Elongation and Desaturation Pathways in Mammary Gland Epithelial Cells Are Associated with Modulation of Fat and Membrane Composition

Abstract

The aim was to determine the relative role of each of the lactogenic hormones (insulin, prolactin and hydrocortisol) and their combinations in regulating elongation and desaturation of polyunsaturated fatty acids and subsequently on composition of cellular lipid compartments in mammary epithelia. Cultured cells of the mammary gland epithelial cell line HC11 were subjected to 48 h of hormonal treatment with different combinations of insulin, hydrocortisone and prolactin. Only the combination of all three hormones induced differentiation according to the marker β-casein gene expression. Inclusion of insulin in the treatment medium increased total fatty acid amount by 50% and increased the concentration of monounsaturated fatty acids by 12% while decreasing that of saturated fatty acids by 35%. Changes in the levels of fatty acids by chain length and saturation paralleled mRNA expression of the desaturases and elongases, whose expression levels were regulated again by inclusion of all three hormones in the treatment medium. Gene expression levels of the Δ6 desaturase and elongase 5 genes (Elovl 5) increased by approximately 1.5-fold, whereas expression of Elovl 4 decreased in the presence of all three hormones. Insulin was the main hormone inducing compositional differences in membrane lipids, increasing phosphatidylethanolamine and phosphatidylinositol and decreasing sphingomyelin and cholesterol. The results indicate that mammary gland epithelial cells express five out of the seven known elongase subtypes which are regulated primarily by the processes of differentiation and produce major compositional changes in mammary gland epithelial cells.

Fatty acid and phospholipid biosynthetic pathways are regulated throughout mammary epithelial cell differentiation and correlate to breast cancer survival

“…Probability of relapse-free survival in all breast cancers, HR, and log-rank test were calculated for analysis of significance. insulin, cortisol, and prolactin induced Fads2 and Elovl6 expression that was consistent with C16:0 reduction and C16:1 increase compared with results for incubation with each hormone separately (47). Our results are in agreement with these studies and provide further evidence of consistency in reproducing functional differentiation of HC11 cells in vitro.…”

“…The HC11 cell line has long been used to study lactogenic hormone effects on gene and protein expression in MECs. Regarding lipid metabolism, it was only recently shown that a combination of the lactogenic hormones insulin, cortisol, and prolactin induced Fads2 and Elovl6 expression that was consistent with C16:0 reduction and C16:1 increase compared with results for incubation with each hormone separately (47). Our results are in agreement with these studies and provide further evidence of consistency in reproducing functional differentiation of HC11 cells in vitro .…”

Bovine Mammary Nutrigenomics and Changes in the Milk Composition due to Rapeseed or Sunflower Oil Supplementation of High-Forage or High-Concentrate Diets

“…It has been reported in studies in humans, that the intake of fats such as SO modifies the effects of the polymorphism of the ELOVL6 gene, suggesting a relationship between these two factors [37]. Recently, the expression of ELOVL6 in murine mammary epithelial cells has been demonstrated in vitro [38]. However, determining its roles in ruminant mammary lipid metabolism and in the milk FA composition will require further investigations.…”

Effect of different exogenous fatty acids on the cytosolic triacylglycerol content in bovine mammary cells

“…Fatty acids are components of cell membranes, and FA provided in the media of cultured mammary epithelial cells are primarily incorporated into cell membrane phospholipids ( Mida et al., 2012 ). The relative amounts of SFA and UFA, as well as chain length of FA that constitute membranes, are important factors that determine membrane fluidity.…”