Maternal Obesity and Excessive Gestational Weight Gain Influence Endocannabinoid Levels in Human Milk Across Breastfeeding: Potential Implications for Offspring Development

<b>Background/Objectives:</b> Endocannabinoids are endogenous bioactive lipids that promote neurodevelopment and positive energy balance. Increased levels of endocannabinoids are associated with obesity, but the effect of maternal obesity on breast milk endocannabinoids across lactation is mostly unknown. <b>Methods:</b> Women from Rio de Janeiro (Brazil) (n = 92) were followed from the third trimester of pregnancy to 119 days postpartum, and milk samples were analyzed in the postpartum days 2-8 (T1), 28-47 (T2), and 88-119 (T3). We assessed the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) by high-performance liquid chromatography-mass spectrometry, leptin and insulin by immunoassay, and macronutrients by colorimetric assays in milk samples. <b>Results:</b> Milk AEA concentration was higher in T2 compared with T1 or T3, while 2-AG levels were higher in T2 and T3 compared with T1. Milk endocannabinoids were directly correlated with pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and milk triglycerides. Triglyceride and leptin levels were higher in mature milk (T2 and T3) of women with BMI > 25 or excessive GWG. Adjusted linear regression models showed a positive association between excessive GWG and milk 2-AG (β = 1629; 95% CI: 467-2792; <i>p</i> = 0.008). <b>Conclusions:</b> The endocannabinoid levels are higher in mature milk from women with obesity or excessive GWG, which may impact offspring development and metabolism.