Upregulation of mammary gland OCTNs maintains carnitine homeostasis in suckling infants

► l-Carnitine transport from maternal stores into breast milk is critical for fatty acid oxidation and ketogenesis for newborn cerebral metabolism. ► No studies have shown dynamic regulation of carnitine/organic cation transporters Octn1, -2 and -3 at different mammary gland developmental stages. ► We show unique expression patterns of Octn1, -2 and -3 in murine mammary gland in virginal, gestational, post-partum and post-lactating stages. ► We demonstrate dynamic upregulation of all three Octns in gestational and lactating mammary gland and downregulation post-lactation. ► Octn3 was primarily localized to myoepithelial cells suggesting a role in milk let down. Background: Transport of l-carnitine, essential cofactor of fatty acid metabolism, into breast milk is critical for the normal growth and development of the suckling infant. Objective: To increase understanding of developmental expression of carnitine/organic cation (Octn) transporter family at different stages of murine breast development for carnitine delivery. Methods: We applied our transporter-specific antibodies to mOctn1, mOctn2 and mOctn3 to sections of mammary glands of virginal non-lactating, pregnant, late lactating and post-lactating C3H females. Results: We demonstrated differential expression of mOctn1, -2 and -3 in epithelial ducts, specialized myoepithelial cells and fatty stroma. There was notable upregulation of all three Octns and mRNA by RT-PCR concurrent with an increase in epithelial ducts in breasts of pregnant (15 days gestation) and lactating mice (15-days post-partum) compared to virginal 6 week old females, and notable downregulation in expression of Octns 15 days after cessation of lactation. In lactating murine mammary gland at 15 days post-partum, there was a marked increase of fat globules in epithelial ducts. Octn1 and Octn2 had similar expression patterns in lactating gland cells which formed fat globules that were exocytosed into the lumen of alveoli along with transporters Octn1 and Octn2. Octn3 was primarily localized to myoepithelial cells surrounding the ducts at all stages of breast development. Conclusions: There is a dynamic upregulation of the Octn family in pregnant and lactating breasts which likely provides the suckling infant with adequate carnitine for the rapid postnatal upregulation of fatty acid oxidation and ketogenesis critical for cerebral energy metabolism during fasting hypoglycemia.