Brown Fat-Activating Lipokine 12,13-diHOME in Human Milk Is Associated with Infant Adiposity

Context: Little is known about the specific breastmilk components responsible for protective effects on infant obesity. Whether 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), an oxidized linoleic acid metabolite and activator of brown fat metabolism, is present in human milk, or linked to infant adiposity, is unknown. Objective: To examine associations between concentrations of 12,13-diHOME in human milk and infant adiposity. Design: Prospective cohort study from 2015 to 2019, following participants from birth to 6 months of age. Setting: Academic medical centers. Participants: Volunteer sample of 58 exclusively breastfeeding mother-infant pairs; exclusion criteria included smoking, gestational diabetes, and health conditions with the potential to influence maternal or infant weight gain. Main Outcome Measures: Infant anthropometric measures including weight, length, body mass index (BMI), and body composition at birth and at 1, 3, and 6 months postpartum. Results: We report for the first time that 12,13-diHOME is present in human milk. Higher milk 12,13-diHOME level was associated with increased weight-for-length Z-score at birth (β = 0.5742, P = 0.0008), lower infant fat mass at 1 month (P = 0.021), and reduced gain in BMI Z-score from 0 to 6 months (β = -0.3997, P = 0.025). We observed similar associations between infant adiposity and milk abundance of related oxidized linoleic acid metabolites 12,13-Epoxy-9(Z)-octadecenoic acid (12,13-epOME) and 9,10-Dihydroxy-12-octadecenoic acid (9,10-diHOME), and metabolites linked to thermogenesis including succinate and lyso-phosphatidylglycerol 18:0. Milk abundance of 12,13-diHOME was not associated with maternal BMI, but was positively associated with maternal height, milk glucose concentration, and was significantly increased after a bout of moderate exercise. Conclusions: We report novel associations between milk abundance of 12,13-diHOME and adiposity during infancy.