SREBP1 and Thyroid Hormone Responsive Spot 14 (S14) Are Involved in the Regulation of Bovine Mammary Lipid Synthesis during Diet-Induced Milk Fat Depression and Treatment with CLA

Abstract

Milk fat synthesis in dairy cows can be inhibited by unique fatty acid intermediates that are produced during rumen biohydrogenation. One of these inhibitory intermediates is trans-10, cis-12 conjugated linoleic acid (CLA), and this milk fat depression (MFD) involves a coordinated decrease in mammary expression of lipogenic enzymes. We investigated the sterol response element binding protein (SREBP) transcription factor system in the mammary tissue of cows during MFD, which was induced by a low forage, high oil (LF/HO) diet and trans-10, cis-12 CLA infusion. The LF/HO diet and CLA treatment decreased milk fat yield by 38 and 24%, respectively. Treatments causing MFD decreased expression of SREBP1 and the insulin responsive gene (INSIG) 1, consistent with decreased abundance of active SREBP1. The LF/HO diet also decreased expression of INSIG2 and SREBP cleavage activating protein. In addition, we identified the involvement of thyroid hormone responsive spot 14 (S14) in the regulation of mammary synthesis of milk fat. A broader role for S14 in the trans-10, cis-12 CLA-mediated decrease in fat synthesis was explored by mining publicly available microarray datasets, and we found that mouse adipose expression of S14 was decreased in response to CLA treatment. Overall, the decreased mammary expression of SREBP1, SREBP activation protein, and the coordinated reduction in SREBP1-responsive lipogenic enzymes provides strong support for a central role of SREBP1 in the regulation of milk fat synthesis. In addition, our results provide evidence for an involvement of S14 in mammary regulation of milk fat synthesis and a possible broader role for S14 in the reported antiobesity effects of CLA.

Transcriptional regulation of acetyl-CoA carboxylase α isoforms in dairy ewes during conjugated linoleic acid induced milk fat depression

“…Interestingly, SREBP1, that it is considered a global regulator of lipid synthesis (Eberlé et al, 2004), had a similar response to the ACC-α PIII transcripts in the mammary gland, whereas in adipose tissue had a similar response to ACC-α PI transcripts and FASN. SREBP1 regulates enzymes which synthesize FA and cholesterol from precursor molecules (Horton et al, 2003;Goldstein et al, 2006) and SREBP1 is a major regulator of mammary de novo FA synthesis and the response to dietary factors that modify milk fat in mouse (Anderson et al, 2007) and cow (Harvatine and Bauman, 2006).…”

“…In addition, Barber et al (2005) showed the existence of a fourth promoter expressed predominantly in the brain of ruminants showing the complexity of the regulation of ACC-α. The mechanisms controlling ACC-α expression in different tissues and stages of lactation is not well understood, but a role for the sterol regulatory element-binding protein (SREBP1) family of transcription factors was proposed based on their function as global regulators of expression for many genes involved in lipid synthesis (Harvatine and Bauman, 2006). The scenario becomes even more obscure during altered physiological conditions such as MFD caused by bioactive isomers of CLA (i.e.…”

Effects of fish oil and additional starch on tissue fatty acid profile and lipogenic gene mRNA abundance in lactating goats fed a diet containing sunflower-seed oil

“…A recent study on bovine mammary epithelial cells (McFadden and Corl, 2010) has proposed that the mRNA abundance of SREBF1 (which regulates the transcription of lipogenic genes in ruminants; Harvatine and Bauman, 2006) could be controlled by LXRA, a transcription factor whose mRNA was present at low levels in the mammary tissue of lactating goats (Figure 2). A relevant role of PPARG in the lactating mammary gland has also been suggested in cows (Bionaz and Loor, 2008b;Kadegowda et al, 2009), but its mRNA abundance in the mammary tissue of goats was very low compared with that in ATs (Figure 2).…”

“…Molecular biology techniques offer a valuable and new approach to study the mechanisms underlying the nutritional regulation of mammary lipogenesis. In this regard, reductions in milk fat synthesis in cows fed plant oils rich in n-6 PUFA and fish oil have been related to variations in lipogenic gene expression not only in the mammary gland but also in other body tissues (Harvatine and Bauman, 2006;Thering et al, 2009;Invernizzi et al, 2010). Although these changes were attributed in cows to modifications in the partitioning of nutrients towards non-mammary tissues (Thering et al, 2009), studies in dairy goats characterising lipid metabolism in body tissues or nutritional regulation are still scant to assume that the same may happen in this species (Bernard et al, 2005a and.…”

Supplementation with corn oil and palm kernel oil to grazing cows: ruminal fermentation, milk yield, and fatty acid profile

“…Ruminal biohydrogenation of oils rich in linoleic acid (18:2 c9 c12 ) such as corn oil produces higher concentrations of TVA than oils rich in linolenic acid (18:3 c9 c12 c15 ) in vitro and in vivo (Matsushita et al, 2007;Castillo et al, 2012). In vivo, higher ruminal proportions of TVA have been associated with higher CLA and TVA milk proportions (Harvatine and Bauman, 2006).…”