Influence of variants in the NPY gene on obesity and metabolic syndrome features in Spanish children
Introduction
Neuropeptide Y (NPY) is a peptide that acts as a neurotransmitter or neuromodulator. It has been implicated in several human diseases including obesity, alcoholism, schizophrenia, and depression, each of which might be considered to have behavioral or psychiatric components [3]. The role of NPY in the hypothalamic control of energy balance is well established. When this potent orexigenic neuropeptide is chronically administered to the central nervous system, it leads to an increase in food intake, body weight, and adiposity in rats [25], [29]. The obesity induced by NPY is due not only to hyperphagia but also to increased accumulation of lipids in white adipose tissue, inhibition of thermogenesis in brown adipose tissue, stimulation of hyperinsulinemia, and hypersecretion of corticosteroids [1], [21]. Although there is extensive evidence of the key role of NPY in energy regulation in rats, evidence in humans is limited.
The first studies showing a positive association of an NPY gene variant (-880I/D) with obesity were those performed by Bray et al. [2] in Mexican-American families. Additionally, there have been many studies examining the functional Leu7Pro polymorphism (rs16139). This SNP has been associated with a large number of conditions related to obesity and metabolic syndrome traits, including increased body mass index (BMI) in adults [6], development of obesity in young adults [28], risk of hypertension [11], high plasma low-density lipoprotein-cholesterol (LDL-c) in children and adults [9], [22], and elevated plasma triacylglycerols (TAG) [10]. This variant has been associated with metabolic syndrome in patients with coronary artery disease [15]. This SNP has also been shown to correlate with high birth body weight in preschoolers [10], the risk of an accelerated atherosclerotic process or carotid atherosclerosis in adults [11], [17], and the risk of type 2 diabetes mellitus in adults [18], [26].
Other studies of SNPs in the NPY gene have reported an association of rs16147 and rs16135 with ischemic stroke [12], [13], [31] and the onset of atherosclerosis [23]. Additionally, rs16147 has been associated with being overweight [8] and dietary fat intake and changes in blood pressure (BP) [32]. However, there are only two studies that have investigated the association of rs16147 with obesity; one study found no association of this variant with obesity in two different cohorts of adults [30], and the other demonstrated a significant effect of this variation on age-dependent body weight and BMI during childhood and adolescence in a German population [7]. No associations so far have been reported for rs16131. Thus, the objective of the present study was to evaluate whether some variants in the NPY gene, including rs16131, rs16139, and rs16147, are associated with obesity, metabolic syndrome features, and inflammatory and cardiovascular disease (CVD) risk biomarkers in a cohort of Spanish children.
Section snippets
Study design
This is a case–control multicenter study in children. We recruited 292 (149 male and 143 female) obese children and 242 (135 male and 107 female) normal-BMI children, all of them of European-Caucasian heritage and aged 5–15 years between May 2007 and May 2010 in two cities in Spain (Cordoba and Santiago de Compostela). Childhood obesity was defined according to the International Obesity Task Force (IOTF) reference for children [5]. The inclusion criteria were European-Caucasian heritage and the
Children characteristics
Table 1 shows the characteristics of the obese and normal-BMI subjects. The anthropometric measurements (height, weight, BMI, BMI z-score, and waist circumference) as well as most of the clinical and metabolic markers (systolic and diastolic BP, insulin, HOMA-IR, and TAG) were significantly higher in the obese group than in the normal-BMI children. In contrast, total cholesterol and HDL-c levels were lower in the obese subjects, and glucose and LDL-c levels did not differ between the groups.
Discussion
In the present study, we validate the association between the NPY rs16147 genotype and BMI in Spanish children, observing higher BMI values in TT homozygotes as compared with heterozygous C allele carriers. Moreover, we find for the first time a significant association of the intronic rs16131 SNP with higher BMI, insulin, HOMA-IR, TAG, and leptin and lower HDL-c.
The rs16147 variant, located in the promoter region of the gene, is shown in our study to be associated with obesity and lower levels
Conclusion
We confirm the association of rs16147 with obesity in a cohort of Spanish children. Our results suggest that the rs16131 risk allele influences the early onset of obesity and metabolic syndrome features, particularly the elevation of plasma TAG. The question of how these polymorphisms actively play a role in obesity and metabolic syndrome remains unanswered.
Competing interests
The authors declare that they have no competing interests.
Acknowledgements
This work was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Fondo de Investigación Sanitaria [PI 020826, PI051968], the Conserjería de Innovación y Ciencia, Junta de Andalucía [P06-CTS 2203] and the Ministerio de Universidades y Tecnología, Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias, Redes temáticas de investigación cooperativa RETIC [Red SAMID RD08/0072/0028].
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2021, PeptidesCitation Excerpt :Rs16139 heterozygotes had lower MPO (by –0.17 per kg; –0.34, 0.02; p = 0.026) compared to GG-homozygotes, at 25 years of age (Supplementary Table 4). Studies describing the association between NPY genetic variants and weight gain or obesity have been inconclusive, some showing an association [27,29,30,39] while others demonstrating no effect [28,31]. However, studies analysing the association between variants of the NPY and obesity have differed regarding the age of the population under investigation, so this should be considered as a possible reason for variation.
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2019, Diabetes Research and Clinical PracticeCitation Excerpt :The present study show no association between the rs16147 variant and adiposity parameters or weight loss secondary to either of the two diets. A previous meta-analysis [31] reported that the minor alleles of this genetic variant were associated with increased risk of obesity in 942 children. In a previous study using a pediatric cohort [32], a longitudinal relationship between rs16147 and BMI during childhood was also demonstrated.
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2017, Comptes Rendus - BiologiesCitation Excerpt :Agonists: it includes adrenocorticotropic hormone (ACTH), cocaine, amphetamine and α-, β-, and γ-MSH produced by cleavage and post-translational processing of POMC polypeptide [40]. Antagonists: it includes agouti, AgRP [28–30] and NPY [26,27]; MCRs: they belong to the rhodopsin-like family, which is the largest and most intensively studied G-protein coupled receptor (GPCR) family [42].