de Soysa Ann Kristin Hjelle, Langaas Mette, Grill Valdemar, Martins Catia, Løvold Mostad Ingrid
Outpatient Obesity Clinic, Clinic of Surgery, St. Olavs hospital-Trondheim University Hospital, Trondheim, Norway.
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
PLoS One. 2025 Jan 10;20(1):e0312815. doi: 10.1371/journal.pone.0312815. eCollection 2025.
Associations between variants in the FTO locus and plasma concentrations of appetite related hormones are inconsistent, and might not work in a dose dependent fashion in people with obesity. Moreover, it is relevant to report meal related plasma concentrations of these hormones in persons with obesity given the growing interest in their pharmacological potential in obesity therapy. We find it clinically relevant to examine associations between the SNP rs9939609 genotypes and homeostatic appetite regulation in individuals with BMI ≥35 kg/m2. This study explored associations of the rs9939609 genotypes to plasma concentrations of acylated ghrelin, active glucagon-like peptide 1 (GLP-1), and total peptide YY (PYY), and moderating effects of fat mass (FM), in 96 adults (69% female) with BMI ≥35 kg/m2, using a cross sectional observation study designed to have 1/3 of participants each with genotypes TT, AT and AA, respectively. Participants were median (25th, 75th percentile) 42.5 (32, 50) years of age, weighed 120.9 (109.6, 142.4) kg, and had a BMI of 42.8 (39.5, 46.4) kg/m2. Acylated ghrelin, active GLP-1, and total PYY were measured in the fasted state and half-hourly for 2.5h after a standardized meal. We evaluated associations between genotype and appetite hormones in regression analysis controlling for FM and sex. Genotype did not associate with fasting or postprandial (area under curve, AUC) GLP-1 or PYY. Genotype did not associate with fasting acylated ghrelin, but in females with genotype AA, increased FM was associated with higher fasting and postprandial (AUC) acylated ghrelin concentrations relative to genotypes TT (fasting p = 0.025; AUC p = 0.004) and AT (fasting p = 0.002; AUC p < 0.001). This novel finding warrants further investigation.
FTO基因座变异与食欲相关激素血浆浓度之间的关联并不一致，在肥胖人群中可能不存在剂量依赖性作用。此外，鉴于人们对这些激素在肥胖治疗中的药理潜力越来越感兴趣，报告肥胖人群中与进餐相关的这些激素血浆浓度具有重要意义。我们发现，在体重指数（BMI）≥35kg/m²的个体中，研究单核苷酸多态性（SNP）rs9939609基因型与稳态食欲调节之间的关联具有临床相关性。本研究采用横断面观察性研究，在96名BMI≥35kg/m²的成年人（69%为女性）中，探究rs9939609基因型与酰化胃饥饿素、活性胰高血糖素样肽1（GLP-1）和总肽YY（PYY）血浆浓度之间的关联，以及脂肪量（FM）的调节作用，研究设计使参与者中基因型TT、AT和AA的比例各占1/3。参与者的年龄中位数（第25、75百分位数）为42.5（32，50）岁，体重为120.9（109.6，142.4）kg，BMI为42.8（39.5，46.4）kg/m²。在空腹状态下以及标准化餐后2.5小时内每半小时测量一次酰化胃饥饿素、活性GLP-1和总PYY。在控制FM和性别的回归分析中，我们评估了基因型与食欲激素之间的关联。基因型与空腹或餐后（曲线下面积，AUC）GLP-1或PYY均无关联。基因型与空腹酰化胃饥饿素无关联，但在基因型为AA的女性中，相对于基因型TT（空腹p = 0.025；AUC p = 0.004）和AT（空腹p = 0.002；AUC p < 0.001），FM增加与空腹和餐后（AUC）酰化胃饥饿素浓度升高有关。这一新颖的发现值得进一步研究。
