Gene networks regulating lipid synthesis in bovine mammary gland during the lactation cycle

Abstract

Regulation of lipid synthesis in the bovine mammary gland is a complex dynamic process likely controlled by interacting gene networks. Little is known about these sensing and signal transduction circuits. Mammary biopsies from 6 Holstein cows were obtained at -15, 1, 15, 30, 60, 120, and 240 days relative to parturition (DIM), and RNA used for qPCR of ABCA1, ABCG2, ACACA, ADFP, BTN1A1, CD36, DGAT1, ESR1, FABP3, FADS1, FASN, GPAM, INSIG1, INSIG2, LPIN1, LPL, PPARG, PPARGC1A, PPARGC1B, RETN, SCAP, SCD, SREBF1, SREBF2, and THRSP. These genes are relatively well-studied in non-ruminant cells and tissues due to their key roles in aspects of carbohydrate and lipid metabolism. Except for PPARGC1B, lactation increased (P < 0.01) mRNA expression of other genes by 1.5 (ABCA1) to 80-fold (FABP3, LPL) relative to day -15. Peak expression patterns were observed at 60 DIM for all genes except PPARG, PPARGC1A, SCAP, and THRSP, which peaked (3-, 10-, 1.7-, and 3-fold, respectively) at 120 DIM. Network analysis using Ingenuity Pathway Analysis revealed regulatory loops consisting of SREBF2, SREBF1, PPARG, PPARGC1A, and PPARGC1B along with their down-stream targets (e.g. SCD, ACACA, INSIG1, FABP3). LPIN1, INSIG2, and SCAP appeared to independently regulate expression of several lipogenic genes. LPIN1 (25-fold higher on day 60) and AGPAT6 (16-fold higher on day 60) seem to play a role in bovine milk fat synthesis regulation. Results suggest that mammary lipid synthesis is regulated by complex gene networks including transcription factors and novel genes.