A Visfatin Promoter Polymorphism Is Associated with Low‐Grade Inflammation and Type 2 Diabetes

Zhang, Xu Dong; Gottardo, Lucia; Thompson, Rachel; Powers, Christine; Nolan, D.; Duffy, Jill; Marescotti, Maria Cristina; Avogaro, Angelo; Doria, Alessandro

doi:10.1038/oby.2006.247

Cited by 67 publications

(61 citation statements)

References 27 publications

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“…Although this study was retracted in 2007 due to numerous scientific flaws, the original observation was supported by a number of subsequent studies demonstrating that plasma visfatin levels in humans correlate with obesity, visceral fat mass, type 2 diabetes, and presence of the metabolic syndrome (171)(172)(173). Furthermore, visfatin promoter SNPs were reported to be associated with fasting glucose and insulin levels, as well as type 2 diabetes (174,175). Other studies, however, did not confirm an association of visfatin and visceral adipose tissue or parameters of insulin sensitivity in humans and rodents (176)(177)(178)(179).…”

Section: Visfatin/pbef/namptmentioning

confidence: 74%

Adipokines and Insulin Resistance

Rabe¹,

Lehrke²,

Parhofer³

et al. 2008

Mol Med

685

480

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Obesity is associated with an array of health problems in adult and pediatric populations. Understanding the pathogenesis of obesity and its metabolic sequelae has advanced rapidly over the past decades. Adipose tissue represents an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) that signal to organs of metabolic importance including brain, liver, skeletal muscle, and the immune systemthereby modulating hemostasis, blood pressure, lipid and glucose metabolism, inflammation, and atherosclerosis. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones adiponectin, chemerin, leptin, omentin, resistin, retinol binding protein 4, tumor necrosis factor-α and interleukin-6, vaspin, and visfatin on insulin resistance. LRb is restricted to the hypothalamus, brainstem and key regions of the brain which control feeding, energy balance and glucose metabolism.c Effects likely to be mediated through inhibition of a yet-unknown protease.d Effects mediated through nicotinamide adenine dinucleotide biosynthetic activity.

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Section: Visfatin/pbef/namptmentioning

confidence: 74%

Adipokines and Insulin Resistance

Rabe¹,

Lehrke²,

Parhofer³

et al. 2008

Mol Med

685

480

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“…Chronic low-grade inflammation constitutes a mediator in the development of obesity-related diseases. The association of NAMPT with other inflammatory markers, such as MCP-1 and PAI-1 antigen [57] together with its increased production and release by macrophages [28,58] supports its pro-inflammatory properties [59]. Furthermore, a strong association between NAMPT and TNF-a and IL-8 in PBC has been described [39,46,58].…”

Section: Discussionmentioning

confidence: 88%

Association of increased Visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity

Catalán

Gómez-Ambrosi

Rodríguez

et al. 2010

Nutrition, Metabolism and Cardiovascular Diseases

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Background and aims: Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine with physiological effects on the control of glucose homeostasis as well as potentially involved in inflammation. The association of circulating NAMPT concentrations with obesity has not been clearly established. The aim of the present work was to evaluate the effect of obesity on circulating concentrations and gene expression levels of NAMPT in human peripheral blood cells (PBCs) as well as its involvement in inflammation, glucose and lipid metabolism.

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“…Our studies identified two ARDSassociated NAMPT promoter SNPs (22,422A/G and 2948G/T), and, despite study limitations, including relatively small groups of patients with ARDS and controls and lack of cross validation in the two ARDS cohorts, our in vitro experiments confirmed robust and significant influence of these SNPs on NAMPT promoter activity in response to 18% CS challenge. Functionality of the 2948G/T (C/A) variant is supported by recent studies associating this NAMPT SNP with low-grade inflammation in patients with diabetes (31). Under static conditions, silencing of STAT5 failed to influence the activity of promoters with 22,422A/G or 2948G/T.…”

Section: Discussionmentioning

confidence: 90%

The NAMPT Promoter Is Regulated by Mechanical Stress, Signal Transducer and Activator of Transcription 5, and Acute Respiratory Distress Syndrome–Associated Genetic Variants

Sun¹,

Elangovan

Mapes³

et al. 2014

Am J Respir Cell Mol Biol

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Increased nicotinamide phosphoribosyltransferase (NAMPT) transcription is mechanistically linked to ventilator-induced inflammatory lung injury (VILI), with VILI severity attenuated by reduced NAMPT bioavailability. The molecular mechanisms of NAMPT promoter regulation in response to excessive mechanical stress remain poorly understood. The objective of this study was to define the contribution of specific transcription factors, acute respiratory distress syndrome (ARDS)-associated single nucleotide polymorphisms (SNPs), and promoter demethylation to NAMPT transcriptional regulation in response to mechanical stress. In vivo NAMPT protein expression levels were examined in mice exposed to high tidal volume mechanical ventilation. In vitro NAMPT expression levels were examined in human pulmonary artery endothelial cells exposed to 5 or 18% cyclic stretch (CS), with NAMPT promoter activity assessed using NAMPT promoter luciferase reporter constructs with a series of nested deletions. In vitro NAMPT transcriptional regulation was further characterized by measuring luciferase activity, DNA demethylation, and chromatin immunoprecipitation. VILI-challenged mice exhibited significantly increased NAMPT expression in bronchoalveolar lavage leukocytes and in lung endothelium. A mechanical stress-inducible region (MSIR) was identified in the NAMPT promoter from 22,428 to 22,128 bp. This MSIR regulates NAMPT promoter activity, mRNA expression, and signal transducer and activator of transcription 5 (STAT5) binding, which is significantly increased by 18% CS. In addition, NAMPT promoter activity was increased by pharmacologic promoter demethylation and inhibited by STAT5 silencing. ARDS-associated NAMPT promoter SNPs rs59744560 (2948G/T) and rs7789066 (22,422A/G) each significantly elevated NAMPT promoter activity in response to 18% CS in a STAT5-dependent manner. Our results show that NAMPT is a key novel ARDS therapeutic target and candidate gene with genetic/epigenetic transcriptional regulation in response to excessive mechanical stress.Keywords: acute respiratory distress syndrome; cyclic stretch; nicotinamide phosphoribosyltransferase; B cell colony-enhancing factor; signal transducer and activator of transcription 5 Clinical RelevanceNicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony-enhancing factor is a key novel molecular marker and therapeutic target for acute lung injury. This study promotes the interpretation of the genetic and epigenetic regulation of NAMPT in response to excessive mechanical stress.Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and a persistently high mortality rate (z 30%) (1, 2). Mechanical ventilation is a life-saving intervention in critically ill patients with respiratory failure due to ARDS; however, excessive mechanical ventilation contributes directly to inflammatory lung injury, a process known

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A Visfatin Promoter Polymorphism Is Associated with Low‐Grade Inflammation and Type 2 Diabetes

Cited by 67 publications

References 27 publications

Adipokines and Insulin Resistance

Adipokines and Insulin Resistance

Association of increased Visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity

The NAMPT Promoter Is Regulated by Mechanical Stress, Signal Transducer and Activator of Transcription 5, and Acute Respiratory Distress Syndrome–Associated Genetic Variants

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