人类餐前血浆肝表达抗菌肽 2（LEAP2）浓度与饥饿感呈负相关，与胃饥饿素无关。
Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.
机构信息
Instituto de Desarrollo e Investigaciones Pediátricas (IDIP), HIAEP Sor María Ludovica de la Plata, Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), Calle 63 # 1069, La Plata, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina.
出版信息
Eur J Nutr. 2024 Apr;63(3):751-762. doi: 10.1007/s00394-023-03304-8. Epub 2023 Dec 29.
PURPOSE
The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations.
METHODS
We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60 min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB).
RESULTS
Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (β: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (β: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (β: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (β: - 11.16; 95% CI: - 18.52, - 3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner.
CONCLUSIONS
LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans.
TRIAL REGISTRATION
The study was retrospectively registered in clinicaltrials.gov (April 2023).
CLINICALTRIALS
gov Identifier: NCT05815641.
目的
肝表达的抗菌肽 2（LEAP2）是一种新发现的肽激素，通过生长激素促分泌素受体（GHSR）发挥作用，减弱了胃饥饿素的作用，并表现出胃饥饿素独立的作用。由于 LEAP2 的影响开始被阐明，我们研究了血浆 LEAP2 浓度是否随进食状态或性别而变化，以及它是否与葡萄糖代谢和食欲感觉有关。
方法
我们进行了一项单餐研究，在 44 名参与者（n=21 名女性）中，评估了早餐前和早餐后 60 分钟的血浆 LEAP2、胃饥饿素、胰岛素和葡萄糖浓度以及饥饿、食欲、预期食物摄入量、饱腹感的视觉模拟量表，这些参与者体重正常（NW）或超重/肥胖（OW/OB）。
结果
OW/OB 个体的餐前血浆 LEAP2 浓度高约 1.6 倍，而胃饥饿素浓度低约 2.0 倍（p<0.001），与性别无关。在调整了体重指数（BMI）和性别后，餐前血浆 LEAP2 浓度与 BMI（β：0.09；95%CI：0.05，0.13；p<0.001）、脂肪量（β：0.05；95%CI：0.01，0.09；p=0.010）和血糖（β：0.24；95%CI：0.05，0.43；p=0.021）呈直接关系，而血浆胃饥饿素浓度与 BMI 和脂肪量呈负相关，但与血糖无关。OW/OB 女性餐后血浆 LEAP2 浓度升高约 58%（p=0.045），但 NW 女性或男性则没有升高。餐前血浆 LEAP2 浓度与饥饿评分呈负相关（β：-11.16；95%CI：-18.52，-3.79；p=0.004），这种关系独立于 BMI、性别和胃饥饿素。
结论
LEAP2 作为一种关键的激素，参与了人类代谢和食欲的调节。
试验注册
该研究在 clinicaltrials.gov 上进行了回顾性注册（2023 年 4 月）。
临床试验
gov 标识符：NCT05815641。
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