Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H: quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase / 中国天然药物

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.

Expression and Clinical Significance of NAMPT in Bone Marrow of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To study the expression level of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM), its relationship with clinical indicators, prognosis and potential role.@*METHODS@#Immunohistochemical staining was used to detect the expression of NAMPT in bone marrow biopsies of patients with newly diagnosed multiple myeloma (NDMM) and patients with iron deficiency anemia (IDA) hospitalized during the same period. According to the median expression level of NAMPT, NDMM patients were divided into high expression group and low expression group. The correlation between NAMPT expression level and clinical baseline data was analyzed, and survival analysis was performed to evaluate the relationship between NAMPT expression level and prognosis. The GSE24080 and GSE19784 datasets were used to analyze the effect of NAMPT on the prognosis. Gene set enrichment analysis (GSEA) explored the possible mechanism of NAMPT involved in MM cell function.@*RESULTS@#The mean staining intensity of NAMPT in bone marrow tissue of 31 NDMM patients was 0.007±0.002, and that of 10 IDA patients was 0.002±0.002 (P < 0.05). The median expression level of NAMPT was 0.0041 in NDMM patients, and the mean staining intensity of high expression group and low expression group was 0.007±0.005 and 0.002±0.001, respectively (P < 0.001). There were certain differences in lactate dehydrogenase (LDH), C-reactive protein (CRP) and ISS staging between high expression group and low expression group (P < 0.001), while no significant differences in other indicators. The overall response rate (ORR) of high expression group was significantly lower than that of low expression group (P < 0.001). The median survival time of patients in high expression group was significantly shorter than that in low expression group (P =0.024). The results of bioinformatics analysis showed that the event-free survival (EFS) rate and overall survival (OS) rate of low NAMPT group were both higher than high NAMPT group (P =0.037, P =0.009), and NAMPT was an independent prognostic factor for EFS and OS (P =0.006, P =0.020). GSEA suggested that NAMPT might affect MM cell function through mTORC1 signaling pathway.@*CONCLUSIONS@#The expression level of NAMPT in bone marrow of NDMM patients is significantly higher than that of IDA patients, and the high expression of NAMPT may be correlated with late ISS stage, and high level of LDH and CRP. Patients with high expression of NAMPT have worse response to bortezomib and survival time may be shorter. NAMPT may be involved in the occurrence and development of MM through mTORC1 signaling pathway.

Expression of NAMPT in Patients with Multiple Myeloma and Its Correlation with Clinical Manifestation / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression level of nicotinamide phosphoribosyltransferase (NAMPT ) in bone marrow of multiple myeloma (MM) patients and its correlation with clinicopathological features, clinical efficacy and prognosis.@*METHODS@#RT-qPCR and Western blot were used to detect the expression of NAMPT mRNA and protein in bone marrow mononuclear cells from 85 newly diagnosed MM patients (including 17 relapsed MM patients) and 15 healthy donors, and explore the correlation of the expression of NAMPT gene with clinicopathological features and efficacy. Kaplan-Meier method was used to analyze the effects of NAMPT on progression-free survival (PFS) and overall survival (OS), and univariate and multivariate survival analysis were performed.@*RESULTS@#The median expression level of NAMPT mRNA in bone marrow of newly diagnosed and relapsed MM patients was significantly higher than that of healthy donors (P <0.001). The expression of NAMPT mRNA in relapsed MM patients was significantly higher than that in newly diagnosed MM patients (P <0.001), which was consistent with the expression of NAMPT protein. ISS staging, lactate dehydrogenase and C-reactive protein levels, p53 deletion and the proportion of myeloma cells were increased in high NAMPT expression group compared with low NAMPT expression group (P <0.001). Compared with complete remission group, NAMPT mRNA expression was significantly up-regulated in partial remission group, progression group and relapsed group (P <0.001). The median OS and PFS of patients in high NAMPT expression group was 27.3 and 14.9 months, respectively, which was significantly shorter than 39.1 and 27 months in low NAMPT expression group (P =0.048, P <0.001). Both univariate and multivariate analysis showed that NAMPT expression was correlated with PFS and OS.@*CONCLUSION@#The expression level of NAMPT in newly diagnosed and relapsed MM patients is significantly higher than that in normal controls, and its up-regulation is related to the adverse clinical characteristics, efficacy and prognosis of MM patients. NAMPT is an independent prognostic risk factor of MM.

Measuring visfatin levels in saliva: an alternative approach to gestational diabetes screening

ABSTRACT Objective: Oral glucose tolerance testing (OGTT) is the current recommended approach for the diagnosis of gestational diabetes mellitus (GDM). Visfatin is a type of novel adipokine of interest that mostly participates in glucose metabolism and inflammatory processes. We aim to identify a screening technique for GDM using salivary visfatin levels and to establish this technique's value as a screening method compared to OGTT. Materials and methods: This is a cross-sectional case-control study. The cohort was formed from the saliva samples of pregnant patients in their 24th through 28th weeks of gestation. Patients were divided into two groups depending on their GDM status. OGTT and visfatin test results were compared and subjected to further analysis to establish a cutoff value for visfatin testing. Results: ELISA results indicated a significant difference between patients with GDM compared to patients without GDM; the values were 18.89 ± 9.59 and 12.44 ± 8.75, respectively (p: 0.007). A cutoff value of 10.5 ng/mL can be used to detect GDM with 78% sensitivity and 51% specificity. Conclusion: Salivary visfatin levels were significantly higher in patients with GDM. The existence of a differential in the concentration of visfatin in saliva can be utilized to develop a new screening method for GDM.

Investigation of serum vaspin, visfatin, chemerin and IL-18 levels in migraine patients / Investigação dos níveis séricos de vaspina, visfatina, quemerina e IL-18 em pacientes com migrânea

Abstract Background: Migraines are headaches caused by changes in the trigeminovascular metabolic pathway. Migraine headache attacks are associated with neurovascular inflammation, but their pathophysiological mechanisms have not been fully explained. Objective: To investigate the relationship between serum vaspin, visfatin, chemerin and interleukin-18 (IL-18) levels and the frequency of attacks in migraine headache. Methods: Three groups were established: migraine with aura (n = 50), migraine without aura (n = 50) and control group (n = 50). The migraine diagnosis was made in accordance with the International Classification of Headache Disorders-III beta diagnostic criteria. The analyses on serum vaspin, visfatin, chemerin and IL-18 levels were performed using the enzyme-linked immunosorbent assay method. Results: The serum vaspin, visfatin, chemerin and IL-18 levels were found to be significantly higher in the migraine patients than in the control group (p < 0.01). No statistically significant differences in serum vaspin, visfatin, chemerin and IL-18 levels were found among the migraine patients during attacks or in the interictal period (p>0.05). The serum visfatin and chemerin levels of the migraine patients were positively correlated with their serum IL-18 levels (p < 0.01), while their serum chemerin and visfatin levels were positively correlated with their serum vaspin levels (p < 0.05). Conclusions: This study showed that these biomarkers may be related to migraine pathogenesis. Nonetheless, we believe that more comprehensive studies are needed in order to further understand the role of vaspin, visfatin, chemerin and IL-18 levels in the pathophysiology of migraine headaches.

Resumo Introdução: A migrânea é causada por alterações nas vias metabólicas do sistema trigeminovascular. Crises de migrânea estão associadas à inflamação neurovascular, mas seus mecanismos patofisiológicos ainda não são totalmente explicados. Objetivo: Investigar a relação entre níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) e a frequência de crises de migrânea. Métodos: Três grupos foram formados: migrânea com aura (n = 50), migrânea sem aura (n = 50) e grupo controle (n = 50). A migrânea foi diagnosticada de acordo com os critérios da Classificação Internacional das Cefaleias (ICHD-III). As análises dos níveis séricos de vaspina, visfatina, quemerina e IL-18 foram realizadas utilizando-se o método imunoenzimático (ELISA). Resultados: Os níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) foram significativamente mais elevados em pacientes com migrânea do que no grupo controle (p < 0.01). Nenhuma diferença estatisticamente significativa foi observada nos níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) entre os pacientes com migrânea durante crises ou no período interictal (p>0,05). Os níveis séricos de visfatina e quemerina em pacientes com migrânea se correlacionaram positivamente com os níveis séricos de IL-18 (p < 0,01), ao passo que os níveis séricos de quemerina e visfatina se correlacionaram positivamente com os níveis séricos de vaspina (p < 0,05). Conclusões: Este estudo demonstrou que estes biomarcadores podem estar relacionados à patogênese da migrânea. Contudo, acreditamos que estudos mais abrangentes são necessários a fim de melhor compreendermos o papel dos níveis de vaspina, visfatina, quemerina e IL-18 na fisiopatologia da migrânea.

Effects of exercise type and intensity on visfatin and the metabolic syndrome in obesity / Efectos del tipo de ejercicio y de la intensidad en la visfatina y el síndrome metabólico en la obesidad / Efeitos do tipo de exercício e da intensidade na visfatina e a síndrome metabólica na obesidade

ABSTRACT Objective: Visfatin may regulate a variety of physiological functions and it has great potential to significantly enhance our knowledge of the treatment of metabolic syndrome. Metabolic syndrome (MS) refers to metabolic abnormalities, such as abdominal obesity, dyslipidemia, high low-density cholesterol, high blood pressure and diabetes, and physical activity is an important factor for the management of MS. Therefore, the purpose of this study is to investigate the effects of visfatin on MS and MS risk factors through differences in aerobic exercise intensity and exercise type based on the premise of the same amount of exercise (energy expenditure of 400 kcal per day). Method: Thirty two obese, middle-aged women were randomly assigned to exercise intensity groups VO2max 50% (MAE, n=8) and VO2max 80% (VAE, n=8) and to type of exercise groups VO2max 50% + TRX (MARE, n=8) and VO2max 80% + TRX (VARE, n=8). The exercise program was performed 5 times a week. The data was analyzed using two-way repeated measures ANOVA and post-hoc tests within groups with LSD. Results: Body weight (p<.01 and p<.001) and % body fat (p<.05 and p<.01) significantly decreased in all groups and visfatin only increased significantly after exercise in the VARE group (p<.05). TG, glucose, and waist circumstance (p<.05, p<.01, and p<.001) significantly decreased in all groups and HDL-C (p<.05) only increased significantly after exercise only in the MARE group. Conclusion: These results suggest that, in spite of differences in exercise intensity and exercise type, exercise is effective in improving obesity and MS risk factors, but further research is needed on the exact mechanisms of visfatin. Level of evidence I; Therapeutic Studies Investigating the Results of Treatment .

RESUMEN Objetivo: La visfatina puede regular diversas funciones fisiológicas y tiene gran potencial para mejorar significativamente nuestro conocimiento sobre el tratamiento del síndrome metabólico. El síndrome metabólico (SM) se refiere a anormalidades metabólicas, como obesidad abdominal, dislipidemia, colesterol de baja densidad elevado, hipertensión y diabetes, siendo la actividad física un factor importante para el manejo del SM. Siendo así, el objetivo de este estudio es investigar los efectos de la visfatina sobre los factores de riesgo de SM por medio de diferencias de la intensidad de ejercicios aeróbicos y del tipo de ejercicio, con base en la premisa de misma cantidad de ejercicio (gasto energético de 400 kcal por día). Método: Treinta y dos mujeres obesas de media edad fueron aleatoriamente designadas para grupos de intensidad de ejercicio con VO2máx de 50% (EAM, n = 8) y VO2máx de 80% (EAV, n = 8) y grupos con VO2máx de 50% + ERC (EARM, n = 8) y VO2máx de 80% + ERC (EARV, n = 8). El programa de ejercicios fue realizado cinco veces por semana. Los datos fueron analizados con ANOVA de dos vías con medidas repetidas y tests post-hoc en los grupos con DMS. Resultados: El peso corporal (p < 0,01 y p < 0,001) y porcentual de grasa corporal (p < 0,05 y p < 0,01) disminuyeron significativamente en todos los grupos y la visfatina sólo aumentó significativamente después del ejercicio en el grupo EARV (p < 0,05). Los triglicéridos, la glucosa y la circunferencia de la cintura (p < 0,05, p < 0,01 e p < 0,001) disminuyeron significativamente en todos los grupos y el HDL-C (p < 0,05) sólo aumentó significativamente después del ejercicio sólo en el grupo EARM. Conclusión: Esos resultados sugieren que, a pesar de las diferencias de intensidad y tipo de los ejercicios, los mismos son eficaces para mejorar la obesidad y los factores de riesgo del SM, por ende, son necesarias más investigaciones sobre los mecanismos exactos de la visfatina. Nivel de Evidencia I; Estudios terapéuticos - Investigación de los resultados del tratamiento .

RESUMO Objetivo: A visfatina pode regular diversas funções fisiológicas e tem grande potencial para aprimorar significativamente nosso conhecimento sobre o tratamento da síndrome metabólica. A síndrome metabólica (SM) refere-se a anormalidades metabólicas, como obesidade abdominal, dislipidemia, colesterol de baixa densidade elevado, hipertensão e diabetes, sendo a atividade física um fator importante para o manejo da SM. Assim sendo, o objetivo deste estudo é investigar os efeitos da visfatina sobre os fatores de risco de SM por meio de diferenças da intensidade de exercícios aeróbicos e do tipo de exercício, com base na premissa de mesma quantidade de exercício (gasto energético de 400 kcal por dia). Método: Trinta e duas mulheres obesas de meia-idade foram randomicamente designadas para grupos de intensidade de exercício com VO2máxde 50% (EAM, n = 8) e VO2máxde 80% (EAV, n = 8) e grupos com VO2máxde 50% + ERC (EARM, n = 8) e VO2máxde 80% + ERC (EARV, n = 8). O programa de exercícios foi realizado 5 vezes por semana. Os dados foram analisados com ANOVA de duas vias com medidas repetidas e testes post-hoc nos grupos com DMS. Resultados: O peso corporal (p < 0,01 e p < 0,001) e percentual de gordura corporal (p < 0,05 e p < 0,01) diminuíram significativamente em todos os grupos e a visfatina só aumentou significativamente depois do exercício no grupo EARV (p < 0,05). Triglicérides, glicose e circunferência da cintura (p < 0,05, p < 0,01 e p < 0,001) diminuíram significativamente em todos os grupos e o HDL-C (p < 0,05) só aumentou significativamente depois o exercício apenas no grupo EARM. Conclusão: Esses resultados sugerem que, apesar das diferenças de intensidade e tipo dos exercícios, eles são eficazes para melhorar a obesidade e os fatores de risco da SM, porém, são necessárias mais pesquisas sobre os mecanismos exatos da visfatina. Nível de Evidência I; Estudos terapêuticos - Investigação dos resultados do tratamento .

Study on visfatin-induced inflammation and necroptosis via LOX-1 in human umbilical vein endothelial cells / 生物医学工程学杂志

The aim of the study is to identify the effects and underlying mechanisms of visfatin on inflammation and necroptosis in vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with visfatin or pretreated with Polyinosinic acid (LOX-1 inhibitor). By using the Western blot, RT-PCR, immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), MTT and flow cytometry technique, the occurrence of inflammation and necroptosis in HUVECs were evaluated. Our results showed that 100 ng/mL visfatin significantly increased the mRNA and protein expression of monocyte chemotactic protein 1 (MCP-1) and LOX-1 after 24 hours' treatment in HUVECs. However, pretreatment with Polyinosinic acid could significantly reduce the expression of MCP-1 compared with visfatin group. Additionally, 100 ng/mL visfatin could induce the production of necrotic features and increase the mRNA expression of BMF (one of the markers of necroptosis), while pretreating with Polyinosinic acid markedly downregulated the mRNA expression of BMF gene and promoted the cell proliferation. These results indicate that visfatin might induce inflammation and necroptosis via LOX-1 in HUVECs, suggesting that visfatin plays a central role in the development of atherosclerosis.

Gingival crevicular fluid levels of visfatin in patients with chronic periodontitis and polycystic ovary syndrome

The role of visfatin levels in gingival crevicular fluid as a potential biomarker in the relationship between obesity and periodontal disease

Abstract Objectives Visfatin is an adipokine that plays an important role in immune functions as a growth factor, enzyme, and pro-inflammatory mediator. We aimed to determine the levels of visfatin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) in both obese/non-obese patients, with/without generalized chronic periodontitis (GCP). Methodology Patients were categorized as obese (O) (n=31) or non-obese (nO) (n=19). Groups were divided into four subgroups according to periodontal conditions: (1) periodontally healthy without obesity (nO-Ctrl); (2) GCP without obesity (nO-CP); (3) periodontally healthy with obesity (O-Ctrl); and (4) GCP with obesity (O-CP). Demographic variables, anthropometric and laboratory data were recorded. Periodontal parameters were measured at baseline and 3rd months after either non-surgical periodontal treatment or calorie -restricted diet therapy. At the same time, GCF samples were taken from patients to analyze TNF-alpha, IL-6,and visfatin levels. Results Periodontal parameters were significantly higher in the O group than in the nO group (P<0.05). IL-6 levels were higher in the O group than in the nO group (P<0.001). The visfatin levels of the obese patients were reduceddecreased following the treatments (P<0.05). Cholesterol levels were higher in the O group than in the nO groups (P<0.05). IL-6 levels were higher in O-CP and O-Ctrl groups than in the nO-Ctrl group (P<0.05). Compared to the other groups, visfatin levels were significantly higher in the O-CP group but decreased following treatment (P<0.05). Conclusions Our findings suggest that visfatin and IL-6 levels in GCF are associated with the pathogenesis of obesity and periodontitis. Within the limits of this study, we considered that there might be an association between the lipid profile and periodontitis on systemically healthy individuals.

Resistin and visfatin concentrations are related to central obesity and inflammation in Brazilian children

Background:The evidence that cardiovascular disease begins in childhood and adolescence, especially in the presence of excess weight, is associated with dysfunction on adipokine pro-inflammatory secretion. These affect glucose metabolism and lead to other complications related to insulin resistance and cardiovascular disease. This study assessed the association of anthropometric and metabolic parameters related to obesity, cardiovascular risk,and insulin resistance with concentrations of resistin and visfatin, in children. Methods: A cross-sectional study was developed with 178 children of 6­10 years old enrolled in public city schools. Anthropometric data, composition body, clinical, and biochemical were measured according to standard procedures. We used multiple regression models by stepwise method to evaluate the associations of resistin and visfatin with variables of interest.RESULTS: In healthy weight children, resistin was associated with LDL cholesterol, visfatin, atherogenic index, andwaist-to-height ratio, whereas in obese children resistin was associated with visfatin and interaction between conicity index and HOMA-AD. Furthermore, in healthy weight children, visfatin was associated to resistin and triceps skinfold thickness and negatively associated to HOMA-AD, while in obese ones visfatin was associated with waist-to-height ratio, atherogenic index, resistin, and interaction between trunk adiposity index and adiponectin and wasnegatively associated with the HOMA-IR index.CONCLUSIONS:Our study shows an association between anthropometric and biochemical variables related tovisceral fat and inflammation. These results suggest the resistin and visfatin as good pro-inflammatory markers. In addition, both adipokines are strongly related to central obesity, in children. In addition, both adipokines are strongly related to central obesity, in children.

Effects of Sodium Intake on the Association between the Salt-Sensitive Gene, Alpha-Adducin 1 (ADD1), and Inflammatory Cytokines in the Prevalence of Children Obesity

OBJECTIVE: To examine the effects of sodium intake on the correlations between the salt-sensitive gene α-adducin 1 (ADD1) and inflammatory cytokines in Korean childhood obesity. METHODS: A total of 2,070 students aged 8–9 years old participated in this study. The anthropometrics, serum biochemistry profile, inflammatory cytokines, and three-day dietary assessment were analyzed according to sex, obesity degree, and ADD1 polymorphism. RESULTS: The obesity prevalence was higher in boys (15.6%) than in girls (11.9%). Boys also showed higher values in anthropometrics; lipid, glucose, and insulin profiles; total calorie intakes, as well as those of sodium and calcium compared with those of the girls. The more obese were boys and girls, the higher were the anthropometrics and the blood levels (total cholesterol, triglyceride, low-density lipoprotein cholesterol, fasting blood sugar, and insulin), but the lower was high-density lipoprotein cholesterol. The obese boys had significantly higher sodium and Na/K intakes, while the obese girls had higher visfatin level and Na/K intake. In addition, an increase in the risk factors for blood pressure and obesity in ADD1 variants was identified. Serum tumor necrosis factor-α(TNF-α) significantly increased with increasing sodium intake in the ADD1 W allele carriers, regardless of sex. The presence of obesity with the ADD1 W allele induced inflammatory accelerators such as TNF-α or C-reactive protein(CRP) with higher sodium intake. CONCLUSION: Obese children with an ADD1w allele can experience a more complex form of obesity than non-obese when exposed to an obesity-inducing environment and need to be controlled sodium intake in the diet.

Effects of FK866 on migration of A549 cells and related mechanism / 浙江大学学报·医学版

OBJECTIVE@#: To investigate the effect of nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 on the migration of human non-small cell cancer A549 cells and related mechanism.@*METHODS@#: The inhibition effect of FK866 on A549 cells was tested by MTT assay. A549 cells were treated with 1.0 and 10.0 nmol/L FK866, and the cell migration was evaluated by modified wound scratch assay. The mRNA expression of E-cadherin and vimentin was detected by real-time RT-PCR, and the expression of ERK1/2 and pERK1/2 was determined by Western blotting.@*RESULTS@#: FK866 inhibited the proliferation of A549 cells in a time-and concentration-dependent manner; after treatment for 72 h, the IC of FK866 was 9.55 nmol/L. When 1.0 nmol/L or 10.0 nmol/L FK866 was continuously applied 48 h before and 48 h after a scratch was made in wound scratch assay, the migration of A549 cells was significantly inhibited. However, when the FK866 was applied only 48 h after the scratch, the migration of A549 cells was inhibited by 10.0 nmol/L but not by 1.0 nmol/L FK866. The mRNA expression of E-cadherin and vimentin, and the activated ERK1/2 were significantly increased after 1.0 nmol/L FK866 treatment for 72 h. The pretreatment with nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide(1.0 mmol/L) or ERK1/2 inhibitor U0126 (10.0 μmol/L) reversed the up-regulation of E-cadherin and vimentin expression induced by FK866.@*CONCLUSIONS@#s: Low concentration of FK866 decreases the migration of A549 cells through the inhibition of NAD level, activation of ERK1/2 and up-regulation of E-cadherin expression. However, it also up-regulates the expression of vimentin, indicating that it may have dual effects on the migration of tumor cells.

Long-term study of the association of adipokines and glucose variability with diabetic complications

BACKGROUND/AIMS: Recent studies have suggested an important role of adipokines in the development of insulin resistance and diabetes mellitus. The clinical relevance of adipokines on long-term outcomes in patients with diabetes and chronic kidney disease is uncertain. The purpose of this study was to identify a predictable factor in patients with long-term diabetic complications. METHODS: A total of 161 diabetic individuals were followed-up from 2002 to 2013. Circulating plasma levels of adiponectin, glypican-4, irisin, visfatin, and visit-to-visit glucose variability were measured in diabetic patients. Associations among adipokines and variable metabolic parameters and microvascular, and macrovascular complications were evaluated. RESULTS: Plasma adiponectin and glypican-4 levels were significantly increased in patients with renal insufficiency. These adipokines were negatively associated with estimated glomerular filtration rate and positively associated with urinary albumin excretion. The relative risk of renal progression to dialysis increased independently with increasing level of adiponectin. Glypican-4 and visfatin were not predictive of any microvascular or macrovascular complications. Glucose variability increased the risk of diabetic nephropathy and cerebrovascular complications. CONCLUSIONS: Adiponectin and glypican-4 were associated with renal function and might be able to predict renal progression. Glucose variability was a predictable factor for diabetic nephropathy and cerebrovascular complications.

Association of Adipokines with Development and Progression of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting 30% of the general population and 40% to 70% of obese individuals. Adipose tissue plays a crucial role in its pathogenesis, as it produces and secretes pro- and anti-inflammatory cytokines called adipokines. Adiponectin and leptin have well-determined actions in terms of NAFLD pathophysiology. Adiponectin deficiency is associated with a pro-inflammatory condition, as it is observed in obesity and other metabolic disorders. On the other hand, increased leptin levels, above the normal levels, act as a pro-inflammatory stimulus. Regarding other adipokines (resistin, visfatin, chemerin, retinol-binding protein 4, irisin), data about their contribution to NAFLD pathogenesis and progression are inconclusive. In addition, pharmacological agents like thiazolidinediones (pioglitazone and rosiglitazone), that are used in the management of NAFLD exert favourable effects on adipokine levels, which in turn may contribute to the improvement of liver function. This review summarizes the current knowledge and developments in the association between adipokines and NAFLD and discusses possible therapeutic implications targeting the modulation of adipokine levels as a potential tool for the treatment of NAFLD.

Serum visfatin levels in non-obese women with polycystic ovary syndrome and matched controls

OBJECTIVE: The purpose of the current study was to compare the circulating levels of visfatin between women with polycystic ovary syndrome (PCOS) and those without PCOS and to assess the correlations between visfatin levels and various parameters. METHODS: This case-control study recruited 74 PCOS patients and 74 age- and body mass index (BMI)-matched controls. Serum visfatin levels were evaluated using the enzyme-linked immunosorbent assay. Women with PCOS were divided into 2 subgroups based on the presence of clinical or biochemical hyperandrogenism. The possible differences in serum visfatin levels between the hyperandrogenic and non-hyperandrogenic groups were also assessed. RESULTS: Visfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients had significantly higher mean serum visfatin levels than those in non-hyperandrogenic patients (3.87 ng/mL; 95% confidence intervals [CIs], 3.09–4.85 in hyperandrogenic group vs. 2.69 ng/mL; 95% CIs, 2.06–3.52 in non-hyperandrogenic group; P=0.038). In women with PCOS, visfatin levels positively correlated with BMI (r=0.23; P=0.047) and the log free androgen index (FAI) (r=0.27; P=0.021) and negatively correlated with high-density lipoprotein (HDL) cholesterol levels (r=−0.37; P=0.025). Except for HDL cholesterol levels, these correlations were also observed in controls. CONCLUSION: Visfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients showed significantly higher serum visfatin levels than those of non-hyperandrogenic patients, and visfatin had a positive linear correlation with FAI in both PCOS patients and controls.

Body composition, resting energy expenditure and inflammatory markers: impact in users of depot medroxyprogesterone acetate after 12 months follow-up

ABSTRACT Objective The aim of this study was to evaluate for 12 months the changes of body weight using Depot Medroxyprogesterone Acetate (DMPA) and if these changes are related to inflammatory markers. Subjects and methods Twenty women of childbearing age who chose the DMPA, without previous use of this method, BMI < 30 kg/m2, and 17 women using IUD TCu 380A, participated in the study. At the baseline and after one year, changes in weight gain, body composition by the bioimpedance electric method, resting energy expenditure (REE) by the indirect calorimetry method, inflammatory markers and HOMA-IR were assessed. Results After 12 months of evaluation, we could observe a significant increase in the DMPA group in weight (3,01 kg) and BMI, while the IUD group’s only significant increase was observed in the BMI. Relative to REE there was an increase of basal metabolic rate (BMR) in both groups after one year. The sub-group DMPA that gained < 3 kg had increased significant weight, BMI and body surface (BS) with respiratory quotient (RQ) reduction, while the sub-group that gained ≥ 3 kg had a significant increase in weight, BMI, BS, fat-free mass, fat mass, BMR, Leptin, HOMA-IR and waist circumference, with RQ significantly reduced. Conclusion Our study found significant changes in weight, body composition and metabolic profile of the population studied in the first 12 months of contraceptive use. These changes mainly increased body weight, leptin levels and HOMA-IR which can contribute to the development of some chronic complications, including obesity, insulin resistance and diabetes mellitus.

[ effect of 8-weeks compound exercises training with omega-3 and l-carnitine supplementation intake on serum levels of visfatin in type 2 diabetic women]

Introduction: The aim of this study was to investigate the effect of 8 weeks of compound exercises with simultaneous omega-3 and l-carnitine supplementation on serum levels of Visfatin in type II Diabetic Women

Materials and Methods: This quasi-experimental study included a pretest and post-test with 5 experimental groups and one control group. Participants of the study were type II diabetic women, average age 52.7 +/- 1.6 years and body mass index 29.82 +/- 4.35 kg/m[2], who were randomly divided into 6 groups of 10 individuals each: 1. Exercise+placebo 2. Exercise+omega-3, 3. Exercise+L carnitine, 4. Exercise+ omega 3+ L- carnitine, 5. L-carnitine+omega-3 and 6. The control group. Omega-3 supplementation groups daily consumed 2000 mg of omega-3 and L-carnitine group 500 mg L-carnitine either. Training included 3 sessions per week, each session consisted of 30 minutes of aerobic exercise with 60-70% of maximum heart rate and 30-40 minute of circular resistance training with 60% of repetition maximum [1RM]

Results: T-test showed that visfatin levels in groups 3, 4 and 5 [p0.05

Conclusion: The results of this study, show that compound exercises, along with and simultaneous supplementation of Omega-3 and with l-carnitine, are appropriate stimuli to curtail visfatin levels and reduce risk factors in type 2 diabetic women

Association between nicotinamide phosphoribosyltransferase and de novo lipogenesis in nonalcoholic fatty liver disease

Objective: Jh//s study explored the association between serum nicotinamide phosphoribosyltransferase [NAMPT] and hepatic de novo lipogenesis [DNL] in nonalcoholic fatty liver disease [NAFLD] and determined whether or not this association is sex dependent

Subjects and Methods: In this cross-sectional study, 62 consecutive patients [32 males, 30 females] with NAFLD were recruited. Serum NAMPT [by ELI-SA], palmitic acid, and the DNL index of erythrocyte membranes as markers of hepatic DNL [by gas chromatography] were analyzed

The controlled attenuation parameter [CAP] and body impedance analyzer were used to assess hepatic and body fat respectively. Univariate and multiple linear regressions [to adjust for confounders] were used to analyze the association of serum NAMPT with palmitic acid, DNL index, CAP, and body fat

Results: The respective values of serum NAMPT [2.44 +/- 1.03 vs. 2.45 +/-1.13 ng/mL,p = 0.98], DNL index [3.11 [2.60-3.71 ] vs. 3.05 [2.40-3.59],p = 0.90], and pal-mitic acid [20.55% [15.34-24.04] vs. 22.64% [21.15-25.95], p = 0.07] were not significantly different between men and women, but those of CAP [326 [300-340] vs. 300 [261.25-329], p = 0.002] and body fat [37.71 +/- 3.80 vs. 26.60 +/- 5.70, p < 0.001] were significantly higher in women. In women, serum NAMPT had a significant negative association with the DNL index [p = -0.56, p = 0.01]. The DNL index also hada significant negative association with body fat [P = -0.46, p = 0.02]

In men, the only significant association was the positive association between serum NAMPT and CAP [p = 0.35, p = 0.035]

Conclusion: Higher serum NAMPT in women was associated with a lower hepatic DNL index, while in men it was associated with higher hepatic fat and had no association with the DNL index. Therefore, the serum NAMPT level interpretation for NAFLD prognosis is probably sex dependent

Meta-analysis of Circulating Adiponectin, Visfatin, and Ghrelin Levels in Patients with Systemic Lupus Erythematosus

OBJECTIVE: To evaluate the association between circulating adiponectin, visfatin, and ghrelin levels and systemic lupus erythematosus (SLE). METHODS: We conducted a meta-analysis to compare serum/plasma adiponectin, visfatin, and ghrelin levels in patients with SLE to those of healthy controls. RESULTS: Eleven articles (822 patients with SLE and 676 controls) were included in the meta-analysis. The meta-analysis showed that the adiponectin level was significantly higher in the SLE group than in the control group (standardized mean difference [SMD]=0.360, 95% confidence interval [CI]=0.025∼0.695, p=0.035). Stratification according to region showed that high adiponectin levels were associated with SLE in the Western population (SMD=0.225, 95% CI=0.024∼0.426, p=0.028), but not in the South American population. A subgroup analysis that adiponectin level is significantly higher in the SLE group than in the control after adjustment for age, sex, body mass index, large sample size (n>100); and mean age>40 years (SMD=0.492, 95% CI=0.065∼0.920, p=0.024; SMD=0.492, 95% CI=0.065∼0.920, p=0.024; SMD=0.429, 95% CI=0.124∼0.733, p=0.006, respectively). Stratification by region showed significantly increased visfatin and ghrelin levels in the SLE group in Western and South American populations. CONCLUSION: Our meta-analysis demonstrated that circulating adiponectin, visfatin, and ghrelin levels are significantly higher in SLE.

NAMPT enzyme activity regulates catabolic gene expression in gingival fibroblasts during periodontitis

Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues. NAMPT expression was also increased in lipopolysaccharide- and proinflammatory cytokine-stimulated primary cultured human gingival fibroblasts (GF). Adenovirus-mediated NAMPT (Ad-Nampt) overexpression upregulated the expression and activity of COX-2, MMP1 and MMP3 in human GF. The upregulation of IL-1β- or Ad-Nampt-induced catabolic factors was significantly abrogated by the intracellular NAMPT (iNAMPT) inhibitor, FK866 or by the sirtuin (SIRT) inhibitor, nicotinamide (NIC). Recombinant NAMPT protein or extracellular NAMPT (eNAMPT) inhibition using a blocking antibody did not alter NAMPT target gene expression levels. Moreover, intragingival Ad-Nampt injection mediated periodontitis-like phenotypes including alveolar bone loss in mice. SIRT2, a part of the SIRT family, was positively associated with NAMPT actions in human GF. Furthermore, in vivo inhibition of the NAMPT-NAD⁺-SIRT axis by NIC injection in mice ameliorated the periodontal inflammation and alveolar bone erosion caused by intragingival injection of Ad-Nampt. Our findings indicate that NAMPT is highly upregulated in human GF, while its enzymatic activity acts as a crucial mediator of periodontal inflammation and alveolar bone destruction via regulation of COX-2, MMP1, and MMP3 levels.