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LPIN1‐, PPAR‐, and SREBF‐responsive gene networks regulate mammary lipid synthesis during diet‐induced milk fat depression
Author(s) -
Bionaz Massimo,
Piperova Liliana,
Erdman Richard,
Loor Juan J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1106-d
Subject(s) - lipid metabolism , biology , sterol regulatory element binding protein , ppargc1a , gene expression , peroxisome proliferator activated receptor , fatty acid synthase , signal transduction , lipid droplet , endocrinology , microbiology and biotechnology , transcription factor , gene , medicine , biochemistry , coactivator
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.