Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
Hormonal regulation of visfatin gene in avian Leghorn male hepatoma (LMH) cells
Graphical abstract
Introduction
Visfatin or Nampt is an adipokine originally identified as a growth factor for early β cells and thereby called pre-β-cell colony-enhancing factor (PBEF) (Samal et al., 1994; Sethi and Vidal-Puig, 2005). Nampt has an intracellular (iNampt) and extracellular (eNampt) forms. iNampt is a nicotinamide phosphoribosyl transferase (Nampt), a cytosolic enzyme, involved in nicotinamide adenine dinucleotide (NAD) biosynthesis (Rongvaux et al., 2002). It regulates the activity of NAD-consuming enzymes such as sirtuins and affects several metabolic and stress processes (Hognogi and Simiti, 2016). Although the physiological roles of eNampt have been controversial and a matter of debate for decades, several studies have assigned to eNampt a cytokine function and thereby they named it “visfatin” which plays a key role in metabolic disorders (diabetes and obesity) via regulating glucose-stimulated insulin secretion and signaling (Dahl et al., 2007; Revollo et al., 2007; Song et al., 2008; Xie et al., 2007).
Visfatin was found to be expressed in several mammalian cell types and tissues including hepatocytes (Imai and Kiess, 2009) and has been shown to be regulated by various cytokines, hormones, and factors (Hector et al., 2007; MacLaren et al., 2007; Skrzypski et al., 2018; Tan et al., 2009; Zhang et al., 2019). Such studies are currently lacking in avian (non-mammalian) species.
Avian genetic selection for high growth rate and muscle enhancement has resulted in hyperphagic broilers that are prone to obesity. Modern broiler (meat-type) chickens consume over 4 kg of feed to achieve an average slaughter-weight of 2.8 kg in only 42 days. This body weight increase arises mainly from breast (pectoralis) muscle and abdominal fat (Hood, 1982; Scheuermann et al., 2003). Additionally, chickens are hyperglycemic compared to mammals, with their plasma glucose levels averaging three times that found in human (Krzysik-Walker et al., 2008). They require insulin doses greater than four times that required in mammals to achieve hypoglycemia, and hence they are insulin resistant (Akiba et al., 1999; Dupont et al., 2004; Simon et al., 1977). They are also lacking functional brown adipose tissue and glucose transporter GLUT4 (Seki et al., 2003). Interestingly, the majority (>95%) of de novo fatty acid synthesis (lipogenesis) occurs in the liver in chickens (Goodridge and Ball, 1967; Leveille et al., 1975). As a follow up to our previous study where we have shown that visfatin is expressed in chicken liver and is regulated by nutritional status and leptin administration, we undertook this study to determine the effects of IL-6, TNFα, leptin, T3, and orexin A/B on the expression of visfatin gene in chicken hepatocytes (LMH) in culture.
Section snippets
LMH cell culture
LMH cells (Kawaguchi et al., 1987), purchased from American Type Culture Collection (ATCC® CRL-2117, Manassas, VA), were cultured in McCoy 5A medium supplemented with FBS (10%), chicken serum (1%), penicillin-streptomycin (100 μg/mL), and amphotericin B (100 μg/mL) at 37 °C in a 5% CO2/95% O2 humidified incubator. The medium and reagents were purchased from ThermoFisher Scientific (Waltham, MA). At exponential phase of growth (~80%), the complete medium was removed and replaced by a serum-free
Results and discussion
Visfatin is expressed in several peripheral tissues including visceral adipose tissue, muscle, and hepatocytes (Costford et al., 2010; Curat et al., 2006; Garten et al., 2010) and its plasma concentrations correlated strongly with the amount of human visceral fat indicating its potential implication in the development of obesity-associated insulin resistance and diabetes mellitus. Furthermore, a number of cytokines and adipokines have been reported to regulate visfatin, however the bulk of
Author contributions
S.D. designed research; A.F. and E.G. performed experiments and molecular analyses. S.D. provided reagents; S.D. wrote the paper; A.F., E.G. and S.D., reviewed the paper.
Declaration of Competing Interest
The authors declare that they have no conflicts of interest.
Acknowledgments
This work was supported by research grant from the Arkansas Bioscience Institute (ABI) to SD.
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