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; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina.
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.
J Nutr. 2024 Nov;154(11):3388-3399. doi: 10.1016/j.tjnut.2024.09.008. Epub 2024 Sep 12.
The liver-expressed antimicrobial peptide 2 (LEAP2) is a recently recognized anorectic and glucose-regulating hormone with an unknown role in lactation.
The objectives of this study were as follows: 1) to assess LEAP2 presence in human milk and putative associations with infant body weight and adiposity in the first year of life, 2) to evaluate the impact of maternal weight status on LEAP2 concentration, and 3) to explore the relationship between infant plasma LEAP2 concentration and body weight and adiposity.
This prospective cohort observational study assessed LEAP2 concentration in plasma and milk from lactating women with normal weight (n = 26) or overweight or obesity (OW/OB, n = 26) at 6 mo postpartum and in 6-mo-old infant plasma, examining associations with metabolic and anthropometric variables at 6 mo and 1 y. Maternal plasma and milk leptin and insulin concentrations were also measured. LEAP2 expression in milk fat globules and single-cell-RNA-sequencing datasets was evaluated.
LEAP2 was detected in all milk samples assessed (2.08 ± 0.65 ng/mL) and was positively associated with infant triceps (P = 0.022, Cohen f = 1.25) and subscapular (P = 0.008, f = 0.68) skinfolds at 1 y old. Maternal LEAP2 was positively associated with insulin (P = 0.005, f = 0.30) and prepregnancy body mass index (BMI) (P = 0.040, f = 0.17) and negatively associated with gestational weight gain (P = 0.008, f = 0.25) and postpartum weight retention (P = 0.036, f = 0.15). Maternal LEAP2 was higher in plasma (P = 0.039), but not milk of lactating women with OW/OB. Infant plasma LEAP2 (1.98 ± 0.28 ng/mL) was positively associated with weight (P = 0.004, f = 0.63), BMI (P = 0.049, f = 0.37), and weight-for-length (P = 0.024, f = 0.35) z-scores at 1 y old, predominantly in males. No evidence for LEAP2 mRNA expression was found in mammary cells.
Milk LEAP2 is a bioactive component that plays a role in infant fat accretion in the first year of life. Although maternal LEAP2 responds to weight change in pregnancy and lactation, infant plasma LEAP2 might be involved in body weight regulation in early life. This trial was registered at clinicaltrials.gov as NCT05798676.
肝表达的抗菌肽 2（LEAP2）是一种最近被发现的具有厌食和调节血糖作用的激素，但其在哺乳期的作用尚不清楚。
本研究旨在：1）评估 LEAP2 在人乳中的存在情况，以及其与婴儿生命第一年体重和肥胖的潜在相关性；2）评估产妇体重状况对 LEAP2 浓度的影响；3）探讨婴儿血浆 LEAP2 浓度与体重和肥胖的关系。
本前瞻性队列观察性研究评估了产后 6 个月体重正常（n=26）或超重或肥胖（OW/OB，n=26）的哺乳期妇女血浆和母乳中的 LEAP2 浓度，并在 6 个月和 1 岁时检测与代谢和人体测量学变量的相关性。还测量了产妇血浆和母乳中的瘦素和胰岛素浓度。评估了乳脂肪球和单细胞 RNA 测序数据集的 LEAP2 表达。
所有评估的母乳样本均检测到 LEAP2（2.08±0.65ng/mL），并与 1 岁时婴儿三头肌（P=0.022，Cohen f=1.25）和肩胛下皮褶（P=0.008，f=0.68）呈正相关。产妇 LEAP2 与胰岛素（P=0.005，f=0.30）和孕前体重指数（BMI）（P=0.040，f=0.17）呈正相关，与妊娠体重增加（P=0.008，f=0.25）和产后体重滞留（P=0.036，f=0.15）呈负相关。OW/OB 产妇血浆中 LEAP2 浓度高于母乳（P=0.039）。婴儿血浆 LEAP2（1.98±0.28ng/mL）与 1 岁时的体重（P=0.004，f=0.63）、BMI（P=0.049，f=0.37）和体重-身长比（P=0.024，f=0.35）呈正相关，主要见于男性。在乳腺细胞中未发现 LEAP2 mRNA 表达的证据。
母乳 LEAP2 是一种具有生物活性的成分，在婴儿生命的第一年中发挥着促进脂肪堆积的作用。虽然产妇 LEAP2 对妊娠和哺乳期的体重变化有反应，但婴儿血浆 LEAP2 可能参与了生命早期的体重调节。本试验在 clinicaltrials.gov 上注册为 NCT05798676。
