mef2C directly binds to AdipoR1 promoter to transcriptionally up-regulate AdipoR1 expression, which is required for the effects of Mef2C overexpression on myogenic differentiation. Thus, adiponectin/AdipoR1 and Mef2c form a positive feedback loop to promote myogenic differentiation.


Assuntos
Adiponectina/metabolismo , Receptores de Adiponectina/genética , Regulação para Cima , Animais , Diferenciação Celular , Linhagem Celular , Retroalimentação Fisiológica , Histona Desacetilases/metabolismo , Fatores de Transcrição MEF2/metabolismo , Camundongos , Desenvolvimento Muscular , Células NIH 3T3 , Cultura Primária de Células , Regiões Promotoras Genéticas , Receptores de Adiponectina/metabolismo , Proteínas Repressoras/metabolismo
3.
PLoS Genet ; 16(9): e1009019, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32915782

RESUMO

Loci identified in genome-wide association studies (GWAS) can include multiple distinct association signals. We sought to identify the molecular basis of multiple association signals for adiponectin, a hormone involved in glucose regulation secreted almost exclusively from adipose tissue, identified in the Metabolic Syndrome in Men (METSIM) study. With GWAS data for 9,262 men, four loci were significantly associated with adiponectin: ADIPOQ, CDH13, IRS1, and PBRM1. We performed stepwise conditional analyses to identify distinct association signals, a subset of which are also nearly independent (lead variant pairwise r2<0.01). Two loci exhibited allelic heterogeneity, ADIPOQ and CDH13. Of seven association signals at the ADIPOQ locus, two signals colocalized with adipose tissue expression quantitative trait loci (eQTLs) for three transcripts: trait-increasing alleles at one signal were associated with increased ADIPOQ and LINC02043, while trait-increasing alleles at the other signal were associated with decreased ADIPOQ-AS1. In reporter assays, adiponectin-increasing alleles at two signals showed corresponding directions of effect on transcriptional activity. Putative mechanisms for the seven ADIPOQ signals include a missense variant (ADIPOQ G90S), a splice variant, a promoter variant, and four enhancer variants. Of two association signals at the CDH13 locus, the first signal consisted of promoter variants, including the lead adipose tissue eQTL variant for CDH13, while a second signal included a distal intron 1 enhancer variant that showed ~2-fold allelic differences in transcriptional reporter activity. Fine-mapping and experimental validation demonstrated that multiple, distinct association signals at these loci can influence multiple transcripts through multiple molecular mechanisms.


Assuntos
Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Alelos , Caderinas/genética , Caderinas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Frequência do Gene/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Síndrome Metabólica/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Sequências Reguladoras de Ácido Nucleico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
Einstein (Sao Paulo) ; 18: eRW5160, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32876087

RESUMO

Adiponectin, among other diverse adipokines, is produced in greater quantity and has an effect on the adipose tissue and other tissues in the body. Adiponectin plays three main roles: regulatory metabolic and sensitizing function of insulin in the liver and muscles; it acts as an anti-inflammatory cytokine and in vascular protection, besides important cardiac protection in the presence of ischemia-reperfusion syndrome. Since many situations resulting from traumatic accidents or pathologies are due to cell damage caused by ischemia-reperfusion syndrome, it is relevant to study new therapeutic alternatives that will contribute to reducing these lesions. The objective of this study is to carry out a literature review on the role of adiponectin in ischemia-reperfusion syndrome.


Assuntos
Adiponectina/metabolismo , Isquemia/metabolismo , Traumatismo por Reperfusão , Tecido Adiposo , Citocinas , Humanos , Síndrome Metabólica
5.
Am J Physiol Renal Physiol ; 319(3): F469-F475, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32744085

RESUMO

A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's (B&K's) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K's mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24-h pH via leptin (P = 0.01) and adiponectin (P = 0.03) to be significant, with a trend for sICAM-1 (P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Rim/metabolismo , Leptina/metabolismo , Adiponectina/sangue , Adiponectina/genética , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Leptina/sangue , Leptina/genética , Masculino , Urinálise , Adulto Jovem
6.
Life Sci ; 259: 118270, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32814067

RESUMO

AIMS: Partial PPARγ agonists attracted substantially heightened interest as safer thiazolidinediones alternatives. On the other hand, Wnt/ß-catenin antagonists have been highlighted as promising strategy for type 2 diabetes management via up-regulating PPARγ gene expression. We aimed at synthesizing novel partial PPARγ agonists with ß-catenin inhibitory activity which could enhance insulin sensitivity and avoid the side effects of full PPARγ agonists. MAIN METHODS: We synthesized novel series of α-phthlimido-o-toluoyl-2-aminothiazoles hybrids for evaluating their antidiabetic activity and discovering its mechanistic pathway. We assessed effect of the new hybrids on PPARγ activation using a luciferase reporter assay system. Moreover, intracellular triglyceride levels, gene levels of c/EBPα, PPARγ and PPARγ targets including GLUT4, adiponectin, aP2 were measured in 3T3-L1 cells. Uptake of 2-DOG together with PPARγ and ß-catenin protein levels were evaluated in 3T3-L1cells. In addition, molecular docking studies with PPARγ LBD, physicochemical properties and structure activity relationship of the novel hybrids were also studied. KEY FINDINGS: Three of the synthesized hybrids showed partial PPARγ agonistic activity and distinct PPARγ binding pattern. These compounds modulated PPARγ gene expression and PPARγ target genes; and increased glucose uptake in 3T3-L1 and slightly induced adipogenesis compared to rosiglitazone. Moreover, these compounds reduced ß-catenin protein level which reflected in increased both PPARγ gene and protein levels that leads to improved insulin sensitivity and increased GLUT4 and adiponectin gene expression. SIGNIFICANCE: Our synthesized compounds act as novel partial PPARγ agonists and ß-catenin inhibitors that have potent insulin sensitizing activity and mitigate the lipogenic side effects of TZDs.


Assuntos
Resistência à Insulina/fisiologia , Ftalimidas/farmacologia , Tiazóis/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Adiponectina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Insulina/metabolismo , Camundongos , Simulação de Acoplamento Molecular , PPAR gama/agonistas , PPAR gama/metabolismo , Rosiglitazona/farmacologia , Tiazolidinedionas/farmacologia , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
7.
Orv Hetil ; 161(35): 1466-1474, 2020 08.
Artigo em Húngaro | MEDLINE | ID: mdl-32822325

RESUMO

INTRODUCTION: Health is an important motivation for the consumption of both organic and functional foods. Organic food contains fewer pesticide residues and statistically more selected health-related compounds such as polyphenols in plant products and polyunsaturated fatty acids in milk and meat products. Recent studies suggest that the gut-liver axis plays an important role in the pathogenesis of non-alcoholic fatty liver disease, so probiotics could be a therapeutic tool. Comparing the health effects of yoghurt from organic origin with so-called conventional yoghurt is difficult, because there is no biomarker that would signal the difference with good specificity and sensitivity. AIM: The aim of this study was to investigate numerous biomarkers to evaluate the difference between yoghurt from conventional and organic origin and their health effects in NAFLD. PATIENTS AND METHOD: We performed a prospective, cohort study consisting of 37 (age = 51.73 ± 11.82, male = 21, female = 16) patients with NAFLD at the 2nd Department of Internal Medicine of the Semmelweis University, Budapest. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. The patients were examined also with shear wave elastography to evaluate the hepatic fibrosis stage. We divided the patients randomly into two groups. The patients consumed individually daily 300 grams of yoghurt from organic (n = 21) or conventional (n = 16) origin for 8 weeks. We collected 37 routine laboratory data, measured 4 cytokines, 3 markers of the redox-homeostasis and 14 body composition values before, after, and 12 weeks after the yoghurt consumption. RESULTS: We found a mild elevation of vitamin D and a minimal reduction of LDL after the yoghurt consumption, but in the other 35 routine laboratory data there was no statistical difference. Adiponectin and leptin levels were elevated after the yoghurt consumption in the "conventional group". In contrast, we found significant decrease of adiponectin levels in the "organic group" after the treatment. Only the adiponectin tendency was different in the two groups. The induced free radical content was also statistically lower after the yoghurt consumption. In the body composition measurements, there were no significant differences. CONCLUSION: These data suggest that adiponectin could be a possible biomarker to evaluate the effectiveness of probiotic treatment in non-alcoholic fatty liver disease. Our work can serve as a basis for future studies investigating relationships between organic yoghurt consumption and health outcomes. Orv Hetil. 2020; 161(35): 1466-1474.


Assuntos
Adiponectina/metabolismo , Composição Corporal/fisiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Probióticos/farmacologia , Iogurte/microbiologia , Estudos de Coortes , Técnicas de Imagem por Elasticidade , Alimentos Orgânicos , Humanos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Probióticos/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento
8.
PLoS One ; 15(8): e0237095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756599

RESUMO

Regular exercise is an effective strategy that is used to prevent and treat obesity as well as type 2 diabetes. Exercise-induced myokine secretion is considered a mechanism that coordinates communication between muscles and other organs. In order to examine the possibility of novel communications from muscle to adipose tissue mediated by myokines, we treated 3T3-L1 adipocytes with C2C12 myotube electrical pulse stimulation-conditioned media (EPS-CM), using a C2C12 myotube contraction system stimulated by an electrical pulse. Continuous treatment with myotube EPS-CM promoted adipogenesis of 3T3-L1 pre-adipocytes via the upregulation of the peroxisome proliferator-activated receptor-gamma (PPARγ) 2 and PPARγ-regulated gene expression. Furthermore, our results revealed that myotube EPS-CM induces lipolysis and secretion of adiponectin in mature adipocytes. EPS-CM obtained from a C2C12 myoblast culture did not induce such changes in these genes, suggesting that contraction-induced myokine(s) secretion occurs particularly in differentiated myotubes. Thus, contraction-induced secretion of myokine(s) promotes adipogenesis and lipid metabolism in 3T3-L1 adipocytes. These findings suggest the possibility that skeletal muscle communicates to adipose tissues during exercise, probably by the intermediary of unidentified myokines.


Assuntos
Adipócitos/citologia , Diferenciação Celular , Lipólise , Fibras Musculares Esqueléticas/metabolismo , Células 3T3 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia , Adiponectina/metabolismo , Animais , Comunicação Celular , Meios de Cultivo Condicionados/farmacologia , Camundongos , PPAR gama/metabolismo
9.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(6): 374-382, jun.-jul. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-193362

RESUMO

BACKGROUND: The role of ADIPOQ gene rs266729 variants on weight loss after a dietary intervention are still unclear. OBJECTIVE: To analyze the effects of the ADIPOQ gene rs266729 variant n weight loss, cardiovascular risk factors, and adiponectin levels after two hypocaloric diets with different dietary fatty profiles. DESIGN: A population of 362 obese patients was enrolled in a randomized clinical trial with two diets (Diet M, monounsaturated fat-enriched diet, and Diet P, polyunsaturated-fat enriched diet). Anthropometric measurements, an assessment of nutritional intake, and biochemical tests were performed at baseline and after 12 weeks. RESULTS: Weight loss was similar with both diets. After Diet M, only subjects with CC genotype showed significant improvements in total cholesterol (CC vs. CG ± GG) -9.0 ±1.1 mU/L vs. -4.5 ± 2.4 mg/dL, p = 0.01), LDL cholesterol (-6.0 ± 1.1 mg/dL vs. -3.0 ± 0.9 mg/dL, p = 0.03), glucose (-4.7 ± 1.1 mg/dL vs. -0.6 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.6 ±1.0 mU/L vs. -0.7 ± 0.3 mU/L, p = 0.02) and in HOMA-IR (-0.5 ± 0.2 units vs. -0.2 ± 0.4 units, p = 0.03). The same improvement was reported after Diet P in all parameters, including total cholesterol (CC vs. CG±GG) (-8.0 ± 1.2mU/L vs. -2.1 ± 1.4 mg/dL, p = 0.02), LDL cholesterol (-7.3 ± 1.2 mg/dL vs. -2.1 ± 0.8 mg/dL, p = 0.02), glucose (-3.2 ± 0.1mg/dL vs. -0.2 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.5 ± 1.0 mU/L vs. -1 ± 0.6 mU/L, p = 0.02) and HOMA-IR (-0.5 ± 0.1 units vs. −0.3 ± 0.4 units, p = 0.02). Only subjects with CC genotype showed significant increases in adiponectin levels after both diets: (Diet M: 10.3 ± 2.0 ng/dL vs. Diet P: 9.3 ± 2.9 ng/dL, p = 0.43). CONCLUSION: The CC genotype of ADIPOQ gene rs266729 variant is associated to increased adiponectin levels and decreases in LDL cholesterol, glucose, insulin, and HOMA-IR levels after weight loss


ANTECEDENTES: El papel de las variantes del gen ADIPOQ en la pérdida de peso después de una intervención dietética sigue sin estar claro. OBJETIVO: Nuestro objetivo fue analizar los efectos de la variante rs266729 del gen ADIPOQ sobre la pérdida de peso, los factores de riesgo cardiovascular y los niveles de adiponectina después de 2 dietas hipocalóricas con diferentes perfiles de grasas en la dieta. DISEÑO: Una población de 362 pacientes obesos se incluyeron en un ensayo clínico aleatorizado con 2 dietas (dieta M: dieta enriquecida con grasas monoinsaturadas y dieta P: dieta enriquecida con grasas poliinsaturadas). Antes y tras 12 semanas, se realizó una evaluación antropométrica, evaluación de la ingesta nutricional y un análisis bioquímico. RESULTADOS: La pérdida de peso fue similar con ambas dietas. Después de la dieta M, solo los sujetos con genotipo CC mostraron una mejoría significativa en el colesterol total (CC vs. CG±GG) (-9,0 ± 1,1 mU/l vs. - 4,5 ± 2,4 mg/dl; p = 0,01), colesterol LDL (-6,0 ± 1,1 mg/dl vs. - 3,0 ± 0,9 mg/dl; p = 0,03), glucosa (-4,7 ± 1,1 mg/dl vs. -0,6 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,6 ± 1,0 mU/l vs. -0,7± 0,3 mU/l; p = 0,02) y HOMA-IR (- 0,5 ± 0,2 unidades vs. -0,2 ± 0,4 unidades; p = 0,03). La misma mejora en todos los parámetros se informó después de la dieta P; niveles de colesterol total (CC vs. CG ± GG) (-8,0 ± 1,2 mU/l vs. -2,1 ± 1,4 mg/dl; p = 0,02), colesterol LDL (-7,3 ± 1,2 mg/dl vs. -2,1 ±0,8 mg/dl; p = 0,02), glucosa (-3,2 ± 0,1 mg/dl vs. -0,2 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,5 ±1,0 mU/l vs. -1 ±0,6 mU/l; p = 0,02) y HOMA-IR (-0,5 ± 0,1 unidades vs. -0,3 ± 0,4 unidades; p = 0,02). Solo los sujetos con genotipo CC mostraron un aumento significativo de los niveles de adiponectina después de ambas dietas: (dieta M: 10,3 ± 2,0 ng/dl vs. dieta P: 9,3 ± 2,9 ng/dl; p = 0,43). CONCLUSIÓN: El genotipo CC de la variante rs266729 del gen ADIPOQ se asocia con aumentos en los niveles de adiponectina y disminución del colesterol LDL, glucosa, insulina y HOMA-IR tras la pérdida de peso


Assuntos
Humanos , Ácidos Graxos/sangue , Adiponectina/genética , Dieta Redutora/métodos , Perda de Peso , Gorduras na Dieta/uso terapêutico , Adiponectina/sangue , Obesidade/dietoterapia , Antropometria , LDL-Colesterol , Genótipo , Estudos Prospectivos , Adiponectina/metabolismo , Receptores de Adipocina/sangue , Análise de Variância
10.
Proc Natl Acad Sci U S A ; 117(29): 17381-17388, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32632018

RESUMO

Adiponectin (Acrp30) is an adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Although its effects are conventionally attributed to binding Adipor1/2 and T-cadherin, its abundance in circulation, role in ceramide metabolism, and homology to C1q suggest an overlooked role as a lipid-binding protein, possibly generalizable to other C1q/TNF-related proteins (CTRPs) and C1q family members. To investigate this, adiponectin, representative family members, and variants were expressed in Expi293 cells and tested for binding to lipids in liposomes using density centrifugation. Binding to physiological lipids were also analyzed using gradient ultracentrifugation, liquid chromatography-mass spectrometry, and shotgun lipidomics. Interestingly, adiponectin selectively bound several anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide-1-phosphate, glucosylceramide, and sulfatide, via the C1q domain in an oligomerization-dependent fashion. Binding to lipids was observed in liposomes, low-density lipoproteins, cell membranes, and plasma. Other CTRPs and C1q family members (Cbln1, CTRP1, CTRP5, and CTRP13) also bound similar lipids. These findings suggest that adiponectin and CTRPs function not only as hormones, but also as lipid opsonins, as may other C1q family proteins.


Assuntos
Adiponectina/metabolismo , Complemento C1q/metabolismo , Fosfolipídeos/metabolismo , Esfingolipídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adipocinas/metabolismo , Adiponectina/genética , Animais , Ânions , Membrana Celular , LDL-Colesterol , Humanos , Metabolismo dos Lipídeos , Lipidômica , Lipoproteínas/metabolismo , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Opsonizantes/metabolismo , Plasma
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(6): 555-560, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32696747

RESUMO

Adiponectin (APN), an important adipokine secreted by adipocytes, is known to play primary roles in the regulation of liver glucose homeostasis and lipid metabolism. APN has been demonstrated to be associated with various chronic liver diseases. However, the role of APN in the development of chronic hepatitis B virus (HBV) infection is still controversial. Herein, we aimed to summarize the recent findings regarding the role of APN in chronic HBV infection and update the current comprehensive knowledge regarding usefulness of APN as a diagnosis marker in liver fibrosis/cirrhosis. APN level in patients with chronic HBV infection was significantly higher than that in healthy controls, and increased in advanced liver fibrosis patients. The feasibility of APN as a diagnostic marker of liver fibrosis need further study. But it might be a biomarker for predicting the progression of HBV-related cirrhosis.


Assuntos
Adiponectina/metabolismo , Hepatite B Crônica , Fibrose , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática
12.
Arch Biochem Biophys ; 691: 108488, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32692982

RESUMO

Obesity is a metabolic disorder characterized by excess adipose tissue, macrophages infiltration, and inflammation which in turn lead to insulin-resistance. Epidemiological evidences reported that anthocyanins possess not only high antioxidant and antiinflammatory activities, but also improve metabolic complications associated with obesity. The aim of this work was to evaluate the in vitro beneficial effects of cyanidin-3-O-glucoside (C3G) in counteracting inflammation and insulin-resistance in 3T3-L1 hypertrophic adipocytes exposed to palmitic acid (PA). In the present study murine 3T3-L1 adipocytes were pretreated with C3G for 24 h and then exposed to palmitic acid (PA) for 24 h. Real-time PCR, western blotting analysis and Oil Red O staining were applied for investigating the mechanism involved in adipocytes dysfunction. C3G pretreatment reduced lipid accumulation, PPARγ pathway and NF-κB pathway induced by PA in murine adipocytes. In addition, our data demonstrated that PA reduced insulin signaling via IRS-1 Ser307phosphorylation while C3G dose-dependently improved insulin sensitivity restoring IRS-1/PI3K/Akt pathway. Furthermore, C3G improved adiponectin mRNA levels altered by PA in 3T3-L1 murine and SGBS human adipocytes. Herein reported data demonstrate that C3G ameliorated adipose tissue dysfunction, thus suggesting new potential roles for this compound of nutritional interest in the prevention of pathological conditions linked to obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Antocianinas/farmacologia , Glucosídeos/farmacologia , Inflamação/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Adiponectina/metabolismo , Animais , Proteínas de Ligação a Ácido Graxo/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Humanos , Resistência à Insulina/fisiologia , Camundongos , NF-kappa B/metabolismo , PPAR gama/metabolismo , Ácido Palmítico/farmacologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-32635165

RESUMO

The aim of the study was to determine the relationships between maternal smoking, total adiponectin, high molecular weight adiponectin (HMW adiponectin), selected somatomedins, and the birth weight of newborns. A total of 78 women with a healthy, singleton pregnancy, 41 active smokers and 37 non-smokers, and their offspring were studied. Total and HMW adiponectin, insulin-like growth factor I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) and 2 (IGFBP-2) were determined in maternal and cord blood by enzyme-link immunosorbent assay. Serum levels of total and HMW adiponectin were lower in smokers compared to the tobacco abstinent in both the mothers (p = 0.013; p = 0.006) and the infants (p = 0.001; p = 0.047). In smoking women and their children, serum concentrations of IGF-I were significantly lower (p = 0.014; p = 0.042), IGFBP-1 significantly higher (p = 0.009; p = 0.039), and IGFBP-2 did not differ from that observed in the non-smoking group. In multivariate analysis performed on the whole group of mothers, the highest impact of serum cotinine and IGFBP-2 levels were indicated for adiponectin and cotinine and the number of cigarettes/day for HMW adiponectin concentration. In correlation analysis estimated separately for smokers and non-smokers, neonatal birth weight was positively associated with total and HMW adiponectin concentrations in umbilical cord blood. Birth weight was also inversely associated with IGFBP-1 and positively correlated with IGF-I levels in maternal serum as well as in cord blood (r = -0.317, p = 0.005; r = -0.294, p = 0.004; r = 0.245, p = 0.031; r = 0.271, p = 0.009, respectively). The present study showed the levels of total and HMW adiponectin in umbilical cord blood may have a significant effect on fetal development. Both IGF-I and IGFBP-1 concentrations also play an essential role in fetal growth, which is an important predictor of birth weight. Cigarette smoking during pregnancy negatively affected adiponectin and the insulin growth factor profile in the serum of women and the cord blood and may be the reason for the lower birth weight of the smokers newborns compared with the nonsmokers offspring.


Assuntos
Adiponectina/metabolismo , Peso ao Nascer , Criança , Feminino , Sangue Fetal , Humanos , Lactente , Recém-Nascido , Fator de Crescimento Insulin-Like I , Masculino , Peso Molecular , Mães , Gravidez , Cuidado Pré-Natal
14.
Anticancer Res ; 40(7): 3751-3757, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620614

RESUMO

BACKGROUND/AIM: Colorectal cancer is frequently associated with metabolic diseases. Adiponectin (APN) is an insulin-sensitizing adipokine circulating as low molecular weight (LMW), medium molecular weight (MMW) and high molecular weight (HMW) oligomers; the latter are the most bio-active oligomers. APN, through AdipoR1, AdipoR2 and T-cadherin receptors, regulates inflammation, and proliferation. Considering the anti-proliferative and anti-inflammatory properties of APN, we investigated the involvement of the "APN system" in colorectal cancer. MATERIALS AND METHODS: A total of 44 colorectal cancer patients and 51 healthy controls were recruited. We analysed APN and HMW oligomers in sera, AdipoR1, AdipoR2 and T-cadherin expression in non-cancerous and cancerous colon tissues. RESULTS: we found statistically lower levels of APN in patients compared to controls, with a specific decrease of HMW oligomers. Importantly, APN correlated to cancer grade. AdipoR1 was found overexpressed in cancerous compared to non-cancerous tissues while AdipoR2 and T-cadherin were down-regulated. CONCLUSION: The deregulated expression of the "APN system" in colorectal cancer with a specific correlation to tumor grade suggests APN as a promising biomarker in colorectal cancer.


Assuntos
Adiponectina/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Estudos Transversais , Regulação para Baixo/fisiologia , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos
15.
Chem Biol Interact ; 327: 109176, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32534989

RESUMO

Alcoholic liver disease (ALD) is a progressively aggravated liver disease with high incidence in alcoholics. Ethanol-induced fat accumulation and the subsequent lipopolysaccharide (LPS)-driven inflammation bring liver from reversible steatosis, to irreversible hepatitis, fibrosis, cirrhosis, and even hepatocellular carcinoma. Peroxisome proliferator-activated receptor α (PPARα) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and plays pivotal roles in the regulation of fatty acid homeostasis as well as the inflammation control in the liver. It has been well documented that PPARα activity and/or expression are downregulated in liver of mice exposed to ethanol, which is thought to be one of the prime contributors to ethanol-induced steatosis, hepatitis and fibrosis. This article summarizes the current evidences from in vitro and animal models for the critical roles of PPARα in the onset and progression of ALD. Importantly, it should be noted that the expression of PPARα in human liver is reported to be similar to that in mice, and PPARα expression is downregulated in the liver of patients with nonalcoholic fatty liver disease (NAFLD), a disease sharing many similarities with ALD. Therefore, clinical trials investigating the expression of PPARα in the liver of ALD patients and the efficacy of strong PPARα agonists for the prevention and treatment of ALD are warranted.


Assuntos
Fígado Gorduroso Alcoólico/etiologia , PPAR alfa/metabolismo , Adiponectina/metabolismo , Animais , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Regulação para Baixo , Etanol , Fígado Gorduroso Alcoólico/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/etiologia , Inflamação/metabolismo , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , PPAR alfa/agonistas , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
16.
Int J Mol Sci ; 21(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32354030

RESUMO

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.


Assuntos
Antioxidantes/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Dieta , Suplementos Nutricionais , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Adiponectina/metabolismo , Ácido Ascórbico/administração & dosagem , Infecções por Coronavirus/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Flavonoides/administração & dosagem , Humanos , Interleucina-6/imunologia , Interleucina-6/metabolismo , Pneumopatias/imunologia , Pneumopatias/metabolismo , Pneumopatias/terapia , Pandemias , Pneumonia Viral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Invest Ophthalmol Vis Sci ; 61(5): 12, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32396633

RESUMO

Purpose: Adiponectin is an insulin-sensitizing and anticarcinogenic hormone that is encoded by a gene on chromosome 3. Here, we analyzed the expression of adiponectin and its receptor Adipor1 in primary uveal melanoma (UM) with regard to the monosomy-3 status and clinical factors, as well as the physiological response of UM cells to adiponectin. Methods: Immunohistochemistry was performed on the primary UM of 34 patients. Circulating melanoma cells (CMC) were isolated by immunomagnetic enrichment. Monosomy-3 was evaluated by Immuno-FISH. Gene expression was analyzed using the RNAseq data of The Cancer Genome Atlas study. Cultures of choroidal melanocytes and UM were established from the samples of two patients. The proliferative potential of the UM cell lines Mel-270 and OMM-2.5 was determined by immunocytochemistry, immunoblotting, cell cycle analysis, nucleolar staining, and adenosine triphosphate (ATP) levels. Results: UM with monosomy-3 exhibited a lower immunoreactivity for adiponectin and Adipor1, which was associated with monosomy-3-positive CMC and the development of extraocular growth or metastases. Both proteins were more abundant in the irradiated tumors and present in the cultured cells. Gene expression profile indicated the impairment of adiponectin-mediated signaling in the monosomy-3 tumors. Adiponectin induced a significant decline in the ATP levels, Ki-67 expression, cells in the G2/M phase, and nucleolar integrity in UM cultures. Conclusions: Adiponectin deficiency appears to enhance the metastatic potential of the UM cells with monosomy-3 and the termination of tumor dormancy. Counteracting insulin resistance and improving the serum adiponectin levels might therefore be a valuable approach to prevent or delay the UM metastases.


Assuntos
Adiponectina/metabolismo , Cromossomos Humanos Par 3 , Melanoma/metabolismo , Monossomia , Receptores de Adiponectina/metabolismo , Neoplasias Uveais/metabolismo , Trifosfato de Adenosina/metabolismo , Idoso , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Melanoma/genética , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia , Neoplasias Uveais/genética
18.
Obesity (Silver Spring) ; 28(6): 1075-1085, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32348021

RESUMO

OBJECTIVE: Identifying novel approaches to combat obesity is important to improve health span. It was hypothesized that methionine restriction (MR) will induce weight loss in obese mice by reducing adipose tissue mass caused by increased energy expenditure and reprogramming of adipose tissue homeostasis. The roles of adiponectin (ADIPOQ) and fibroblast growth factor 21 (FGF21) during weight loss in MR mice were also tested. METHODS: Diet-induced obese (DIO) male C57BL/6J (wild type), Adipoq-deficient (Adipoq knockout [KO]), Fgf21-KO, and Adipoq-Fgf21 double-KO mice were used. Following a switch to high-fat control (DIO-CF, 60% fat/0.86% methionine) or MR (DIO-MR, 60% fat/0.12% methionine) diet, physiological parameters were measured, and inguinal and perigonadal adipose tissues were examined. RESULTS: Obese mice subjected to MR showed loss of body weight and adiposity, increased energy expenditure, and improved glucose tolerance that were independent of the actions of ADIPOQ and FGF21. MR induced reduction of circulating lipids, glucose, insulin, leptin, and insulin like growth factor 1 and increased ß-hydroxybutyrate, ADIPOQ, and FGF21 concentrations. In fat, MR upregulated protein levels of adipose triglyceride lipase, apoptosis-inducing factor, lysosomal-associated membrane proteins 1 and 2, autophagy-related protein 5, beclin-1, and light chain 3B I and II. CONCLUSIONS: MR reduction of adipose tissue mass in obese mice is associated with elevated lipolysis, apoptosis, and autophagy and occurs independently of the actions of ADIPOQ and FGF21.


Assuntos
Adiponectina/metabolismo , Adiposidade/fisiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Metionina/metabolismo , Camundongos Obesos/genética , Perda de Peso/fisiologia , Animais , Masculino , Camundongos
19.
Ann Hum Biol ; 47(3): 244-249, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32279531

RESUMO

Background: Leptin and adiponectin interact with each other in the modulation of obesity and insulin resistance (IR) and it is also important to consider the role of cardiorespiratory and muscular fitness in these relationships.Aim: To analyse the relationship between IR with adipocytokines in children, and to test the mediation effect of %BF (percentage of body fat) in the association of IR with leptin, adiponectin, and L/A ratio.Subjects and methods: This cross-sectional study comprised a sample of 150 schoolchildren, aged 6-11 years, from school in Porto Alegre, Brazil. The following variables were evaluated: cardiorespiratory fitness (CRF), muscular fitness (MF), percentage of body fat (%BF), and biochemical variables (leptin, adiponectin, glucose, and insulin).Results: IR was associated with leptin and L/A ratio, after adjustments for age, sex, sexual maturation, and CRF. When adjusted for age, sex, sexual maturation, and MF, an association was found between IR with leptin and L/A ratio. Moreover, %BF was a mediator in the association between IR and leptin, as well as IR and L/A ratio, explaining 54% and 57% of these associations, respectively.Conclusion: Leptin and L/A ratio are positively associated with IR after adjustments. Also, %BF is a mediator in the associations between IR and leptin and L/A ratio.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Adiposidade , Resistência à Insulina , Leptina/metabolismo , Brasil , Criança , Estudos Transversais , Humanos
20.
Adv Clin Exp Med ; 29(4): 449-452, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32343888

RESUMO

BACKGROUND: Diabetic retinopathy is one of the most common eye diseases faced by diabetic patients. It is a slow-progressing complication that results from damage to the blood vessels of the retina. OBJECTIVES: To investigate the role of adiponectin and inflammatory cytokines in the vitreous of diabetic rats. MATERIAL AND METHODS: The study was conducted in 3-4-month-old male albino Wistar rats (180-240 g). The animals were divided into 2 groups (n = 40 in each group): the diabetes group and the control group. A single dose of streptozotocin (STZ) (45 mg/kg) in citrate buffer (0.1 M; pH 4.5) was intraperitoneally (ip.) injected into the diabetes group rats. A single dose of citrate buffer was injected ip. into the control group rats. All subjects were sacrificed under intramuscular (im.) Na-thiopental (50 mg/kg) anesthesia. The rats' eyelids were opened with an eye speculum and vitreous samples were collected with 20G needles 4 mm posterior to the limbus. The levels of vitreous adiponectin, tumor necrosis factor α (TNF-α), interferon γ (INF-γ), and matrix metalloproteinase (MMP)-2 and -9 were determined using a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of adiponectin, TNF-α, INF-γ, MMP-2, and MMP-9 in the rat vitreous were significantly higher in the diabetes group than in the control group (p < 0.05). CONCLUSIONS: Elevated adiponectin, TNF-α, and INF-γ levels in the vitreous may be diagnostically useful in diabetic retinopathy, and inflammatory cytokines in the vitreous may be pathogenically important in this concentration.


Assuntos
Adiponectina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Corpo Vítreo/metabolismo , Animais , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA