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https://www.readbyqxmd.com/read/29146412/skeletal-muscle-overexpression-of-nicotinamide-phosphoribosyl-transferase-in-mice-coupled-with-voluntary-exercise-augments-exercise-endurance
#1
Sheila R Costford, Bram Brouwers, Meghan E Hopf, Lauren M Sparks, Mauro Dispagna, Ana P Gomes, Heather H Cornnell, Chris Petucci, Peter Phelan, Hui Xie, Fanchao Yi, Glenn A Walter, Timothy F Osborne, David A Sinclair, Randall L Mynatt, Julio E Ayala, Stephen J Gardell, Steven R Smith
OBJECTIVE: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD(+)), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding...
November 6, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29132311/weighted-gene-co-expression-network-analysis-of-expression-data-of-monozygotic-twins-identifies-specific-modules-and-hub-genes-related-to-bmi
#2
Weijing Wang, Wenjie Jiang, Lin Hou, Haiping Duan, Yili Wu, Chunsheng Xu, Qihua Tan, Shuxia Li, Dongfeng Zhang
BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. RESULTS: In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29125463/pharmacological-augmentation-of-nicotinamide-phosphoribosyltransferase-nampt-protects-against-paclitaxel-induced-peripheral-neuropathy
#3
Peter M LoCoco, April L Risinger, Hudson R Smith, Teresa S Chavera, Kelly A Berg, William P Clarke
Chemotherapy-induced peripheral neuropathy (CIPN) arises from collateral damage to peripheral afferent sensory neurons by anticancer pharmacotherapy, leading to debilitating neuropathic pain. No effective treatment for CIPN exists, short of dose-reduction which worsens cancer prognosis. Here we report that stimulation of nicotinamide phosphoribosyltransferase (NAMPT) produced robust neuroprotection in an aggressive CIPN model utilizing the frontline anticancer drug, paclitaxel (PTX). Daily treatment of rats with the first-in-class NAMPT stimulator, P7C3-A20, prevented behavioral and histologic indicators of peripheral neuropathy, stimulated tissue NAD recovery, improved general health, and abolished attrition produced by a near maximum-tolerated dose of PTX...
November 10, 2017: ELife
https://www.readbyqxmd.com/read/29104667/promotion-of-anoxia-reoxygenation-induced-inflammation-and-permeability-enhancement-by-nicotinamide-phosphoribosyltransferase-activated-mapk-signaling-in-human-umbilical-vein-endothelial-cells
#4
Nao Yan, Wei Yang, Xiao Dong, Qiao Fang, Yi Gong, Jian-Liang Zhou, Jian-Jun Xu
Previous studies have demonstrated that nicotinamide phosphoribosyltransferase (NAMPT) promoted inflammation and permeability of vascular endothelial cells following cardiopulmonary bypass (CPB). In addition, mitogen-activated protein kinase (MAPK) signaling was activated and contributed to these cell responses. However, the mechanism by which NAMPT regulates cellular inflammation and permeability remains unknown, and whether NAMPT regulates MAPK signaling during this process is also not clear. The present study established an anoxia-reoxygenation (A-R) model using human umbilical vein endothelial cells (HUVECs) and investigated the regulation of MAPK signaling by NAMPT by using small RNA transfection, ELISA and western blot analysis...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29104634/endogenous-nampt-upregulation-is-associated-with-diabetic-nephropathy-inflammatory-fibrosis-through-the-nf-%C3%AE%C2%BAb-p65-and-sirt1-pathway-nmn-alleviates-diabetic-nephropathy-inflammatory-fibrosis-by-inhibiting-endogenous-nampt
#5
Ye Chen, Yuzhen Liang, Tingting Hu, Riming Wei, Congjie Cai, Ping Wang, Lingyu Wang, Wei Qiao, Leping Feng
Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD(+)) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29101068/association-of-genetic-variants-in-retn-nampt-and-adipoq-gene-with-glycemic-metabolic-traits-and-diabetes-risk-in-a-chinese-population
#6
Qiang Zhou, Bo Chen, Tianxing Ji, Miaoshan Luo, Jiandong Luo
Abnormal serum levels of adipokine have been established to be a strong predictor of developing several human diseases including type 2 diabetes mellitus (T2DM). Association studies have reported several genetic variants in genes coding adipokines with contributions to T2DM susceptibility as well as some glycemic and metabolic traits, of which the single nucleotide polymorphisms (SNPs) of RETN, NAMPT, and ADIPOQ gene were well documented. However, little is known about contributions of these SNPs to above phenotypes in Chinese...
October 31, 2017: Gene
https://www.readbyqxmd.com/read/29100430/novel-naprt-specific-antibody-identifies-small-cell-lung-cancer-and-neuronal-cancers-as-promising-clinical-indications-for-a-nampt-inhibitor-niacin-co-administration-strategy
#7
Jonathan Cole, Marie-Christine Guiot, Michel Gravel, Cynthia Bernier, Gordon C Shore, Anne Roulston
Tumor cells are particularly dependent on NAD(+) due to higher rates of metabolism, DNA synthesis and repair. Nicotinamide phosphoribosyltransferase inhibitors (NAMPTis) inhibit NAD(+) biosynthesis and represent promising new anti-cancer agents. However, clinical efficacy has been limited by toxicities demonstrating the need for drug combinations to broaden the therapeutic index. One potential combination involves niacin/NAMPTi co-administration. Niacin can rescue NAD(+) biosynthesis through a parallel pathway that depends on nicotinic acid phosphoribosyltransferase (NAPRT) expression...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29079670/the-levels-of-adipokines-and-hormonal-changes-during-the-menstrual-cycle-in-normal-weight-women
#8
Katarzyna Wyskida, Grzegorz Franik, Tomasz Wikarek, Aleksander Owczarek, Alham Delroba, Jerzy Chudek, Jerzy Sikora, Magdalena Olszanecka-Glinianowicz
CONTEXT: The aim of this study was to assess plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 levels in relation to hormonal changes during the menstrual cycle in young, healthy, normal-weight women. METHODS: The study involved 52 young, healthy, normal-weight women. Anthropometric parameters, body composition and levels of plasma leptin, adiponectin, resistin, visfatin/NAMPT, omentin-1, vaspin, apelin, TNF-α, IL-6 and RBP4 in addition to serum FSH, LH, estradiol, progesterone, 17-OH progesterone, androgens, SHBG and insulin concentrations were measured during a morning in fasting state three times: between days 2-4, days 12-14 and days 24-26 of the menstrual cycle...
October 27, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29059722/genome-wide-association-study-reveals-genetic-loci-and-candidate-genes-for-average-daily-gain-in-duroc-pigs
#9
Jianping Quan, Rongrong Ding, Xingwang Wang, Ming Yang, Yang Yang, Enqin Zheng, Ting Gu, Gengyuan Cai, Zhenfang Wu, Dewu Liu, Jie Yang
Objective: Average daily gain (ADG) is an important target trait of pig breeding programs. We aimed to identify single nucleotide polymorphisms (SNPs) and genomic regions that are associated with ADG in the Duroc pig population. Methods: We performed a genome-wide association study involving 390 Duroc boars and by using the PorcineSNP60K Beadchip and two linear models. Results: After quality control, we detected 35971 SNPs, which included seven SNPs that are significantly associated with the ADG of pigs...
October 20, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29054982/discovery-of-a-highly-selective-nampt-inhibitor-that-demonstrates-robust-efficacy-and-improved-retinal-toxicity-with-nicotinic-acid-co-administration
#10
Genshi Zhao, Colin F Green, Yu-Hua Hui, Lourdes Prieto, Robert Shepard, Sucai Dong, Tao Wang, Bo Tan, Xueqian Gong, Lisa Kays, Robert L Johnson, Wenjuan Wu, Shobha Bhattachar, Miriam Del Prado, James R Gillig, Maria-Carmen Fernandez, Ken D Roth, Sean Buchanan, Ming-Shang Kuo, Sandaruwan Geeganage, Timothy P Burkholder
NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as an anti-cancer target for developing potential novel therapeutics. Several NAMPT inhibitors have been discovered, some of which have been subjected to clinical investigations. Yet, the on-target hematological and retinal toxicities have hampered their clinical development. In this study, we report the discovery of a unique NAMPT inhibitor, LSN3154567. This molecule is highly selective, and has a potent and broad spectrum of anti-cancer activity...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29054583/dietary-resveratrol-increases-mid-life-fecundity-of-female-nothobranchius-guentheri
#11
Youngjoo Lee, Andrew C Drake, Nicholas O Thomas, Lindsey G Ferguson, Patrick E Chappell, Kate Petersen Shay
The decline of female reproductive function is an early phenotype of aging in humans, occurring only midway through the lifespan. Yet the number of women delaying pregnancy continues to rise in industrialized societies due to personal or socioeconomic circumstances, often resulting in subfertility or difficulty conceiving. There are few defined mechanisms associated with this etiology, and equally few effective therapies. To combat this problem, we used a novel emerging model, Nothobranchius guentheri, that recapitulates the age-associated spectrum of changes that adversely affect human fertility...
October 17, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29049890/dna-methylation-signatures-in-peripheral-blood-mononuclear-cells-from-a-lifestyle-intervention-for-women-at-midlife-a-pilot-rct
#12
Lisa M McEwen, Evan G Gatev, Meaghan J Jones, Julia L MacIsaac, Megan M McAllister, Rebecca E Goulding, Kenneth M Madden, Martin G Dawes, Michael S Kobor, Maureen C Ashe
OBJECTIVES: Physical activity confers many health benefits, but the underlying mechanisms require further exploration. In this pilot randomized controlled trial we tested the association between longitudinal measures of DNA methylation and changes in objective measures including physical activity, weight loss, and C-reactive protein levels in community-dwelling women aged 55 to 70 years. METHODS: We assessed DNA methylation from 20 healthy post-menopausal women (55-70 years of age), who did not have a mobility disability and allocated them to a group-based intervention, Everyday Activity Supports You (EASY), or a control group (monthly group-based health-related education sessions)...
October 19, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29029387/the-%C3%AE-nad-salvage-pathway-and-pkc-mediated-signaling-influence-localized-parp-1-activity-and-ctcf-poly-adp-ribosylation
#13
David J P Henderson, Jj L Miranda, Beverly M Emerson
Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is critical for CTCF-dependent regulation of chromatin boundary and insulator elements. Loss of CTCF PARylation results in epigenetic silencing of certain tumor suppressor genes through destabilization of nearby chromatin boundaries. We investigated the metabolic and mechanistic processes that regulate PARP-1-mediated CTCF PARylation in human cancer cell lines and discovered a key role for the expression and activity of β-NAD+ salvage enzymes, NAMPT and NMNAT-1...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974242/oleate-ameliorates-palmitate-induced-reduction-of-nampt-activity-and-nad-levels-in-primary-human-hepatocytes-and-hepatocarcinoma-cells
#14
Melanie Penke, Susanne Schuster, Theresa Gorski, Rolf Gebhardt, Wieland Kiess, Antje Garten
BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) levels are crucial for liver function. The saturated fatty acid palmitate and the unsaturated fatty acid oleate are the main free fatty acids in adipose tissue and human diet. We asked how these fatty acids affect cell survival, NAMPT and NAD levels in HepG2 cells and primary human hepatocytes. METHODS: HepG2 cells were stimulated with palmitate (0.5mM), oleate (1mM) or a combination of both (0...
October 3, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28956002/maternal-resveratrol-intake-during-lactation-attenuates-hepatic-triglyceride-and-fatty-acid-synthesis-in-adult-male-rat-offspring
#15
Masato Tanaka, Tomomi Kita, Shojiro Yamasaki, Tae Kawahara, Yukako Ueno, Mai Yamada, Yuuka Mukai, Shin Sato, Masaaki Kurasaki, Takeshi Saito
Resveratrol (3,5,4-trihydroxystilbene) is a natural polyphenolic compound found in grapes and red wine and has been shown to exert protective effects on the liver preventing lipid accumulation induced by a high-fat diet. However, no studies have shown that the nutritional resveratrol intake by the parental generation has modified lipogenesis in an adult offspring. The aim of this study was to investigate whether maternal resveratrol intake during lactation affects lipogenesis in adult male rat offspring, and if it does, what is the molecular mechanistic basis...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28941575/bioenergetic-adaptations-of-the-human-liver-in-the-alpps-procedure-how-liver-regeneration-correlates-with-mitochondrial-energy-status
#16
Henrique Alexandrino, Anabela Rolo, João S Teodoro, Henrique Donato, Ricardo Martins, Marco Serôdio, Mónica Martins, José G Tralhão, Filipe Caseiro Alves, Carlos Palmeira, Francisco Castro E Sousa
BACKGROUND: The Associating Liver Partition and Portal Ligation for Staged Hepatectomy (ALPPS) depends on a significant inter-stages kinetic growth rate (KGR). Liver regeneration is highly energy-dependent. The metabolic adaptations in ALPPS are unknown. AIMS: i) Assess bioenergetics in both stages of ALPPS (T1 and T2) and compare them with control patients undergoing minor (miHp) and major hepatectomy (MaHp), respectively; ii) Correlate findings in ALPPS with volumetric data; iii) Investigate expression of genes involved in liver regeneration and energy metabolism...
September 20, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28934431/genetic-profiling-and-comorbidities-of-zika-infection
#17
Mohammad Ali Moni, Pietro Lio'
Background: The difficulty in distinguishing infection by Zika virus (ZIKV) from other flaviviruses is a global health concern, particularly given the high risk of neurologic complications (including Guillain-Barré syndrome [GBS]) with ZIKV infection. Methods: We developed quantitative frameworks to compare and explore infectome, diseasome, and comorbidity of ZIKV infections. We analyzed gene expression microarray and RNA-Seq data from ZIKV, West Nile fever (WNF), chikungunya, dengue, yellow fever, Japanese encephalitis virus, GBS, and control datasets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28919418/the-nampt-e2f2-sirt1-axis-promotes-proliferation-and-inhibits-p53-dependent-apoptosis-in-human-melanoma-cells
#18
Hailong Zhao, Weiwei Tang, Xiaowen Chen, Siyu Wang, Xianyan Wang, Haiyan Xu, Lijuan Li
Melanoma is the most common primary malignant neoplasm in adults, causing more deaths than any other skin cancer, necessitating the development of new target-based approaches. Current evidence suggests SIRT1, the mammalian nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD(+) biosynthetic enzyme, together comprise a novel systemic regulatory network to play a pivotal role in cell proliferation and apoptosis. Nevertheless, how the regulation of this cofactor interfaces with signal transduction network remains poorly understood in melanoma...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28915567/melatonin-inhibits-sirt1-dependent-nampt-and-nfat5-signaling-in-chondrocytes-to-attenuate-osteoarthritis
#19
Jia Yi Guo, Feng Li, Yong Bing Wen, Hong Xun Cui, Ma Long Guo, Lin Zhang, Yun Fei Zhang, Yan Jin Guo, Yan Xing Guo
Osteoarthritis (OA) is a degenerative joint disease mainly characterized by cartilage degradation. Interleukin-1β (IL-1β) contributes to OA pathogenesis by enhancing oxidative stress and inflammation. Melatonin reportedly elicits potent protection against OA. However, the role of melatonin and underlying mechanism in IL-1β-stimulated chondrocytes remain largely unclear. In this study, we found that melatonin inhibited IL-1β-induced toxicity and sirtuin 1 (Sirt1) enhancement in human chondrocytes. Melatonin reduced the IL-1β-increased nicotinamide phosphoribosyltransferase (NAMPT) expression and the NAD(+) level in chondrocytes in a Sirt1-dependent manner...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904384/targeting-the-vulnerability-to-nad-depletion-in-b-cell-acute-lymphoblastic-leukemia
#20
S Takao, W Chien, V Madan, D-C Lin, L-W Ding, Q-Y Sun, A Mayakonda, M Sudo, L Xu, Y Chen, Y-Y Jiang, S Gery, M Lill, E Park, W Senapedis, E Baloglu, M Müschen, H P Koeffler
Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase that regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD) that plays a vital role in energy metabolism...
September 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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