The concentration of LEAP2 in human milk and infant plasma is positively associated with adiposity and body weight in the first year of life

Abstract

BackgroundThe liver-expressed antimicrobial peptide 2 (LEAP2) is a recently recognized anorectic and glucose-regulating hormone, with unknown role in lactation. Objectives1) Assess LEAP2 presence in human milk and putative associations with infant body weight and adiposity in the first year of life, 2) Evaluate the impact of maternal weight status on LEAP2 concentration and 3) Explore the relationship between infant plasma LEAP2 concentration and body weight and adiposity. MethodsThis prospective cohort observational study assessed LEAP2 concentration in plasma and milk from lactating women with normal weight (n=26) or overweight/obesity (OW/OB, n=26) at six months postpartum and in 6-month-old infant plasma, examining associations with metabolic and anthropometric variables at 6 months and 1 year. 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. ResultsLEAP2 was detected in all milk samples assessed (2.08±0.65 ng/ml) and was positively associated with infant triceps (p=0.022, Cohen f2=1.25) and subscapular (p=0.008, f2=0.68) skinfolds at 1 year old. Maternal LEAP2 was positively associated with insulin (p=0.005, f2=0.30) and pre-pregnancy body mass index (BMI) (p=0.040, f2=0.17) and negatively associated with gestational weight gain (p=0.008, f2=0.25) and postpartum weight retention (p=0.036, f2=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, f2=0.63), BMI (p=0.049, f2=0.37), and weight-for-length (p=0.024, f2=0.35) z-scores at 1 year old, predominantly in males. No evidence of LEAP2 mRNA expression was found in mammary cells. ConclusionsMilk LEAP2 is a bioactive component that plays a role in infant fat accretion in the first year of life. While maternal LEAP2 responds to weight change in pregnancy and lactation, infant plasma LEAP2 might be involved in body weight regulation in early life. Clinical Trial RegistryThis study was registered at clinicaltrials.gov as NCT05798676. https://clinicaltrials.gov/study/NCT05798676