Thursday, May 22, 2025
5/22/2025
Maternal exercise during lactation to ignite infant metabolism - PROJECT SUMMARY/ABSTRACT Breastfeeding reduces risk of childhood obesity and diabetes, but the mechanisms remain unclear. We recently identified that 12,13-diHOME, a signaling lipid crucial for activating brown adipocyte thermogenesis, is present in human milk. We reported that higher concentration of 12,13-diHOME in milk at 1-mo postpartum was associated with lower infant fat mass. Furthermore, milk levels of 12,13-diHOME, and other metabolites involved in adipocyte thermogenesis, were significantly increased after maternal exercise. Thus, we hypothesize that maternal exercise during lactation protects against childhood obesity by upregulating thermogenic metabolites and lipids in milk. We propose to systematically compare the acute versus chronic effects of maternal exercise on human milk composition, and to test how maternal exercise-induced changes in milk influence metabolic activity and body composition in infants. In Aim 1, we will measure changes in thermogenic metabolites and lipids in human milk in response to a single exercise session and to an 8-week physical activity intervention. We will randomize 100 exclusively breastfeeding mother-infant pairs to either an “Active” group (targeting >8,000 steps/day) or a Control” group (standard of care), with daily activity monitoring from 1 to 3 months postpartum. All participants will complete a supervised acute exercise bout at 1 and 3 months postpartum. Milk samples collected before and after exercise will be used for metabolomic and lipidomic analyses. In Aim 1A, we will determine how milk composition is affected by the activity intervention by comparing the “Active” vs. “Control” groups. The goal of Aim 1B is to measure acute changes in milk composition in response to a single exercise bout. We will also determine whether the 8-week activity program alters milk composition responses to the single exercise session. In Aim 2, we will test whether chronic and acute maternal exercise alterations of milk-derived mammary epithelial cells (MECs) mediate adaptive changes in human milk composition. Building on our preliminary data showing that mRNA signatures in MECs are altered by maternal obesity and exercise, we will analyze mRNA signatures and protein content for key enzymes and signal transduction pathways for lipid and nucleotide sugar metabolites, using samples from the acute and chronic activity experiments. In Aim 3, we will link maternal exercise-induced changes in human milk to metabolism and body composition in infants of participants recruited in Aim 1. The goal of Aim 3A is to define the immediate metabolic impact on infants fed with “after-exercise milk” relative to a feeding with “before-exercise milk”. This will involve measuring thermogenic activation via infrared thermography, energy expenditure with indirect calorimetry, and analyzing the infant plasma metabolome and lipidome at 1 and 3 months. In Aim 3B, we will compare adiposity in infants of mothers in the Active vs. Control groups in the first year of life; outcomes will include body composition (Pea Pod and DXA), beige/brown fat anatomy (MRI), and infant growth (z-BMI). These studies will provide key data to guide a larger clinical trial of exercise during lactation.
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