The Concentration of Liver-Expressed Antimicrobial Peptide 2 in Human Milk and Infant Plasma Is Positively Associated with Adiposity and Body Weight in the First Year of Life.

BACKGROUND: The liver-expressed antimicrobial peptide 2 (LEAP2) is a recently recognized anorectic and glucose-regulating hormone with an unknown role in lactation. OBJECTIVES: 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. METHODS: 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. RESULTS: 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 f2 = 1.25) and subscapular (P = 0.008, f2 = 0.68) skinfolds at 1 y old. Maternal LEAP2 was positively associated with insulin (P = 0.005, f2 = 0.30) and prepregnancy 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 y old, predominantly in males. No evidence for LEAP2 mRNA expression was found in mammary cells. CONCLUSIONS: 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.

LEAP2 is associated with impulsivity and reward sensitivity depending on the nutritional status and decreases with protein intake in humans.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Leptin receptor expression in blood mononuclear cells of lactating women is associated with infant body weight: Potential role as a molecular biomarker.

BACKGROUND: Molecular biomarkers of maternal leptin resistance associated with infant weight are needed. OBJECTIVES: To evaluate gene expression of leptin receptor (LEPR), suppressor of cytokine signalling 3 (SOCS3) and insulin receptor in peripheral blood mononuclear cells (PBMCs) of lactating women and their relationship with infant body weight and adiposity. METHODS: At day 10 postpartum, maternal gene expression in PBMCs as well as leptin and insulin concentrations in plasma and milk were assessed (n = 68). Infant weight and BMI z-scores, skinfolds and arm circumference were obtained at 10 days and/or at 3 months old. RESULTS: In mothers with pre-pregnancy overweight or obesity (OW/OB), LEPR expression was reduced (p = 0.013) whereas plasma and milk leptin and milk insulin concentrations were elevated. LEPR expression was positively related with infant weight z-score (Beta (95% CI): 0.40 (0.17, 0.63), p = 0.001) but not with leptin concentrations. SOCS3 expression was positively related with infant weight z-score (Beta (95% CI): 0.28 (0.04, 0.51), p = 0.024) and arm circumference (Beta (95% CI): 0.57 (0.32, 0.82), p < 0.001). Relationships remained significant after adjusting for maternal and infant confounders. CONCLUSIONS: LEPR and SOCS3 gene expression in PBMCs are novel maternal molecular biomarkers that reflect leptin resistance and are associated with infant body weight and adiposity.

Prolonged body weight gain, lifestyle changes and health-related quality of life in children during the COVID-19 pandemic lockdown: A follow-up study.

BACKGROUND: Further investigation is needed to define the impact of long-term pandemic lockdown in children. OBJECTIVES: To examine changes in body mass index z-score (zBMI), lifestyle, Health-Related Quality of Life and proportion of overweight or obesity (OW/OB) in 6- to 9-year-old children in Argentina. METHODS: Observational study with baseline measurements prior to lockdown and follow-up after eight months of strict restrictive measures (November 2020, first visit, n = 144) and after ten months of partial reopening (September 2021, second visit, n = 108). Anthropometric changes from baseline to first visit in lockdown group (LG) were compared with a historical control group (HCG, n = 134). Follow-up visits included anthropometric measures, lifestyle questionnaire and Pediatric Quality of Life Inventory. RESULTS: Change in zBMI was higher in LG [median, IQR: 0.46 (-0.00; 0.83)] vs HCG [median, IQR: 0.02 (-0.31; 0.27)]; p < 0.001, particularly in children with pre-existing OW/OB. In LG, zBMI was higher at first and second visit vs baseline (p < 0.001) and in second visit vs first visit for boys (p = 0.037) but not for girls. The proportion of children with OW/OB increased from baseline (43.5%) to first (56.5%) and second visit (58.3%) (p = 0.029). Unlike girls, the proportion of boys with OW/OB increased from baseline to first and second visit (p = 0.045). Change in zBMI was higher in children with less healthy habits (p < 0.001). CONCLUSIONS: Weight gain continued to increase in boys when lockdown measurements were eased, although sedentary behaviors decreased and quality of life improved, indicating that the effects of pandemic lockdown could be difficult to reverse.

Diversidad de dieta y anemia en mujeres post parto que asisten a un hospital público de La Plata, Buenos Aires / Diet diversity and anemia in postpartum women attending a state hospital in La Plata, Buenos Aires

Resumen Introducción: no se cuenta con información a nivel local de la relación entre la diversidad de dieta y la anemia en mujeres postparto, por lo que se propuso analizar dicha relación en un hospital público de La Plata. Materiales y método: se realizó un estudio analítico transversal en mujeres asistidas durante el primer año postparto, en un Observatorio de Salud del Hospital Sor María Ludovica de la ciudad de La Plata, entre agosto de 2018 y septiembre de 2019. Se obtuvieron datos personales y de laboratorio de las historias clínicas. Los alimentos relevados mediante recordatorios de 24 hs fueron categorizados en 10 grupos. Se consideró diversidad de dieta al consumo ≥5 grupos según el instrumento "Mínimo de diversidad dietaria para mujeres". Se definió anemia como hemoglobina <12 g/dL. La asociación entre la anemia y diversidad de dieta se analizó mediante test exacto de Fisher y se comparó la media de hemoglobina utilizando test de Student. Resultados: se incluyeron 137 mujeres postparto, edad 26 (22;31) años, 53,7% argentinas. 12,4% presentó anemia. 63,5% tuvo diversidad de dieta. "Granos y cereales" fue el grupo más consumido (100%), seguido por "Carne, pollo y pescado" (92,7%) y "Otros vegetales" (85,4%). Los menos consumidos fueron "Legumbres" (6,6%) y "Nueces y semillas" (0,7%). No se halló una asociación estadísticamente significativa entre diversidad de dieta y anemia (p=0,18). Tampoco se halló diferencia en las medias de hemoglobina en mujeres con y sin diversidad de dieta (p=0,99). Conclusiones: la diversidad de dieta no se halló asociada a anemia en mujeres postparto que asisten a un hospital público, esto podría relacionarse a la alta frecuencia de consumo de carnes y cereales fortificados.

Abstract Introduction: there is no information at local level on the relationship between diet diversity and postpartum anemia of women, so we intended to analyze this relationship in a state hospital in La Plata. Materials and method: a cross-sectional analytical study was carried out in women assisted during the first year postpartum, in the Health Observatory of Sor María Ludovica Hospital in La Plata city, between August 2018 and September 2019. Personal and laboratory data were obtained from medical records. Foods surveyed by 24-hour reminders were categorized into 10 groups. Dietary diversity was considered to be the consumption ≥5 groups, according to the "Minimum dietary diversity for women" instrument. Anemia was defined as hemoglobin <12 g / dL. The association between anemia and diet diversity was analyzed using Fisher's exact test and mean hemoglobin was compared using Student's test. Results: 137 postpartum women were included, age 26 (22; 31), 53.7% Argentinian. 12.4% presented anemia. 63.5% had diet diversity. "Grains and cereals" was the most consumed group (100%), followed by "Meat, chicken and fish" (92.7%) and "Other vegetables" (85.4%). The least consumed were "Legumes" (6.6%) and "Nuts and seeds" (0.7%). No statistically significant association was found between diet diversity and anemia (p = 0.18). No difference was found in the hemoglobin means in women with and without diet diversity (p = 0.99). Conclusions: diet diversity was not associated with anemia in postpartum women attending a state hospital, this could be related to the high frequency of consumption of meats and fortified cereals.