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1.
Cell Physiol Biochem ; 52(6): 1398-1411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31075190

RESUMO

BACKGROUND/AIMS: Visfatin is known to act as a mediator in several metabolic disorders, such as obesity, diabetes, and cardiovascular diseases. This study aimed to investigate the effect of visfatin on the adhesion of THP-1 monocytes to human vascular endothelial cells and the underlying mechanism. METHODS: Monocytes adhesion to endothelial cells was determined by using fluorescence-labeled monocytes. ICAM-1 and VCAM-1 expression in endothelial cells were measured by western blotting. Production of reactive oxygen species (ROS) was measured by using a fluorescent dye. The amounts of nuclear factor-kappa B (NF-κB) and phosphorylation of inhibitory factor of NF-κB (IκB) were determined by using western blot analysis. The translocation of NF-κB from the cytoplasm to the nucleus was determined by using immunofluorescence. RESULTS: Here we showed that visfatin significantly caused the upregulation of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells, as well as enhanced monocyte adhesion to endothelial cells. Moreover, we found that inhibition of PI3K, Akt, and p38 MAPK activation significantly prevented visfatin-enhanced expression of ICAM-1 and VCAM-1 and monocyte adhesion to endothelial cells. Visfatin enhanced ROS production and IKK/NF-кB activation and then led to upregulation of ICAM-1 and VCAM-1 and enhanced monocyte adhesion to endothelial cells. These effects were also p38/PI3K/Akt-dependent. CONCLUSION: These results demonstrated that visfatin promoted monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression via the activation of p38/PI3K/Akt signaling and downstream ROS production and IKK/NF-кB activation.


Assuntos
Adesão Celular/efeitos dos fármacos , Nicotinamida Fosforribosiltransferase/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Monócitos/citologia , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
2.
J Endocrinol ; 231(2): 109-120, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27539963

RESUMO

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.


Assuntos
Modelos Animais de Doenças , Gordura Intra-Abdominal/patologia , Córtex Renal/patologia , Obesidade/fisiopatologia , Podócitos/patologia , Insuficiência Renal Crônica/patologia , Células 3T3-L1 , Adipócitos Brancos/metabolismo , Adipócitos Brancos/patologia , Adiposidade , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Linhagem Celular , Meios de Cultivo Condicionados , Dieta Hiperlipídica/efeitos adversos , Progressão da Doença , Regulação da Expressão Gênica , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Córtex Renal/metabolismo , Córtex Renal/fisiopatologia , Córtex Renal/ultraestrutura , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Obesidade/etiologia , Tamanho do Órgão , Podócitos/metabolismo , Podócitos/ultraestrutura , Ratos Sprague-Dawley , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia
3.
Obesity (Silver Spring) ; 24(3): 643-53, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26833777

RESUMO

OBJECTIVE: The aim of this study was to investigate the regulatory mechanism of endothelin-1 (ET-1), an endothelium-derived vasoconstrictor, on adipogenesis in vitro and in vivo. METHODS: 3T3-L1 preadipocytes were used to explore the mechanisms mediating ET-1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET-1, male Sprague-Dawley rats were infused with ET-1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured. RESULTS: ET-1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET-1, via ETAR, inhibited adipocyte differentiation partially through an ERK-dependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET-1- or saline-infused rats. Compared with saline-infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET-1-infused rats. CONCLUSIONS: Chronic ET-1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET-1-stimulated preadipocyte proliferation, but not ET-1-suppressed adipocyte differentiation.


Assuntos
Adipócitos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Endotelina-1/farmacologia , Hiperplasia/etiologia , Receptor de Endotelina A/efeitos dos fármacos , Células 3T3-L1/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotelina-1/metabolismo , Hiperplasia/metabolismo , Masculino , Camundongos , Obesidade/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor de Endotelina A/metabolismo
4.
Shock ; 45(4): 460-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26536203

RESUMO

BACKGROUND: Visfatin is produced in and secreted from adipocytes. Increased circulating visfatin level is observed in obese subjects. Previous studies demonstrated that visfatin was involved in obesity-related cardiovascular diseases. AIMS: This study aims to explore the regulatory effects of adipokine visfatin on foam cell formation, a key step in the development of atherosclerosis. METHODS: Effect of visfatin on protein and mRNA expression of scavenger receptor and ATP binding cassette transporter in RAW264.7 macrophages were measured by western blotting and real-time RT-PCR. To confirm the influence of visfatin-regulated scavenger receptor and ATP binding cassette transporter to foam cell formation, the visfatin-caused changes of ox-LDL uptake, cholesterol efflux, and foam cell formation were determined. RESULTS: Visfatin significantly increased the expression of CD36 and scavenger receptor A (SRA), decreased the expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), and had no effect on the expression of SR-B1. Visfatin increased oxidized-LDL (ox-LDL) uptake and decreased cholesterol efflux, which increased foam cell formation. The PI3K inhibitor LY294002 blocked the effect of visfatin on the protein and mRNA expression levels of CD36, SRA, and ABCG1 and ox-LDL uptake and cholesterol efflux. The ERK inhibitor PD98059 also prevented visfatin-induced ABCA1 instability and subsequently decreased cholesterol efflux. CONCLUSIONS: Visfatin upregulated CD36 and SRA expression and downregulated ABCA1 and ABCG1 expression, subsequently increased ox-LDL uptake and decreased cholesterol efflux, and finally promoted foam cell formation via the PI3K- and ERK-dependent pathways.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/biossíntese , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese , Antígenos CD36/biossíntese , Citocinas/metabolismo , Células Espumosas/metabolismo , Regulação da Expressão Gênica , Nicotinamida Fosforribosiltransferase/metabolismo , Receptores Depuradores/biossíntese , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Linhagem Celular , Células Espumosas/patologia , Sistema de Sinalização das MAP Quinases , Camundongos
5.
PLoS One ; 10(5): e0125935, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26011530

RESUMO

BACKGROUND: Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children. METHODS: We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits. RESULTS: Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%). CONCLUSIONS: Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.


Assuntos
Hiperlipidemias/sangue , Hiperlipidemias/complicações , Inflamação/sangue , Inflamação/complicações , Insulina/sangue , Obesidade/sangue , Obesidade/complicações , Adolescente , Biomarcadores/sangue , Criança , Humanos , Masculino , Análise de Componente Principal , Taiwan
6.
Eur J Pharmacol ; 709(1-3): 85-92, 2013 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-23528357

RESUMO

The mechanisms underlying insulin sensitivity and fat tissue distribution in chronic renal insufficiency remain unclear. Previous studies have shown the benefits of angiotensin II receptor blockers on moderately nourished to well-nourished patients with the metabolic syndrome. The current study explored the effect of losartan, the first selective angiotensin II receptor blocker, on insulin sensitivity and visceral fat tissue distribution in a 5/6 nephrectomized (N) rat model and investigated the expression of adipose tissue adipocytokines. Male Sprague-Dawley rats (200 g to 250 g) were subjected to 5/6 nephrectomy, and the adipocytes isolated from the visceral fat tissues were then studied. Results showed that desmin expression was significantly suppressed and systolic blood pressure was successfully normalized in the losartan-administered (NA) group. The weight of the visceral fat pad remarkably decreased in the N and NA groups (100 mg/500 ml drinking water) compared with the control group. The weight did not decrease further in the NA group compared with the N group. Insulin resistance was more remarkable in the N group compared with the control and NA groups. Moreover, the adipose tissue expression of adiponectin and leptin was downregulated whereas that of resistin was upregulated in the N group compared with the control group. However, the adiponectin, leptin, and resistin adipose tissue expression returned to their basal values in the NA group. These findings indicated that losartan administration ameliorated renal injury, systolic blood pressure, and adipocytokine imbalance of the adipose tissue in chronic renal insufficiency. Insulin sensitivity was not improved.


Assuntos
Adipocinas/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/prevenção & controle , Gordura Intra-Abdominal/efeitos dos fármacos , Losartan/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Adipocinas/antagonistas & inibidores , Adipocinas/genética , Adiposidade/efeitos dos fármacos , Animais , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão/etiologia , Resistência à Insulina , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Rim/fisiopatologia , Masculino , Nefrectomia/efeitos adversos , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/fisiopatologia
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