1.Research advances on the roles of nicotinamide phosphoribosyltransferase in inflammation.
Jing HUANG ; Er-qing WEI ; Yun-bi LU ;
Journal of Zhejiang University. Medical sciences 2014;43(2):234-239
Nicotinamide phosphoribosyltransferase (Nampt) is also called visfatin or pre-B-cell colony-enhancing factor. The functions of Nampt have been reported as a cytokine, an adipokine and the rate-limiting enzyme in nicotinamide adenine dinucleotide biosynthesis. As a pleiotropic multifunctional protein, Nampt is involved in a variety of physiological and pathological conditions including innate immunity, metabolic disorders, and stress; and Nampt also participates in inflammatory disorders such as acute lung injury, atherosclerosis, myocardial infarct, obesity, type 2 diabetes, and rheumatoid arthritis. The studies indicate that Nampt might be a potential target for pharmacological intervention against inflammatory diseases. We review research advances on the roles of Nampt in inflammation.
Animals
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Humans
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Inflammation
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enzymology
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Nicotinamide Phosphoribosyltransferase
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metabolism
2.Nicotinamide phosphoribosyltransferase and its roles in cancer.
Journal of Zhejiang University. Medical sciences 2014;43(1):109-114
Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme for synthesis of nicotinamide adenine dinucleotide in mammalian cells. Recent studies show that Nampt also works as a cytokine that exerts insulin-mimetic effects by binding to the insulin receptor, induces B-cell differentiation, inhibits neutrophil apoptosis, and affects immune and inflammatory functions. This review is focused on current knowledge regarding the structure and function of Nampt and its roles in carcinogenesis.
Humans
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Neoplasms
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enzymology
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Nicotinamide Phosphoribosyltransferase
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metabolism
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physiology
3.Advances in the proinflammatory effects of visfatin and its relationship with diabetic kidney disease.
Acta Academiae Medicinae Sinicae 2015;37(2):246-252
Visfatin, also known as the pre-B-cell colony enhancing factor, is a new member of the adipocytokines. It serves as a nicotinamide phosphoribosyltransferase in cells. Visfatin has complex biological functions and may be involved in the pathogenesis of diabetic kidney disease; it may contribute to the chronic inflammatory status at systemic and renal levels and thus aggravate renal injury. Further research on visfatin will provide new insights in the treatment of diabetic kidney disease. This article reviews the recent advances in the proinflammatory effects of visfatin and its relationship with diabetic kidney disease.
Cytokines
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Diabetic Nephropathies
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Humans
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Nicotinamide Phosphoribosyltransferase
4.Meta-analysis of Circulating Adiponectin, Visfatin, and Ghrelin Levels in Patients with Systemic Lupus Erythematosus.
Journal of Rheumatic Diseases 2017;24(2):99-107
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.
Adiponectin*
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Body Mass Index
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Ghrelin*
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Humans
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Lupus Erythematosus, Systemic*
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Nicotinamide Phosphoribosyltransferase*
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Sample Size
5.A method based on endogenous fluorescence determination for screening NAMPT inhibitors.
Xue HAN ; Xue DONG ; Wen-xue JIANG ; Peng HUANG ; Wei-ping ZHANG ; Chun TANG
Journal of Zhejiang University. Medical sciences 2014;43(3):319-326
OBJECTIVETo establish a method for screening nicotinamide phosphoribosyl transferase (NAMPT) inhibitors based on endogenous fluorescence determination.
METHODSThe double mutants of NAMPT, G355C/D393C, was cross-linked by using 1, 4-Bismaleimidobutane (BMB) to block the entrance of enzymatic active site of NAMPT. The binding of compounds to NAMPT was evaluated according to the change of spontaneous fluorescence of NAMPT and BMB-NAMPT with 280 nm excitation and 333 nm emmision. The in vitro enzamatic activity of NAMPT was determined by nuclear magnetic resonance. The cell viability was determined by MTT assay.
RESULTSFK866 significantly decreased the spontaneous fluorescence of NAMPT but not of BMB-NAMPT. Rosmaric, cynarine and 1, 3-dicaffeoylquinic acid also decreased the spontaneous fluorescence of both NAMPT and BMB-NAMPT. However, the inhibition on two proteins was equivalent. FK866 significantly inhibit the catalysis of NAMPT. Rosmarinic acid, cynarine and 1, 3-dicaffeoylquinic acid failed to inhibit the catalysis of NAMPT. FK866 inhibited the viability of A549 cells, but rosmarinic acid, cynarine and 1, 3-dicaffeoylquinic acid did not.
CONCLUSIONEndogenous fluorescence spectrometry based on NAMPT and BMB-NAMPT protein can be used for screening compounds that bind with NAMPT, and distinguishing the binding site - either within the enzymatic active site or not. Rosmarinic acid, cynarine and 1, 3-dicoffeoylquinic acid can bind to NAMPT out its enzymatic active site.
Apoptosis ; drug effects ; Cell Line, Tumor ; Drug Evaluation, Preclinical ; methods ; Fluorescence ; Humans ; Nicotinamide Phosphoribosyltransferase ; antagonists & inhibitors
6.Research progress on nicotinamide phosphoribosyl transferase involved in aging and age-related diseases.
Journal of Zhejiang University. Medical sciences 2011;40(6):680-684
Nicotinamide phosphoribosyl transferase (NAMPT) is the key enzyme for the synthesis of nicotinamide adenine dinucleotide (NAD), and also serves as a cytokine in mammalian cells. NAMPT is known to participate in biological responses such as glucose metabolism, inflammatory response and stress. Recent studies have revealed that NAMPT is closely associated with aging and age-related diseases such as diabetes, obesity, cancers, neuronal degeneration and cardiovascular diseases. Research on NAMPT may provide insight on prevention and treatment of related diseases.
Aging
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metabolism
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physiology
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Animals
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Humans
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Neoplasms
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metabolism
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physiopathology
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Nerve Degeneration
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metabolism
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physiopathology
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Nicotinamide Phosphoribosyltransferase
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metabolism
;
physiology
7.Expression of NAMPT in Patients with Multiple Myeloma and Its Correlation with Clinical Manifestation.
Journal of Experimental Hematology 2023;31(3):769-776
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.
Humans
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Multiple Myeloma/genetics*
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Nicotinamide Phosphoribosyltransferase
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Prognosis
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RNA, Messenger/genetics*
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Treatment Outcome
8.Effects of visfatin gene polymorphisms on glycolipid metabolism and exercise-induced weight reduction in obesity.
Acta Physiologica Sinica 2012;64(1):96-100
Visfatin, also named nicotinamide phosphoribosyl transferase (NAMPT), is a cytokine secreted from adipose tissue. Visfatin can regulate immune action and is involved in the NAD+ salvage pathway. In addition, recent researches have shown that visfatin helps the regulation of glucose and lipid metabolism, especially in exercise-induced weight reduction for obesity. The aim of this review is to provide an overview of the contribution of visfatin gene polymorphisms to glucose and lipid metabolism and exercise-induced weight reduction in obesity.
Exercise
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physiology
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Glycolipids
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metabolism
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Humans
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Nicotinamide Phosphoribosyltransferase
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genetics
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physiology
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Obesity
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genetics
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metabolism
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Polymorphism, Genetic
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Weight Loss
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genetics
9.Effects of visfatin and metformin on insulin resistance and reproductive endocrine in rats with polycystic ovary syndrome.
Tiansong ZHANG ; Xianxiang ZOU ; Shujun SU ; Tian LI ; Jing WAN ; Jian GU
Journal of Southern Medical University 2014;34(9):1314-1318
OBJECTIVETo investigate the therapeutical effects of visfatin and metformin on insulin resistance and reproductive endocrine disorder in rats with polycystic ovary syndrome (PCOS).
METHODSForty female Wistar rats were divided into 4 equal groups, and in groups A, B and C, the rats were injected subcutaneously with dehydroepiandrosterone (DHEA) for PCOS modeling, with group D as the blank control injected with soybean oil. Vaginal smears and serological testing were taken to assess the modeling. After the modeling, the rats in group A received 10 µg reorganized visfatin injection and those in group B were treated with metformin (14 mg/100 g) on a daily basis for 15 days. Serum levels of T, LH, FSH, FINS and blood glucose levels during OGTT were measured before and after the treatments, and HOMA-IR and LH to FSH ratio were calculated. The ovaries were then dissected for pathological examination.
RESULTSIn groups A and B, FINS, FPG, T, HOMA-IR and blood glucose levels during OGTT were significantly decreased after the treatments (P<0.05), which resulted in recovery of regular menses in 8 (80%) rats in group A and 7 (77.8%) rats in group B with the development of normal follicles. Visfatin and metformin produced equivalent therapeutic effects in improving the insulin resistance and hyperandrogenism in PCOS rats.
CONCLUSIONVisfatin and metformin have equivalent therapeutic effects in improving insulin resistance and hyperandrogenism and in promoting the recovery of regular menses and development of normal follicles in PCOS rats.
Animals ; Female ; Humans ; Insulin Resistance ; Metformin ; pharmacology ; Nicotinamide Phosphoribosyltransferase ; pharmacology ; Polycystic Ovary Syndrome ; complications ; drug therapy ; Rats ; Rats, Wistar
10.The Effect of Vildagliptin on Visfatin in Korean Patients with Type 2 Diabetes: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Prospective Study.
Young Hwan JANG ; Dong Hyun IN ; Jae Kook YANG ; Hyuk Jin MOON ; Gyu Tae YOON ; Ah Jeong RYU ; Yeo Joo KIM ; Eun Young LEE ; Hyun Jin KIM ; Bon Jeong KU ; Jae Min LEE ; Kang Seo PARK ; In Suk LEE ; Jong Min LEE ; Dong Mee LIM ; Keun Yong PARK ; Sang Jin KIM
Journal of Korean Diabetes 2015;16(4):303-309
BACKGROUND: The effects of dipeptidyl peptidase-4 inhibitors on adipokines remain obscure. The aim of this study was to evaluate the effect of the addition of vildagliptin on visfatin, an adipokine that represents inflammatory biomarkers of adipose tissue, in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy. METHODS: In this 16-week, double-blind, randomized, parallel-group, placebo-controlled study, 71 patients were randomly assigned to vildagliptin 50 mg twice a day (n = 35) or placebo (n = 36) added to ongoing metformin therapy. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma lipids, and visfatin levels were measured at baseline and 16 weeks after treatment. RESULTS: After 16 weeks, significant reduction in HbA1c and FPG was observed with vildagliptin addon treatment compared to placebo (-0.54 +/- 0.52%, P = 0.001 and -14.80 +/- 19.21 mg/dL, P = 0.004, respectively). However, no other clinically meaningful changes in lipid parameters or visfatin were observed. CONCLUSION: Vildagliptin add-on to metformin significantly improved fasting blood glucose and HbA1c. However, in this study, no significant differences in lipid parameters or visfatin level were observed between the two groups.
Adipokines
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Adipose Tissue
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Biomarkers
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Blood Glucose
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Diabetes Mellitus
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Fasting
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Hemoglobin A, Glycosylated
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Humans
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Metformin
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Nicotinamide Phosphoribosyltransferase*
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Plasma
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Prospective Studies*