scholarly journals Visfatin: A Possible Role in Cardiovasculo-Metabolic Disorders

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2444
Author(s):  
Ali Dakroub ◽  
Suzanne A. Nasser ◽  
Nour Younis ◽  
Humna Bhagani ◽  
Yusra Al-Dhaheri ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Intracellular Signaling ◽  
Skeletal Muscles ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Signaling Cascades ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Enhancing Factor ◽  
Cell Colony

Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is an adipocytokine with several intriguing properties. It was first identified as pre-B-cell colony-enhancing factor but turned out to possess enzymatic functions in nicotinamide adenine dinucleotide biosynthesis, with ubiquitous expression in skeletal muscles, liver, cardiomyocytes, and brain cells. Visfatin exists in an intracellular (iNAMPT) and extracellular (eNAMPT) form. Intracellularly, visfatin/iNAMPT plays a regulatory role in NAD+ biosynthesis and thereby affects many NAD-dependent proteins such as sirtuins, PARPs, MARTs and CD38/157. Extracellularly, visfatin is associated with many hormone-like signaling pathways and activates some intracellular signaling cascades. Importantly, eNAMPT has been associated with several metabolic disorders including obesity and type 1 and 2 diabetes. In this review, a brief overview about visfatin is presented with special emphasis on its relevance to metabolic diseases. Visfatin/NAMPT appears to be a unique molecule with clinical significance with a prospective promising diagnostic, prognostic, and therapeutic applications in many cardiovasculo-metabolic disorders.

Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine

2008 ◽  
Vol 115 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Grit Sommer ◽  
Antje Garten ◽  
Stefanie Petzold ◽  
Annette G. Beck-Sickinger ◽  
Matthias Blüher ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
B Cell ◽  
Hormonal Regulation ◽  
Physiological Role ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Insulin Mimetic ◽  
Enzymatic Function ◽  
Enhancing Factor ◽  
Structure Regulation ◽  
Cell Colony

Over the last few years, it has become obvious that obesity and insulin resistance are linked by a variety of proteins secreted by adipocytes. Visfatin/PBEF (pre-B-cell colony-enhancing factor) has recently been identified as a novel adipokine with insulin-mimetic effects. Furthermore, an enzymatic function has been reported that reveals visfatin/PBEF as Nampt (nicotinamide phosphoribosyltransferase; EC 2.4.2.12.). Moreover, reports on the structure and hormonal regulation of visfatin/PBEF/Nampt have given further insights into its potential physiological role. The present review summarizes studies on visfatin/PBEF/Nampt as a novel adipokine.

scholarly journals Retinoic Acid Reduces Glucocorticoid Sensitivity in C2C12 Myotubes by Decreasing 11β-Hydroxysteroid Dehydrogenase Type 1 and Glucocorticoid Receptor Activities

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2700-2708 ◽  
Author(s):  
Evelyne M. Aubry ◽  
Alex Odermatt
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Glucose Tolerance ◽  
Glucocorticoid Receptor ◽  
Hormonal Regulation ◽  
Skeletal Muscles ◽  
Metabolic Diseases ◽  
Hydroxysteroid Dehydrogenase ◽  
C2c12 Myotubes

Vitamin A is a nutrient with remarkable effects on adipose tissue and skeletal muscles, and plays a role in controlling energy balance. Retinoic acid (RA), the carboxylic form of vitamin A, has been associated with improved glucose tolerance and insulin sensitivity. In contrast, elevated glucocorticoids have been implicated in the development of insulin resistance and impaired glucose tolerance. Here, we investigated whether RA might counteract glucocorticoid effects in skeletal muscle cells by lowering 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-dependent local glucocorticoid activation and/or activation of glucocorticoid receptor (GR). We found a dose-dependent down-regulation of 11β-HSD1 mRNA expression and activity upon incubation of fully differentiated mouse C2C12 myotubes with RA. In addition, RA inhibited GR transactivation by an 11β-HSD1-independent mechanism. The presence of RA during myogenesis did not prevent myotube formation but resulted in relatively glucocorticoid-resistant myotubes, exhibiting very low 11β-HSD1 expression and GR activity. The use of selective retinoic acid receptor (RAR) and retinoid X receptor ligands provided evidence that these effects were mediated through RARγ. Importantly, short hairpin RNA against RARγ abolished the effect of RA on 11β-HSD1 and GR. In conclusion, we provide evidence for an important role of RA in the control of glucocorticoid activity during myogenesis and in myotubes. Disturbances of the nutrient and hormonal regulation of glucocorticoid action in skeletal muscles might be relevant for metabolic diseases.

A Review on Visfatin/Nicotinamide Phosphoribosyltransferase/Pre-B Cell Colony-Enhancing Factor

2019 ◽  
Vol 10 (11) ◽  
pp. 2803
Author(s):  
Jayamathi Govindaraj ◽  
Keerthidaa Govindaraj ◽  
S. Raghavendra Jayesh ◽  
Kesavaram Padmavathy ◽  
U. Vidyarekha
Keyword(s):  
B Cell ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Enhancing Factor ◽  
Cell Colony

scholarly journals Toll-like receptors activation, signaling, and targeting: an overview

2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Salwa Refat El-Zayat ◽  
Hiba Sibaii ◽  
Fathia A. Mannaa
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Inflammatory Diseases ◽  
Host Cells ◽  
Signaling Cascades ◽  
Innate Immune Responses ◽  
Toll Like Receptors ◽  
Tlr Signaling ◽  
Dying Cells

Abstract Background Toll-like receptors (TLRs) are an important family of receptors that constitute the first line of defense system against microbes. They can recognize both invading pathogens and endogenous danger molecules released from dying cells and damaged tissues and play a key role in linking innate and adaptive immunity. TLRs are widely distributed in both immune and other body cells. The expressions and locations of TLRs are regulated in response to specific molecules derived from pathogens or damaged host cells. The binding of ligands to TLR activates specific intracellular signaling cascades that initiate host defense reactions. Such binding is ligand-dependent and cell type-dependent and leads to production of pro-inflammatory cytokines and type 1 interferon. TLR-dependent signaling pathways are tightly increased during innate immune responses by a variety of negative regulators. Overactivation of TLRs can ultimately lead to disruption of immune homeostasis and thus increase the risk for inflammatory diseases and autoimmune disorders. Antagonists/inhibitors targeting the TLR signaling pathways have emerged as novel therapeutics to treat these diseases. Aim of work The present review summarizes the structure, characterizations, and signaling of TLRs and their regulators, as well as describes the implication of TLRs in many diseases with a brief idea about the inhibitors that target TLR signaling pathways. Conclusion We conclude that TLRs are the main elements of our immune system, and they should be maintained functioning to keep the integrity of innate immunity. Targeting of TLR signaling represents a new challenge for treatment of many diseases.

scholarly journals IP3R-driven increases in mitochondrial Ca2+ promote neuronal death in NPC disease

2021 ◽  
Vol 118 (40) ◽  
pp. e2110629118
Author(s):  
Scott A. Tiscione ◽  
Maria Casas ◽  
Jonathan D. Horvath ◽  
Vincent Lam ◽  
Keiko Hino ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Intracellular Signaling ◽  
Signaling Cascades ◽  
Presenilin 1 ◽  
Signaling Cascade ◽  
Molecular Pathways ◽  
Loss Of Function ◽  
Signaling Axis ◽  
Niemann Pick

Ca2+ is the most ubiquitous second messenger in neurons whose spatial and temporal elevations are tightly controlled to initiate and orchestrate diverse intracellular signaling cascades. Numerous neuropathologies result from mutations or alterations in Ca2+ handling proteins; thus, elucidating molecular pathways that shape Ca2+ signaling is imperative. Here, we report that loss-of-function, knockout, or neurodegenerative disease–causing mutations in the lysosomal cholesterol transporter, Niemann-Pick Type C1 (NPC1), initiate a damaging signaling cascade that alters the expression and nanoscale distribution of IP3R type 1 (IP3R1) in endoplasmic reticulum membranes. These alterations detrimentally increase Gq-protein coupled receptor–stimulated Ca2+ release and spontaneous IP3R1 Ca2+ activity, leading to mitochondrial Ca2+ cytotoxicity. Mechanistically, we find that SREBP-dependent increases in Presenilin 1 (PS1) underlie functional and expressional changes in IP3R1. Accordingly, expression of PS1 mutants recapitulate, while PS1 knockout abrogates Ca2+ phenotypes. These data present a signaling axis that links the NPC1 lysosomal cholesterol transporter to the damaging redistribution and activity of IP3R1 that precipitates cell death in NPC1 disease and suggests that NPC1 is a nanostructural disease.

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