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1.
J Cell Mol Med ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33124187

RESUMO

Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic ß-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor. The aim of this study was to explore the role of NR4A1 in counteracting JNK activation induced by ER stress or ROS and the related mechanism. qPCR, Western blotting, dual-luciferase reporter and ChIP assays were applied to detect gene expression or regulation by NR4A1. Immunofluorescence was used to detect a specific protein expression in ß-cells. Our data showed that NR4A1 reduced the phosphorylated JNK (p-JNK) in MIN6 cells encountering ER stress or ROS and reduced MKK4 protein in a proteasome-dependent manner. We found that NR4A1 increased the expression of cbl-b (an E3 ligase); knocking down cbl-b expression increased MKK4 and p-JNK levels under ER stress or ROS conditions. We elucidated that NR4A1 enhanced the transactivation of cbl-b promoter by physical association. We further confirmed that cbl-b expression in ß-cells was reduced in NR4A1-knockout mice compared with WT mice. NR4A1 down-regulates JNK activation by ER stress or ROS in ß-cells via enhancing cbl-b expression.

2.
Life Sci ; 257: 118028, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32615185

RESUMO

AIMS: Sertoli cells (SCs) play an important role in the process of spermatogenesis. SCs provide energy for germ cells (GCs) and themselves through glycolysis and fatty acid oxidation (FAO) respectively. High fat diet (HFD) impairs spermatogenesis by damaging function of SCs, however whether HFD disrupts energy metabolism in SCs remains unclear. MAIN METHODS: To explore this hypothesis, we built male Wistar rat model fed on HFD and cultured rats' primary SCs with palmitic acid (PA). Rats' fertility and sperm quality were evaluated in vivo. Glycolysis, lactate production and mitochondrial respiration were assessed by using extracellular flux analyzer, and the expression of enzymes involved in glucose and FAO was analyzed by Real-Time PCR or Western Blotting. KEY FINDINGS: The showed that the sperm concentration and pups per litter significantly decreased in rats fed on HFD compared to those rats fed on normal diet. There was an elevation of lactate levels in testicular tissue of rats fed on HFD and primary SCs exposed to PA. In vitro, PA increased glycolytic flux, and lactate production, and the levels of carnitine palmitoyltransferase I (CPT1) and long chain acyl-CoA dehydrogenase (LCAD) which were two key enzymes for fatty acid ß oxidation. Further analysis showed that mitochondrial respiration was impaired by PA, followed by the decrease in ATP turnover, maximal respiration and the increase in proton leak. SIGNIFICANCE: Taken together, the elevated lactate level, lipid metabolism disorder and mitochondrial dysfunction caused by HFD lead to SCs dysfunction, which ultimately leads to decreased sperm quality.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Células de Sertoli/metabolismo , Espermatogênese/fisiologia , Animais , Metabolismo Energético , Ácidos Graxos/metabolismo , Glucose/metabolismo , Glicólise , Insulina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Masculino , Oxirredução , Ácido Palmítico , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
4.
Horm Metab Res ; 52(10): 712-717, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32365399

RESUMO

Although subacute thyroiditis (SAT) is thought to be a self-limited inflammatory thyroid disease, the recurrence rate of SAT is approximately 10-20%. It is difficult for these patients to stop glucocorticoid treatment, and they are usually bothered with recurrent pain and the side effects of glucocorticoids for more than several months. We describe three cases who were diagnosed with recurrent subacute thyroiditis after a reduction in prednisolone (PSL) dose, either immediately upon the cessation of PSL or shortly thereafter. Their symptoms, including the adverse effects of PSL, severely impacted their quality of life. After a complete assessment, we administered colchicine at 1 mg per day for 1-2 months to control the recurrence of SAT and monitored their routine blood parameters every two weeks. All 3 patients were successfully tapered off of PSL treatment and were free of frequently recurrent SAT. Colchicine may be therapeutic in patients with prednisolone-refractory, recurrent SAT. However, a large-scale, double-blind, controlled, prospective multicenter study is required to provide a solid body of evidence.

6.
Minerva Endocrinol ; 45(2): 106-116, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32340426

RESUMO

BACKGROUND: Cystatin C is a marker of renal function and risk factor for cardiovascular disease. Patients with acute myocardial infarction showed a significant decrease in cystatin C levels. It is unknown whether reduced serum cystatin C levels are connected to acute events or represent a negative acute phase response. The current study aimed to assess the association between cystatin C and the existence of diabetic ketoacidosis (DKA), an acute event in individuals with type 1 diabetes mellitus (T1DM). METHODS: Cystatin C was measured in the control group (N.=322) and in T1DM patients with (N.=161) and without DKA (N.=146). Data were compared according to diabetes and ketoacidosis status. Correlation analysis was used to identify factors associated with cystatin C levels. A multiple stepwise regression analysis was used to determine which of the parameters that were significantly correlated with cystatin C in univariate analysis were independently related to cystatin C. Then, we assessed the independent association between cystatin C and the occurrence of DKA in T1DM patients. RESULTS: Serum cystatin C levels were lower in patients with DKA than in patients without DKA. After adjustment for age, sex, fasting plasma glucose and creatinine, cystatin C was positively correlated with the duration of diabetes, systolic blood pressure (SBP), total cholesterol, triglycerides, uric acid and low-density lipoprotein cholesterol (P=0.004, P=0.022, P=0.013, P=0.035, P=0.006, P=0.012, respectively) and negatively correlated with hemoglobin (P<0.001). The duration of diabetes (P<0.001), total cholesterol (P=0.002), hemoglobin (P<0.001), SBP (P=0.011) and serum creatinine (P<0.001) were independently associated with cystatin C. Furthermore, we found that cystatin C was independently associated with the occurrence of DKA in T1DM patients (OR=0.004, 95% CI: 0.000-0.079, P<0.001). CONCLUSIONS: Cystatin C was decreased in T1DM patients with DKA and was found to be an independent predictor of the occurrence of DKA in T1DM patients. The reduction in cystatin C levels might be significantly connected with acute events.

7.
Metab Syndr Relat Disord ; 18(5): 251-259, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32125926

RESUMO

Context: The link between obesity and bone health is controversial. Most studies classify obesity based on body mass index. However, differences in metabolic status may affect bone health. Purpose: To explore the potential relationship of metabolic obesity with forearm bone mineral density (BMD) in a northern Chinese population. Methods: This is a retrospective study involving a total of 2122 subjects divided into four groups: a metabolically healthy normal-weight (MHNW) group, a metabolically healthy obesity (MHO) group, a metabolically unhealthy, but normal-weight (MUNW) group, and a metabolically unhealthy obesity (MUO) group. Analysis of covariance was performed to compare forearm BMD among the groups. The covariates included age, weight, and height, along with menopause status in women. Partial correlation analysis and multiple linear regression models were used to explore the associations of forearm BMD with clinical parameters. Results: Young middle-aged men with MHO had significantly higher forearm BMD than those in the MUO group. In addition, forearm BMD of young middle-aged women was higher in the MHNW group than in the MUNW group. Partial correlation analysis and multiple linear regression analysis suggested that homeostasis model assessment of insulin resistance (HOMA-IR) was negatively correlated with forearm BMD in young middle-aged male subjects with MUO, and waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) showed a significant negative relationship with forearm BMD in young middle-aged female MUNW subjects. Conclusions: Men in the MUO group and women in the MUNW group were more likely to have lower forearm BMD if they were of young middle age. Metabolic obesity could be a better method for defining obesity when exploring the relationship between obesity and bone health in Chinese individuals. WC, LDL-C, and insulin resistance might be negative predictors of bone health.

8.
Oxid Med Cell Longev ; 2019: 9151067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583050

RESUMO

Background/Aims: Obesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males. Methods: An obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor κB (NF-κB) was assessed by immunofluorescence. Results: High-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-κB activity in Sertoli cells (SCs). Conclusion: Metformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.


Assuntos
Barreira Hematotesticular/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Obesidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Camundongos
9.
J Cell Mol Med ; 23(10): 6859-6871, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31373170

RESUMO

OBJECTIVE: The high-fat diet (HFD)-induced obesity is responsible for the testosterone deficiency (TD). However, the mechanism remains unknown. Mitochondrial homeostasis is proved to be important for maintaining the function of steroidogenic acute regulatory protein (StAR), the first rate-limiting enzyme in testosterone synthesis. As the key regulator of mitochondrial membrane permeability, cyclophilin D (CypD) plays a crucial role in maintaining mitochondrial function. In this study, we sought to elucidate the role of CypD in the expression of StAR affected by HFD. METHODS: To analyse the influence of CypD on StAR in vivo and in vitro, mouse models of HFD, CypD overexpression and CypD knockout (Ppif-/- ) as well as Leydig cells treated with palmitic acid (PA) and CypD overexpression plasmids were examined with an array of metabolic, mitochondrial function and molecular assays. RESULTS: Compared with the normal diet mice, consistent with reduced testosterone in testes, the expressions of StAR in both mRNA and protein levels in HFD mice were down-regulated, while expressions of CypD were up-regulated. High-fat intake impaired mitochondrial function with the decrease in StAR in Leydig cells. Overexpression of CypD inhibited StAR expressions in vivo and in vitro. Compared with C57BL/6 mice with HFD, expressions of StAR were improved in Ppif-/- mice with HFD. CONCLUSIONS: Mitochondrial CypD involved in the inhibitory effect of HFD on StAR expression in testes.

10.
PLoS One ; 14(5): e0216151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048873

RESUMO

Type 2 diabetes [T2D] and thyroid dysfunction [TD] often co-occur, have overlapping pathologies, and their risk increases with age. Since 1995, universal salt iodization has been implemented in China to prevent disorders caused by iodine deficiency. However, after two decades of implementation of universal salt iodization, the prevalence of TD in elderly Chinese patients with T2D is not well described and may have been underestimated. We conducted a questionnaire-based survey across 24 endocrinology centers in China between December 2015 and July 2016. Demographic and clinical data from 1677 patients with T2D were obtained and analyzed to examine the prevalence of TD along with T2D in these patients. We assessed TD prevalence according to the four TD subtypes [subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism], TD history, gender, and age. The diagnosis rates were calculated for TD and also for the TD subtype. The number of patients reaching treatment goals for T2D [hemoglobin A1c <7%] and TD [normal free thyroxine and thyroid-stimulating hormone [TSH]] and the incidences of complications and comorbidities were recorded. Among the enrolled patients with T2D [N = 1677], TD was diagnosed in 23.79% [399/1677] out of which 61% (245/399) were previously diagnosed and 38.59% (154/399) were newly diagnosed cases. Subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism were reported in 4.89%, 9.3%, 1.13%, and 3.16% of the total population, respectively. Among patients previously diagnosed with TD, the incidence in women [166/795; 20.88%] was higher than in men [79/882; 8.96%]. The treatment goals for TD and T2D were attained in 39.6% [97/245] and 34.41% [577/1677] of the cases, respectively. Diabetic complications and comorbidities were reported in 99.7% of patients, with peripheral neuropathy being the most common [43.46%] followed by cataract [24.73%]. We had found that the incidences of dyslipidemia, elevated LDL levels, and osteoporosis were significantly higher in patients with TD than those without TD. TD is underdiagnosed in elderly Chinese patients with T2D.


Assuntos
Doenças da Glândula Tireoide/epidemiologia , Glândula Tireoide/fisiopatologia , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertireoidismo/complicações , Hipotireoidismo/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários
11.
J Diabetes Res ; 2019: 4328975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949514

RESUMO

Aim: It is known that different stages of type 2 diabetes represent distinct pathophysiological changes, but how the spectrum of risk factors varies at different stages is not yet clarified. Hence, the aim of this study was to compare the effect of different metabolic variables on the natural history of type 2 diabetes. Methods: A total of 5,213 nondiabetic (normal glucose tolerance (NGT) and prediabetes) Chinese older than 40 years participated this prospective cohort study, and 4,577 completed the 3-year follow-up. Glycemic status was determined by standard oral glucose tolerance test both at enrollment and follow-up visit. Predictors for conversion in glycemic status were studied in a corresponding subcohort using the multiple logistic regression analysis. Results: The incidence of prediabetes and diabetes of the cohort was 93.6 and 42.2 per 1,000 person-years, respectively. After a 3-year follow-up, 33.1% of prediabetes patients regressed to NGT. The predictive weight of body mass index (BMI), serum triglyceride, total cholesterol, and systolic blood pressure in different paths of conversions among diabetes, prediabetes, and NGT differed. Specifically, BMI was the strongest predictor for regression from prediabetes to NGT, while triglyceride was most prominent for onset of diabetes. One SD increase in serum triglyceride was associated with a 1.29- (95% CI 1.10-1.52; P = 0.002) or 1.12- (95% CI 1.01-1.27; P = 0.039) fold higher risk of diabetes for individuals with NGT or prediabetes, respectively. Conclusion: Risk factors for different stages of diabetes differed, suggesting personalized preventive strategies for individuals with different basal glycemic statuses.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Dislipidemias/complicações , Obesidade/complicações , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Glicemia/metabolismo , Índice de Massa Corporal , China/epidemiologia , Feminino , Seguimentos , Intolerância à Glucose/complicações , Teste de Tolerância a Glucose , Humanos , Hiperglicemia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Triglicerídeos/sangue
12.
Life Sci ; 228: 215-220, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002916

RESUMO

AIMS: Small-for-gestational-age (SGA) fetus is an important public health issue because of its high mortality and long-term effects on health. Maternal hyperuricemia is associated with diverse adverse pregnant outcomes and neonatal disturbance. We aimed to evaluate whether maternal hyper-uric acid (HUA) is associated with the risk of SGA fetus and to explore whether it can modify the association between maternal hyper-blood pressure (HBP) and SGA fetus. MATERIALS AND METHODS: We performed a population-based cross-section retrospective study, a total of 6715 pregnant females were recruited. Multiple logistic regression analysis was performed to identify risk factors significantly correlated with SGA fetus, and then studied the effect of maternal HUA on the association between maternal HBP and SGA fetus. KEY FINDINGS: We collected 537 SGA fetuses among 6715 pregnant females. Maternal HUA was an independent risk factor for SGA delivery (odds ratio (OR), 2.737; 95% confidence interval (CI), 2.110-3.551). A dose-response association between maternal uric acid and SGA delivery was found among normotensive and hypertensive group. Compared with those whose uric acid was lower than 270 µmo/L with normal-blood pressure (NBP), the risk for SGA delivery in those whose uric acid was higher than 370 µmo/L with stage 2 or 3 hypertension increased 12.695-fold. SIGNIFICANCE: Our results suggest that maternal HUA could increase the risk of neonatal SGA, and maternal HUA could be superimposed upon pre-existing maternal HBP and increase the risk for SGA fetus.


Assuntos
Hipertensão/complicações , Hiperuricemia/complicações , Recém-Nascido Pequeno para a Idade Gestacional , Complicações na Gravidez/etiologia , Nascimento Prematuro/etiologia , Adulto , Pressão Sanguínea , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco
13.
Mol Med Rep ; 19(6): 4603-4612, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957178

RESUMO

As the incidence of osteoporosis (OP) and hypercholesterolaemia in men has increased, male OP has drawn more attention from clinicians worldwide. The present study sought to investigate the effects of cholesterol on male bone. Between July 2015 and October 2015, 216 men (aged ≥18 years) were recruited for this cross­sectional study. To test our clinical hypothesis, we designed two male animal models: Exogenous hypercholesterolaemia induced by a high­cholesterol diet (HCD) and endogenous hypercholesterolaemia induced by apolipoprotein E (ApoE) knockout. Finally, the direct effects of cholesterol on osteoblasts were observed in cell experiments. In our clinical studies, men with hypercholesterolaemia displayed a lower bone mineral density (BMD) and increased beta collagen cross­linking (beta­CTX) and type I anterior collagen amino terminal peptide (PINP) levels compared to those of the control subjects. Serum cholesterol levels were a significant independent predictor of BMD, beta­CTX and PINP and were negatively correlated with BMD and positively correlated with beta­CTX and PINP levels. Our animal experimental results validated our clinical results, as they also indicated that hypercholesterolaemia damages bone microstructure and reduces bone strength. Cholesterol directly increased osteoblast functional gene expression in vitro. Hypercholesterolaemia increases the risk of high­turnover osteoporosis in men at least in part by excessively promoting the activity of the remodelling pathway. In addition, hypercholesterolaemia damages the bone microstructure, resulting in osteopenia or OP and reduced bone strength, leading to a higher risk of fracture in men. We emphasize the importance of preventing and treating hypercholesterolaemia as well as monitoring bone metabolic markers and BMD in men with hypercholesterolemia for the effective prevention of bone loss and subsequent fracture. In addition, our findings provide a theoretical basis for the development of treatments for high cholesterol­induced osteoporosis in men.


Assuntos
Remodelação Óssea , Hipercolesterolemia/sangue , Osteoporose/sangue , Adulto , Animais , Biomarcadores/sangue , Reabsorção Óssea/sangue , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Estudos Transversais , Modelos Animais de Doenças , Humanos , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Fragmentos de Peptídeos/sangue , Ratos , Ratos Sprague-Dawley
14.
Mol Genet Genomic Med ; 7(6): e671, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30968594

RESUMO

BACKGROUND: Steroid 21-hydroxylase deficiency (21OHD) is the most common enzymatic defect, but the genotype-phenotype associations have not been well established in Chinese patients. Here, a Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder. METHODS: Mutation analysis of CYP21A2 gene, 21-hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype-phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported. RESULTS: Among the total cohort (72 patients), 47 patients (65.3%) were diagnosed as salt-wasting (SW) phenotype, 11 (15.3%) were simple virilizing (SV) type, and 14 (19.4%) were nonclassic (NC) type. The value of FSH and LH for prediction of the SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q, and p.L459-P464del) were detected and induced a significantly reduced 21-hydroxylase activity. Generally, disease severity can be predicted with the genotypes. The most common genotypes in Chinese population were I2G/I2G (12.5%), I2G/Large lesion (12.1%), I173N/I2G (10.3%), and I173N/Large lesion (9.2%). The SW form of CAH is prominent in deletion or intronic splice mutations, namely I2G/I2G (18.6%), I2G/Large lesion (17.2%) and Large lesion/Large lesion (8.6%). CONCLUSION: Four novel mutations were identified and a high consistency of genotype-phenotype association was found in SW CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease.

15.
Medicine (Baltimore) ; 98(11): e14896, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882706

RESUMO

How nonalcoholic fatty liver disease (NAFLD) is linked to atherosclerosis is still disputed. This study aimed to explore the association between NAFLD and atherosclerosis among adults in Shandong province, China.A total of 6849 individuals were enrolled in the final analyses for a community-based study. The relationship between NAFLD and atherosclerosis was evaluated after adjusting for common confounding factors.Hypertension, diabetes, and higher serum low-density lipoprotein cholesterol (LDL-c) level were positively correlated with NAFLD. An odds ratio (OR) (95% confidence interval [CI]) of 1.325 (range 1.157-1.518) for hypertension, 2.153 (range 1.814-2.555) for diabetes, and 1.161 (range 1.071-1.259) for LDL-c was noticed. These factors also were positively correlated with atherosclerosis, with an OR (95% CI) of 1.501 (range 1.286-1.751) for hypertension, 1.716 (range 1.414-2.084) for diabetes, and 1.344 (range 1.231-1.466) for LDL-c. The prevalence of metabolic syndrome was higher in the atherosclerosis+NAFLD group (81.8%) when compared with the NAFLD-only (30.3%), atherosclerosis-only (32.2%), and control (20.3%) groups (P <.01).NAFLD and atherosclerosis have common metabolic characteristics, such as hypertension, diabetes, and higher serum LDL-c level. Patients with NAFLD in combination with atherosclerosis were found to have a more severe metabolic burden and greater chances of having hypertension, diabetes, dyslipidemia, and higher metabolic syndrome scores than those in the other groups.


Assuntos
Aterosclerose/metabolismo , Metabolismo/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto , Idoso , Aterosclerose/epidemiologia , Aterosclerose/etiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/classificação , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Razão de Chances , Prevalência , Fatores de Risco
16.
J Cell Mol Med ; 23(5): 3140-3150, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30884106

RESUMO

Emerging epidemiological studies indicate that hypercholesterolaemia is a risk factor for testosterone deficiency. However, the underlying mechanism is unclear. Testicular Leydig cells are the primary source of testosterone in males. To identify the effect and mechanism of cholesterol overload on Leydig cell function, rats were fed with a HC (HC) diet to induce hypercholesterolaemia. During the 16-week feeding period, serum testosterone levels were reduced in a time-dependent manner in rats fed the HC diet. Accordingly, these steroidogenic enzymes within the Leydig cells, including steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage cytochrome P450 (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD), were down-regulated. Notably, the HC-fed rats showed evident endoplasmic reticulum (ER) stress in the testis, including a dilated ER as an evident pathological change in the Leydig cell ultrastructure, up-regulated ER stress biomarker (binding immunoglobulin protein) levels and activation of the activating transcription factor 6 (ATF6)-related unfolded protein response pathway. Further analysis showed that when 4-phenyl butyric acid (4-PBA) was used to block ER stress in HC-fed rats for 8 weeks, the testosterone deficiency was significantly alleviated. Our findings suggested that high dietary cholesterol intake affected serum testosterone levels by down-regulating steroidogenic enzymes and that activated ER stress might serve as the underlying mechanism.

17.
Metab Syndr Relat Disord ; 17(4): 217-222, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30741593

RESUMO

Background: Given its high incidence, thyroid nodule (TN) warrants public attention. Thyroid volume (TV) has also been associated with multiple factors, such as iodine deficiency and supply and body mass index. It is well known that metabolic syndrome (MetS) comprises many metabolic disturbances, with insulin resistance being its major component. Materials and Methods: The aim of this study was to investigate the relationship between TN and TV and MetS and its components in an iodine-adequate area in Asia. All participants were asked to complete a questionnaire. After excluding 938 individuals based on the exclusion criteria, we reviewed data from 927 of 1865 participants. Adopting MetS diagnostic criteria, we found 437 subjects to be MetS positive [MetS(+)] and 490 subjects to be MetS negative [MetS(-)], respectively. Multivariate linear regression was used to assess the relationship between TNs and MetS. Moreover, univariate binary logistic regression analyses were used to calculate odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the associations between different variables and TNs. Results: A total of 232 females and 205 males were MetS(+), as diagnosed using the International Diabetes Federation criteria. However, there were 330 females and 160 males in the group of MetS(-) individuals. The prevalence of TNs was 38.29% in the MetS(+) group and 17.79% in the MetS(-) group. After adjusting for systolic blood pressure, diastolic blood pressure, and gender, only high-density lipoprotein, waist circumference (WC), and age were related to TNs (OR = 0.45, 95% CI 0.27-0.75, P = 0.0023; OR = 1.04, 95% CI 1.02-1.06, P = 0.0036). The TV of all participants was 13.98 (11.24, 17.01) mL; 13.26 (10.62, 16.17) mL for females and 14.96 (11.83, 18.01) mL for males. It was found that only WC was related to TV, after controlling for sex and age (P = 0.02). Conclusions: The morbidity among TN patients in the MetS(+) group was higher than that among the MetS(-) group. High-density lipoprotein cholesterol emerged as a protective factor, and WC was a risk factor for TN. Moreover, TV was related to MetS, and WC was an independent risk factor for TV.

18.
Life Sci ; 220: 69-75, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30685450

RESUMO

OBJECTIVE: To explore the correlation of the viscus fat area (VFA) with the Framingham 10-year general cardiovascular disease risk in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 202 patients with T2DM were divided into two groups based on VFA (a VFA ≥ 100 cm2 group and a VFA < 100 cm2 group), or four groups based on sex and age (a middle-aged male group, an elderly male group, a middle-aged female group, and an elderly female group). The correlation between the Framingham 10-year general cardiovascular disease risk and body fat indexes was analyzed. RESULTS: Patients in the VFA ≥ 100 cm2 group had higher body fat indexes and Framingham Risk Scores (FRSs) and lower levels of high density lipoprotein-cholesterol (HDL-C) when compared to the VFA < 100 cm2 group (P < 0.05). Female patients had higher body fat mass (BFM) and body fat percentage (BFP) levels and a lower VFA when compared to male patients. The VFA was significantly higher in the elderly than in the middle-aged patients. The waist hip fat ratio (WHFR) was significantly higher in elderly females than in elderly males (P < 0.05). Elderly females had the highest FRS of all patients. Multiple stepwise regression analysis revealed the VFA as a contributor to the Framingham 10-year general cardiovascular disease risk after statistical correction for other multiple factors affecting cardiovascular disease risk. CONCLUSION: The VFA is an independent factor that contributes to the Framingham 10-year general cardiovascular disease risk in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Tecido Adiposo , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , HDL-Colesterol/análise , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/metabolismo , Gordura Intra-Abdominal/citologia , Estudos Longitudinais , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Fatores de Risco
19.
Med Sci Monit ; 25: 590-597, 2019 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30698163

RESUMO

BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS. MATERIAL AND METHODS Databases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results. RESULTS Meta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, -0.43; 95% CI, -0.81-0.06; p=0.02; I²=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, -0.63; 95% CI, -1.20 - -0.05; p=0.03; I²=38%) but simvastatin did not significantly reduce DHEA levels (SMD: -0.14; 95% CI, -0.49-0.28; p=0.43; I²=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, -0.61; 95% CI, -1.23-0.02; p=0.06; I²=85%) and 24 weeks (SMD, -0.34; 95% CI -0.95-0.28; p=0.29; I²=83%). CONCLUSIONS Meta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.


Assuntos
Desidroepiandrosterona/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Atorvastatina/uso terapêutico , China , Desidroepiandrosterona/análise , Desidroepiandrosterona/fisiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/sangue , Sinvastatina/uso terapêutico
20.
Cell Res ; 29(2): 151-166, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30559440

RESUMO

Menopause is associated with dyslipidemia and an increased risk of cardio-cerebrovascular disease. The classic view assumes that the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen. In addition to a decrease in estrogen, circulating follicle-stimulating hormone (FSH) levels become elevated at menopause. In this study, we find that blocking FSH reduces serum cholesterol via inhibiting hepatic cholesterol biosynthesis. First, epidemiological results show that the serum FSH levels are positively correlated with the serum total cholesterol levels, even after adjustment by considering the effects of serum estrogen. In addition, the prevalence of hypercholesterolemia is significantly higher in peri-menopausal women than that in pre-menopausal women. Furthermore, we generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX) mice, in which a normal level of estrogen (E2) was maintained by exogenous supplementation. Consistently, the results indicate that FSH, independent of estrogen, increases the serum cholesterol level in this mouse model. Moreover, blocking FSH signaling by anti-FSHß antibody or ablating the FSH receptor (FSHR) gene could effectively prevent hypercholesterolemia induced by FSH injection or high-cholesterol diet feeding. Mechanistically, FSH, via binding to hepatic FSHRs, activates the Gi2α/ß-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter, thus preventing FoxO1 from repressing SREBP-2 gene transcription. This effect, in turn, results in the upregulation of SREBP-2, which drives HMGCR nascent transcription and de novo cholesterol biosynthesis, leading to the increase of cholesterol accumulation. This study uncovers that blocking FSH signaling might be a new strategy for treating hypercholesterolemia during menopause, particularly for women in peri-menopause characterized by FSH elevation only.


Assuntos
Colesterol/biossíntese , Hormônio Foliculoestimulante Humano/antagonistas & inibidores , Hormônio Foliculoestimulante Humano/sangue , Hipercolesterolemia/epidemiologia , Fígado/metabolismo , Menopausa/metabolismo , Adulto , Animais , Anticorpos/farmacologia , Anticolesterolemiantes/farmacologia , Estudos Transversais , Modelos Animais de Doenças , Estrogênios/metabolismo , Feminino , Células Hep G2 , Humanos , Hipercolesterolemia/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Prevalência , RNA Interferente Pequeno/genética , Receptores do FSH/genética , Receptores do FSH/metabolismo
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