Abstract
Background. The GNPDA2 (glucosamine-6-phosphate deaminase 2) gene is a member of Glucosamine-6-phosphate (GlcN6P) deaminase subfamily, which encoded an allosteric enzyme of GlcN6P. Genome-wide association studies (GWAS) have shown that variations of human GNPDA2 are associated with body mass index and obesity risk, but its function and metabolic implications remain to be elucidated.The object of this study was to characterize the gene structure, expression, and biological functions of GNPDA2 in chickens.Methods. Variant transcripts of chicken GNPDA2 and their expression were investigated using rapid amplification of cDNA ends (RACE) system and real-time quantitative PCR technology. We detected the GNPDA2 expression in hypothalamic, adipose, and liver tissue of Xinghua chickens with fasting and high-glucose-fat diet treatments, and performed association analysis of variations of GNPDA2 with productive traits in chicken. The function of GNPDA2 was further studied by overexpression and small interfering RNA (siRNA) methods in chicken preadipocytes.Results.Four chicken GNPDA2 transcripts (cGNPDA2-a∼cGNPDA2-d) were identified in this study. The complete transcript GNPDA2-a was predominantly expressed in adipose tissue (subcutaneous fat and abdominal fat), hypothalamus, and duodenum. In fasting chickens, the mRNA level of GNPDA2 was decreased by 58.8% (P < 0.05) in hypothalamus, and returned to normal level after refeeding. Chicken fed a high-glucose-fat diet increased GNPDA2 gene expression about 2-fold higher in adipose tissue (P < 0.05) than that in the control (fed a basal diet), but decreased its expression in hypothalamus. Two single-nucleotide polymorphisms of the GNPDA2 gene were significantly associated with body weight and a number of fatness traits in chicken (P < 0.05).Conclusion. Our findings indicated that the GNPDA2 gene has a potential role in the regulation of body weight, fat and energy metabolism in chickens.
Highlights
Obesity is a common nutritional disorder and increase risk of several diseases, such as hypertension, cardiovascular disease and type II diabetes (Kopelman, 2000; Flegal et al, 2007; Finkelstein et al, 2008)
The GNPDA2 gene encodes an allosteric enzyme of Glucosamine-6-phosphate deaminase (GlcN6P), which can catalyzes the reversible conversion of D-glucosamine-6phosphate into D-fructose-6-phosphate and ammonium (Arreola et al, 2003)
The results of UCSC genome BLAST showed that the chicken GNPDA2 was 7,453 bp long, which located at chromosome 4 and spanned from 67202451 to 67209903
Summary
Obesity is a common nutritional disorder and increase risk of several diseases, such as hypertension, cardiovascular disease and type II diabetes (Kopelman, 2000; Flegal et al, 2007; Finkelstein et al, 2008). The variations of GNPDA2 were found to be associated with BMI or risk of obesity in children and old age population (Elks et al, 2010; Mejía-Benítez et al, 2013; Murphy et al, 2013; Xi et al, 2013a; Pillay et al, 2015) It modulated the susceptibility of hypertension and type II diabetes (Takeuchi et al, 2011; Robiou-du-Pont et al, 2013; Xi et al, 2013b; Xi et al, 2014; Kong et al, 2015). Our findings indicated that the GNPDA2 gene has a potential role in the regulation of body weight, fat and energy metabolism in chickens
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