RESUMO
BACKGROUND: Recent studies have demonstrated a protective effect of osteocalcin (OCN) on glucose homeostasis and metabolic syndrome. However, its role in vascular function remains unknown. This study investigated the contribution of OCN to the pathogenesis of endothelial dysfunction in the thoracic aorta of apolipoprotein E-deficient (ApoE-KO) mice. METHODS: Eight-week-old ApoE-KO mice were given chow or high fat diet (HFD) for 12 weeks with or without daily intraperitoneal injection of OCN. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT),measurement of serum lipid profiles and blood pressure were carried out. Endothelium-dependent relaxation (EDR) was measured by wire myography. Human umbilical vein endothelial cells (HUVECs) were used to study the role of OCN on eNOS levels in vitro. PI3K inhibitor (LY294002) and Akt inhibitor V were used ex-vivo to determine whether PI3K/Akt/eNOS contributes to the beneficial effect of OCN for the vascular or not. RESULTS: Daily injections of OCN can significantly improve lipid metabolism, glucose tolerance and insulin sensitivity in ApoE-KO mice. In ApoE-KO mice fed with HFD, the OCN-treated mice displayed an improved acetylcholine-stimulated EDR compared to the vehicle-treated group. In addition, compared to vehicle-treated HUVECs, OCN-treated HUVECs displayed increased activation of the Akt-eNOS signaling pathway, as evidenced by significantly higher levels of phosphorylated Akt and eNOS. Furthermore, a similar beneficial effect of OCN on thoracic aorta was observed using ex vivo organ culture of isolated mouse aortic segment. However, this effect was attenuated upon co-incubation with PI3K inhibitor or Akt inhibitor V. CONCLUSIONS: Our study demonstrates that OCN has an endothelial-protective effect in atherosclerosis through mediating the PI3K/Akt/eNOS signaling pathway.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Endotélio Vascular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Osteocalcina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Vasodilatação/fisiologia , Animais , Apolipoproteínas E/deficiência , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Técnicas de Cultura de Órgãos , Osteocalcina/farmacologia , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Vasodilatação/efeitos dos fármacosRESUMO
AIM: Considering the characterization of vitamin D deficiency as a risk factor of ectopic fat deposition, the association of serum 25-hydroxy vitamin D3 [25(OH)D3] levels with non-alcoholic fatty liver disease (NAFLD) was evaluated in Chinese men with normal body mass index (BMI) and enzyme markers of liver function. METHODS: A total of 514 participants (22 to 79 years old) with normal BMI and liver enzymes were identified for analysis. Abdominal ultrasound was performed to diagnose NAFLD, and the fatty liver index (FLI) was calculated to quantify liver steatosis. Serum 25(OH)D3 levels were determined by an electrochemiluminescence immunoassay. RESULTS: Among the entire study population, the mean levels of serum 25(OH)D3 were 15.32±5.77 ng/mL. However, when serum 25(OH)D3 levels were compared between non-NAFLD subjects (n=438) and NAFLD subjects (n=76), the latter showed significantly lower levels (15.65±5.89 ng/mL vs 13.46±4.65 ng/mL, P=0.002). In addition, serum 25(OH)D3 levels were found to be significantly correlated with FLI after adjustment for age and BMI (r=-0.108, P=0.014). Logistic regression showed that serum 25(OH)D3 levels were independently correlated with NAFLD (OR: 0.937, 95% CI: 0.884-0.993, P=0.028). Furthermore, stepwise regression analysis revealed that serum 25(OH)D3 levels were inversely associated with FLI (ß=-0.055, P=0.040). CONCLUSION: The present study demonstrated that serum 25(OH)D3 levels were inversely associated with NAFLD, even in subjects with normal total body fat, suggesting a potential role of lower levels of vitamin D in the occurrence and development of NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica/sangue , Vitamina D/sangue , Adulto , Idoso , Povo Asiático , Humanos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Vitamina D/metabolismo , Adulto JovemRESUMO
1. Perturbed serum vitamin D levels have been shown to be associated with increased risk of cardiovascular disease. The aim of the present study was to investigate the association of serum 25-hydroxyvitamin D3 (25(OH)D3) levels and B ultrasonography-detected carotid plaque and carotid intima-media thickness (C-IMT) in Chinese middle-aged and elderly men. 2. In all, 1001 men, aged 45-78 years, were enrolled in the study. Increased C-IMT was defined as any C-IMT value in the highest quartile of the study subjects (≥ 0.75 mm). 3. The study population had a median serum 25(OH)D3 level of 14.51 ng/mL (interquartile range (IQR) 10.84-18.67 ng/mL). Subjects with carotid plaques had lower serum 25(OH)D3 levels than those without (13.80 (IQR 10.82-17.68) vs 14.74 (IQR 10.87-19.08) ng/mL, respectively; P = 0.029), and decreasing serum 25(OH)D3 levels were accompanied by increased C-IMT in both groups (13.24 (IQR 9.91-16.81) vs 14.45 (IQR 11.40-18.51) ng/mL, respectively (P < 0.05) in those with plaque; 13.80 (IQR 9.99-17.09) vs 14.99 (IQR 11.17-19.43) ng/mL, respectively (P < 0.01) in those without plaque). Multivariate logistic regression analysis showed that serum 25(OH)D3 levels were independently associated with carotid plaque (odds ratio (OR) 0.972; 95% confidence interval (CI) 0.946-0.998; P = 0.032). In addition, serum 25(OH)D3 levels were identified as an independent protective factor for increased C-IMT among subjects with plaque (OR 0.900; 95% CI 0.849-0.955; P = 0.001) and those without plaque (OR 0.944; 95% CI 0.908-0.981; P = 0.004). 4. Collectively, these findings suggest that serum 25(OH)D3 levels are inversely associated with atherosclerosis in Chinese middle-aged and elderly men.
Assuntos
Calcifediol/sangue , Idoso , Povo Asiático , Aterosclerose/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Artérias Carótidas/patologia , Espessura Intima-Media Carotídea , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The present study was designed to investigate the relationship between serum osteocalcin levels and non-alcoholic fatty liver disease (NAFLD) in Chinese men. In all, 1558 men (21-78 years old) were recruited to the study. Serum osteocalcin, glucose and lipid profiles were determined. Demographic and clinical characteristics were recorded. All participants underwent hepatic ultrasonographic examination. Serum osteocalcin levels were significantly lower in subjects with NAFLD than those without (P < 0.01). All study subjects were divided into four subgroups according to quartiles of serum osteocalcin levels. The frequency of NAFLD increased progressively with declining serum osteocalcin levels (P(trend) < 0.01). Serum osteocalcin levels were inversely correlated with NAFLD (P < 0.01). However, the significant association between serum osteocalcin levels and NAFLD disappeared in logistic regression analyses. Furthermore, multiple stepwise regression analysis showed that serum osteocalcin levels were independently associated with serum alanine aminotransferase levels in Chinese men (P < 0.01). The findings of the present study suggest that serum osteocalcin levels are not directly correlated with NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica/sangue , Osteocalcina/sangue , Adulto , Idoso , Povo Asiático , Glicemia/metabolismo , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto JovemRESUMO
BACKGROUND: Epidemiologic evidence of the effect of dietary selenium intake on stroke risk remains controversial. This study aimed to examine the cross-sectional correlation between dietary selenium intake and the risk of stroke in adults. MATERIALS AND METHODS: We retrospectively analysed 39,438 participants from the National Health and Nutrition Examination Survey 2003-2018, aged 20-85 years. Participants were divided into quartiles depending on daily dietary selenium intake: quartile 1 (0-77 µg), quartile 2 (77-108 µg), quartile 3 (108-148 µg), and quartile 4 (148-400 µg). The dose-response relationship was assessed using the restricted cubic spline function. RESULTS: The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of stroke were 0.70 (0.55, 0.88) for participants in quartile 2, 0.71 (0.53, 0.93) for quartile 3, and 0.61 (0.43, 0.85) for quartile 4 compared with that in quartile 1. p-Value for trend through quartiles was .007. A non-linear negative correlation between dietary selenium intake and stroke was observed in the threshold effect analysis and restricted cubic spline function (p-value for non-linearity < .001). An initial decrease in odds of stroke lower than 105 µg/day selenium intake (0.61 [0.44, 0.85], p = .004) was followed by a platform beyond 105 µg/day (0.97 [0.81, 1.16], p = .723). In the subgroup analysis, adjusted ORs (95% CIs) of stroke were 0.51 (0.36, 0.70) for female participants, 0.63 (0.40, 0.99) for participants with age <60 years, 0.63 (0.47, 0.85) for participants with poverty-income ratio < 2.14, 0.66 (0.50, 0.87) for participants with overweight and obesity, 0.66 (0.52, 0.84) for participants with hypertension, 0.72 (0.53, 0.97) for participants without diabetes, and 0.72 (0.56, 0.92) for non-anaemic participants. CONCLUSIONS: Dietary selenium had a negative and non-linear correlation with the risk of stroke in adults. The correlation varied across different population subgroups.KEY MESSAGESDietary selenium had a negative and non-linear correlation with the risk of stroke in adults.Non-linear negative correlation trends were observed in subpopulations of females, age <60 years, poverty-income ratio <2.14, overweight and obesity, hypertension, non-diabetes, and non-anaemia.Dietary selenium intake of approximately 105 µg per day has an optimum effect on stroke.
Assuntos
Diabetes Mellitus , Hipertensão , Selênio , Acidente Vascular Cerebral , Adulto , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Inquéritos Nutricionais , Obesidade , Sobrepeso , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
CONTEXT: Recent studies highlight a critical interaction between adipocyte fatty acid binding protein (A-FABP) and cardiovascular disorders. However, associations of A-FABP with subclinical atherosclerosis in a population with normal glucose tolerance remain unknown. OBJECTIVE: The study aimed to evaluate the relationship between A-FABP and carotid intima-media thickness (C-IMT) in a Chinese population with normal glucose tolerance. DESIGN AND SETTING: A cross-sectional analysis was conducted of 2253 cardiovascular disease-free normal glucose tolerance subjects (835 men, 1418 women; 20-78 years old) from the Shanghai Obesity Study. MAIN OUTCOME AND MEASURES: C-IMT was measured by B-mode ultrasound and used to assess subclinical atherosclerosis. Serum A-FABP levels were quantified by a sandwich ELISA. RESULTS: The median serum level for A-FABP was 4.0 ng/mL (interquartile range: 2.6-6.0 ng/mL), and significantly higher in women than men (P < .001). After adjusting for age and body mass index (BMI), a partial correlation analysis showed that A-FABP levels correlated with C-IMT in men, premenopausal, and postmenopausal women (P = .024, .006, and .016, respectively). Furthermore, C-IMT increased along with quartile A-FABP values (all P for trend <.001). Regression analyses demonstrated that A-FABP was associated with C-IMT only in women (P = .044 and .001 for pre- and postmenopausal, respectively). Moreover, A-FABP was identified as a risk factor for C-IMT in pre- and postmenopausal women with a normal BMI (P < .001 and P = .012, respectively). CONCLUSIONS: Serum A-FABP levels independently and positively correlate with subclinical atherosclerosis in pre- and postmenopausal Chinese women with normal glucose tolerance after adjustments for the traditional risk factors.
Assuntos
Aterosclerose/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Adulto , Idoso , Povo Asiático , Espessura Intima-Media Carotídea , China , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: Serum osteocalcin has been shown to be closely related to metabolic risk factors. Therefore, the aim of our study was to evaluate the association between serum osteocalcin levels and subclinical atherosclerosis in Chinese postmenopausal women. METHODS: A total of 1,319 postmenopausal women (age range, 41-78 y) without any history of cardiovascular disease or carotid plaque were analyzed. Electrochemiluminescence immunoassay was used to measure total serum osteocalcin levels. B-mode ultrasound measurement of carotid intima-media thickness (C-IMT) was used to evaluate subclinical atherosclerosis. Participants within the upper quartile of C-IMT measurements (≥0.65 mm) were classified as having increased C-IMT in the present study. C-IMT association with metabolic parameters was assessed by Spearman correlation analysis, whereas that with serum osteocalcin was assessed by multiple stepwise regression adjusted for potential confounders. RESULTS: The overall median (interquartile range) level of osteocalcin was 20.51 (16.71-24.98) ng/mL, and that of C-IMT was 0.60 (0.55-0.65) mm. Four hundred sixteen (31.5%) participants had increased C-IMT. Participants with increased C-IMT had significantly lower serum osteocalcin levels than those who had C-IMT lower than 0.65 mm (19.77 [16.17-24.52] vs 20.84 [16.92-25.39] ng/mL, P = 0.01). Serum osteocalcin level was significantly and negatively correlated with C-IMT (r = -0.107, P < 0.01) and was identified as an independent factor that significantly influenced C-IMT (standardized ß = -0.117, P < 0.01). CONCLUSIONS: Serum osteocalcin level is negatively associated with subclinical atherosclerosis in Chinese postmenopausal women.
Assuntos
Aterosclerose/sangue , Aterosclerose/diagnóstico por imagem , Espessura Intima-Media Carotídea/estatística & dados numéricos , Osteocalcina/sangue , Pós-Menopausa/sangue , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Imunoensaio/métodos , Medições Luminescentes/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Risco , Saúde da MulherRESUMO
OBJECTIVE: The relationship between serum osteocalcin levels and body fat distribution remains unclear. This study aimed to investigate the association between serum osteocalcin levels and visceral fat area (VFA) in Chinese men. DESIGN: Total serum osteocalcin levels were measured in 1768 Chinese men (22-75 yr old) by electrochemiluminescence immunoassay. VFA was quantified via magnetic resonance imaging. Correlation analyses were carried out for serum osteocalcin levels and clinical parameters. Subgroup analysis was carried out to confirm the correlations using subjects with normal glucose tolerance and normal body mass index chosen from the entire study population. RESULTS: Increased serum osteocalcin levels were accompanied by a decreasing trend in all anthropometric indices of obesity, systolic blood pressure, blood glucose, insulin resistance index, triglycerides, free fatty acid, and C-reactive protein levels (all P < 0.05). The 50-75th (osteocalcin level: 16.18-19.88 ng/ml) and 75th (≥19.89 ng/ml) percentile groups had lower VFA than the 25th (≤13.11 ng/ml) and 25-50th (13.12-16.17 ng/ml) percentile groups (96.0 ± 44.4 and 89.8 ± 44.4 cm(2) vs. 108.1 ± 41.9 and 102.9 ± 44.9 cm(2), P < 0.05). A decreasing trend in serum osteocalcin levels was found to accompany the increase in VFA. Multiple stepwise regression analysis showed that VFA, as an independent factor, was inversely associated with serum osteocalcin levels both in the entire study population and subgroup population (all P < 0.01). CONCLUSIONS: Serum osteocalcin levels were inversely correlated with VFA in Chinese men.
Assuntos
Povo Asiático , Gordura Intra-Abdominal/anatomia & histologia , Osteocalcina/sangue , Adulto , Idoso , Povo Asiático/estatística & dados numéricos , Distribuição da Gordura Corporal , Estudos de Casos e Controles , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/etnologia , Hiperlipidemias/patologia , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/patologia , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/etnologia , Obesidade Abdominal/patologia , Osteocalcina/análise , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Abnormal expression of 5'-methylthioadenosine phosphorylase (MTAP) is found in various tumor tissues. This study was to explore the correlation of MTAP expression to demethylation of MTAP promoter in colorectal cancer tissues. METHODS: The contents of MTAP mRNA in 50 colorectal cancer tissue samples and the adjacent normal tissues were detected by real-time PCR; expression of MTAP protein was detected by immunohistochemistry; methylation of MTAP promoter in colorectal cancer tissues and its adjacent normal tissues were detected by methylation-specified PCR (MSP). RESULTS: Compared with the adjacent normal tissues, the expression of MTAP mRNA was dramatically increased in colorectal cancer tissues (P<0.01). The positive rate of MTAP protein in colorectal cancer was significantly higher than that in colorectal adenoma and in adjacent normal tissues (98.0% vs. 85.0% and 12.5%, P<0.05), and the difference of the latter two groups was also significantly different (P<0.01). The methylation frequency of MTAP promoter was significantly lower in colorectal cancer group (32.0%) than in normal tissue (93.8%) and colorectal adenoma (75.0%) groups (P<0.01). CONCLUSIONS: Expression of MTAP is significantly higher in human colorectal cancer than in normal colorectal tissues. Demethylation of MTAP promoter may play an important role in up-regulating MTAP expression.