(The FASEB Journal. 2007;21:855.6)
© 2007 FASEB
LPIN1-, PPAR-, and SREBF-responsive gene networks regulate mammary lipid synthesis during diet-induced milk fat depression
Massimo Bionaz1,
Liliana Piperova2,
Richard Erdman2 and
Juan J Loor1
1 University of Illinois, Urbana-Champaign, 1207 W. Gregory Dr., Urbana, IL, 61801,
2 University of Maryland, 1413A AnSc/AgEn Bld, College Park, MD, 20742
ABSTRACT
Gene networks regulating bovine mammary lipid synthesis are not well-defined. Accordingly, we studied the effects of feeding cows (n = 5/diet) a control or milk fat-depressing diet (MFD; high-grain, oil-supplemented diet) on mammary mRNA expression by qPCR of 48 genes associated with diverse functions in lipid metabolism, transcription regulation, and apoptosis. MFD down-regulated well-studied genes responsible for de novo fatty acid synthesis and esterification (e.g. ACACA, FASN, DGAT1) but also key genes associated with adiposome formation (ADFP), milk fat secretion (BTN1A1), signal transduction and lipid synthesis (AGPAT6), and transcription regulation (SREBF1, SREBF2, PPARGC1A). SCAP and PPARGC1B expression was 6- and 3-fold greater with MFD. SCAP is required for SREBF1 activation in Golgi. LPIN1, crucial in generation/degradation of lipid-signaling molecules, was 9-fold lower with MFD. Up-regulation of NFKBIA (1.6-fold) and TNFRSF12 (2.4-fold) with MFD was indicative of an inflammatory response. Increased FOS (5-fold) with MFD was suggestive of enhanced apoptosis. Gene network analysis revealed a regulatory loop encompassing SREBF1, SREBF2, PPARGC1A, PPARGC1B, and FOS. LPIN1 exerts direct regulation on ACACA, FASN, SCD, and DGAT1, suggesting a novel role for this gene in mammary lipid synthesis. LPIN1-, SREBF-, and PPAR-responsive gene networks play a role in mammary lipid synthesis regulation. Diet-induced milk fat depression encompasses previously unrecognized genomic adaptations.
