Human Mammary Epithelial Cell Gene Expression and Product Secretion of Milk Lipids during Secretory Activation

Abstract

BackgroundThe gene expression of lipid biosynthetic enzymes during initiation of lactation in humans in unknown.ObjectiveTo study mRNA expression of lipid metabolic enzymes in human mammary epithelial cell (MEC) in conjunction with the measurement of milk fatty acid (FA) composition during secretory activation.SubjectsGene expression from mRNA isolated from milk fat globule (MFG), a reflection of gene expression in MEC, and milk FA composition were measured from 6h to 42d postpartum in 7 normal women.ResultsOver the first 96h postpartum, gene expression of all aspects of lipid metabolism and milk FA production increased several folds, including: lipolysis at the MEC membrane, FA uptake from blood, intracellular FA transport, de novo FA synthesis, FA and glycerol activation, FA elongation, FA desaturation, synthesis of triglycerides, cholesterol synthesis and lipid droplet formation. Gene expression of the key lipid synthesis regulator, sterol regulatory element‐binding transcription factor1 (SREBF1), increased 2.0‐fold by 36h and remained elevated over the study duration. The mRNA expression of thyroid hormone responsive (THRSP) and insulin‐induced2 (INSIG2) genes increased progressively to plateau by 96h. In contrast, mRNA expression of peroxisome proliferator‐activated receptor gamma (PPARG) decreased several folds. With the onset of lactation, de novo synthesis of FAs (C6‐C12) was the most prominent change in milk FA composition and mirrored the expression of FA synthesis genes.ConclusionMilk fat synthesis and secretion in humans is a complex process requiring the orchestration of a wide variety of pathways of which SREBF1 may play a primary role.Grant Funding Source: USDA/ARS Grant # 6250–51000