Instituto de Desarrollo e Investigaciones Pediátricas (IDIP), Children's Hospital HIAEP "Sor María Ludovica" La Plata-Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), La Plata, Argentina.
CONICET La Plata, La Plata, Argentina.
Diabetes Obes Metab. 2024 Oct;26(10):4734-4743. doi: 10.1111/dom.15850. Epub 2024 Aug 14.
Liver-expressed antimicrobial peptide 2 (LEAP2) dynamics in human plasma and its association with feeding behaviour remain poorly understood. Therefore, this study aims: (a) to investigate fasting LEAP2 in participants with normal weight or with overweight or mild obesity (OW/OB); (b) to study the association between fasting LEAP2 and anthropometric and metabolic traits, feeding behaviour, LEAP2 genetic variants and blood cell DNA methylation status; and (c) to ascertain postprandial changes in LEAP2 after high protein intake and the association with feeding behaviour and food intake.
Anthropometric and behavioural measures, genotyping, methylation profiling, plasma glucose and LEAP2 concentrations were assessed in 327 females and males. A subgroup of 123 participants received an ad libitum high-protein meal, and postprandial LEAP2 concentration and behavioural measures were assessed.
LEAP2 concentration was higher in participants with OW/OB (p < 0.001) and in females (p < 0.001), and was associated with LEAP2 single nucleotide polymorphisms rs765760 (p = 0.012) and rs803223 (p = 0.019), but not with LEAP2 methylation status. LEAP2 concentration was directly related to glycaemia (p = 0.001) and fullness (p = 0.003) in participants with normal weight, whereas it was associated with body mass index (p = 0.018), waist circumference (p = 0.014) and motor impulsivity in participants with OW/OB (p = 0.005). A negative association with reward responsiveness was observed in participants with OW/OB (p = 0.023). LEAP2 concentration was inversely associated with food intake (p = 0.034) and decreased after a high-protein meal (p < 0.001), particularly in women (p = 0.002).
Increased LEAP2 in participants with OW/OB is associated with behavioural characteristics of obesity. Our results show sexual dimorphism in LEAP2 concentration before and after food intake and highlight the role of LEAP2 in feeding regulation.
人血浆中肝表达抗菌肽 2（LEAP2）的动态及其与进食行为的关系仍知之甚少。因此，本研究旨在：（a）研究正常体重或超重或轻度肥胖（OW/OB）参与者的空腹 LEAP2；（b）研究空腹 LEAP2 与人体测量和代谢特征、进食行为、LEAP2 遗传变异和血细胞 DNA 甲基化状态之间的关系；（c）确定高蛋白摄入后 LEAP2 的餐后变化及其与进食行为和食物摄入的关系。
对 327 名女性和男性进行了人体测量和行为测量、基因分型、甲基化谱分析、血浆葡萄糖和 LEAP2 浓度评估。123 名参与者的亚组接受了随意的高蛋白膳食，评估了餐后 LEAP2 浓度和行为测量。
OW/OB 参与者（p<0.001）和女性（p<0.001）的 LEAP2 浓度较高，与 LEAP2 单核苷酸多态性 rs765760（p=0.012）和 rs803223（p=0.019）相关，但与 LEAP2 甲基化状态无关。在体重正常的参与者中，LEAP2 浓度与血糖（p=0.001）和饱腹感（p=0.003）直接相关，而在 OW/OB 参与者中，LEAP2 浓度与体重指数（p=0.018）、腰围（p=0.014）和运动冲动性（p=0.005）相关。在 OW/OB 参与者中，与奖励反应性呈负相关（p=0.023）。LEAP2 浓度与食物摄入量呈负相关（p=0.034），高蛋白餐后降低（p<0.001），特别是女性（p=0.002）。
OW/OB 参与者 LEAP2 的增加与肥胖的行为特征有关。我们的研究结果表明，LEAP2 浓度在进食前后存在性别二态性，并强调了 LEAP2 在进食调节中的作用。
