Department of Biosciences, COMSATS University Islamabad, Chak Shahzad, Islamabad, Pakistan.
School of Systems Biology and Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia, United States of America.
PLoS One. 2020 Dec 17;15(12):e0243205. doi: 10.1371/journal.pone.0243205. eCollection 2020.
Neuropeptide S (NPS) is a naturally occurring appetite stimulant, associated with anxiety, stress, and excitement regulation. Neuropeptide S serves as a hypothalamic energy regulator that enhances food intake with a reduced level of satiety. NPS activates fat angiogenesis and the proliferation of new adipocytes in obesity. NPS has an established role in energy regulation by many pre-clinical investigations; however we have limited data available to support this notion in humans. We found significant association of Neuropeptide S receptor (NPSR1) Asn107Ile (rs324981, A>T) polymorphism with obese male participants. The current investigation carried out genotype screening of NPSR1 allele to assess the spectrum of the Asn107Ile polymorphism in obese and healthy Pakistani individuals. We revealed a significant (p = 0.04) difference between AA vs TT + AT genotype distribution of NPSR1 (SNP rs324981,) between obese and healthy individuals (p = 0.04). In this genotype analysis of (SNP rs324981) of the NPSR1 gene, T allele was marked as risk allele with higher frequency in the obese (38%) compared to its frequency in the controls (25%). Single Nucleotide Polymorphism (SNP, rs324981) Asn107Ile of NPSR1gene, that switches an amino acid from Asn to Ile, has been found associated with increased susceptibility to obesity in Pakistani individuals. Furthermore, molecular simulation studies predicted a lower binding affinity of NPSR1 Asn107Ile variant to NPS than the wild-type consistent with the genotype studies. These molecular simulation studies predict a possible molecular mechanism of this interaction by defining the key amino acid residues. However, a significantly (p<0.0001) lower concentration of NPS was recorded independent of genotype frequencies in obese subjects compared to healthy controls. We believe that large scale polymorphism data of population for important gene players including NPSR1 will be more useful to understand obesity and its associated risk factors.
神经肽 S（NPS）是一种天然存在的食欲刺激物，与焦虑、压力和兴奋调节有关。神经肽 S 作为下丘脑的能量调节剂，通过降低饱腹感来促进食物摄入。NPS 激活肥胖中的脂肪血管生成和新脂肪细胞的增殖。许多临床前研究已经证实了 NPS 在能量调节中的作用；然而，我们在人类中可用的数据有限，无法支持这一观点。我们发现，神经肽 S 受体（NPSR1）Asn107Ile（rs324981，A>T）多态性与肥胖男性参与者显著相关。本研究进行了 NPSR1 等位基因的基因分型筛查，以评估肥胖和健康巴基斯坦个体中 Asn107Ile 多态性的范围。我们发现，在肥胖和健康个体之间，NPSR1（SNP rs324981）的 AA 与 TT+AT 基因型分布之间存在显著差异（p=0.04）（p=0.04）。在 NPSR1 基因（SNP rs324981）的这种基因型分析中，T 等位基因被标记为风险等位基因，在肥胖个体中的频率（38%）高于其在对照组中的频率（25%）。NPSR1 基因的单核苷酸多态性（SNP，rs324981）Asn107Ile，它将一个氨基酸从 Asn 转换为 Ile，已被发现与巴基斯坦个体肥胖易感性增加有关。此外，分子模拟研究预测，与野生型相比，NPSR1 Asn107Ile 变体与 NPS 的结合亲和力较低，这与基因型研究一致。这些分子模拟研究通过定义关键的氨基酸残基来预测这种相互作用的可能分子机制。然而，与健康对照组相比，肥胖受试者中 NPS 的浓度显著（p<0.0001）降低，而与基因型频率无关。我们相信，包括 NPSR1 在内的重要基因参与者的大规模群体多态性数据将更有助于了解肥胖及其相关危险因素。
