Objectives Obesity and poor metabolic health are associated with poor lactation outcomes, potentially driven by elevated tumor necrosis factor alpha (TNF-α) from chronic inflammation. TNF-α reduces lipoprotein lipase (LpL) activity, limiting triglyceride (TG) uptake by the mammary gland for milk synthesis. Our objective here is to determine if TNF-α concentrations in serum and milk are higher in mothers with severely low compared to sufficient milk production and if TNF-α is associated with

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... ma TG. Methods Mothers screened for low milk production were categorized into very low (VL; 177 [87,219] mL/d; n = 23) and moderately low/normal (ML; Median [IQR]: 467 [373,655] mL/d; n = 20) milk production. An external control group had sufficient milk production (EC; 783 [717,818] mL/d; n = 18). Mothers provided a spot milk sample at a morning clinic visit, where fasting blood samples were taken for clinical metabolic health measures. TNF-α concentrations were measured in duplicate by high-sensitivity ELISA in serum and aqueous milk. Group differences were assessed by Wilcoxon Rank Sums Tests or Fisher's Exact Chi Square Test (α = 0.05). Correlations were assessed by Spearman rank order. Results Mothers were 31.3 [27.3, 34.1] years old, delivered at gestational age of 39.4 [38.6, 40.3] weeks, and were 43 [35, 56] days postpartum, with no significant differences among groups. Milk TNF-α was detected in 47% of samples (1.3 [0.8, 2.2] pg/mL). The proportion of detectable TNF-α (D-TNF) in milk was higher in VL compared with ML and EC (71%, 32%, 33% respectively; p = 0.02). Compared to undetected (U-TNF), subjects with D-TNF in milk had higher plasma TG (D-TNF: 94 [68,140] mg/dL; U-TNF: 60 [49, 84] mg/dL; p = 0.001). Serum TNF-α was not significantly different by group (VL: 6.3 [5.8, 7.0] pg/mL; ML: 6.1 [5.6, 6.5]; EC: 5.8 [5.3, 6.6]; p = 0.31), but was correlated with plasma TG (ρ = 0.40, p = 0.002). Conclusions In this exploratory cohort, TNF- α levels were higher in milk from mothers with low milk production, and both milk and serum TNF- α was associated with higher plasma TG. This suggests that proximal TNF-α expression is more associated with reduced mammary LpL activity than circulating serum TNF-α, leading to low milk production. Funding Sources NIH and USDA.