Expression and Nutritional Regulation of Lipogenic Genes in the Ruminant Lactating Mammary Gland

Abstract

The effect of nutrition on milk fat yield and composition has largely been investigated in cows and goats, with some differences for fatty acid (FA) composition responses and marked species differences in milk fat yield response. Recently, the characterization of lipogenic genes in ruminant species allowed in vivo studies focused on the effect of nutrition on mammary expression of these genes, in cows (mainly fed milk fat-depressing diets) and goats (fed lipid-supplemented diets). These few studies demonstrated some similarities in the regulation of gene expression between the two species, although the responses were not always in agreement with milk FA secretion responses. A central role for trans-10 C18:1 and trans-10, cis-12 CLA as regulators of milk fat synthesis has been proposed. However, trans-10 C18:1 does not directly control milk fat synthesis in cows, despite the fact that it largely responds to dietary factors, with its concentration being negatively correlated with milk fat yield response in cows and, to a lesser extent, in goats. Milk trans-10, cis-12 CLA is often correlated with milk fat depression in cows but not in goats and, when postruminally infused, acts as an inhibitor of the expression of key lipogenic genes in cows. Recent evidence has also proven the inhibitory effect of the trans-9, cis-11 CLA isomer. The molecular mechanisms by which nutrients regulate lipogenic gene expression have yet to be well identified, but a central role for SREBP-1 has been outlined as mediator of FA effects, whereas the roles of PPARs and STAT5 need to be determined. It is expected that the development of in vitro functional systems for lipid synthesis and secretion will allow future progress toward (1) the identification of the inhibitors and activators of fat synthesis, (2) the knowledge of cellular mechanisms, and (3) the understanding of differences between ruminant species.

Role of trans fatty acids in the nutritional regulation of mammary lipogenesis in ruminants

“…Conversion of acetate to malonyl-CoA, catalyzed by ACC, is considered to be the ratelimiting step (Bauman and Davis, 1974). Recent studies have reported that expression of acyl-CoA synthetase short-chain family member ACSS2 gene increases in mammary tissue of cows during lactation, and that the changes in transcript Figure 4 Synthesis of milk fat in the bovine mammary epithelial cell (adapted from Bernard et al, 2008). Abbreviations: ACC, acetyl-CoA carboxylase; AGPAT, 1-acyl glycerol 3-phosphate acyl transferase; CD36, cluster of differentiation 36; CLD, cytoplasmic lipid droplet; CoA, coenzyme A; CM, chylomicron; DGAT, diacylglycerol acyltransferase 1; ER, endoplasmic reticulum; FA, fatty acid; FABP, fatty acid binding protein; FAS, fatty acid synthase; Glut 1, glucose transporter 1; GPAT, glycerol-3 phosphate acyl transferase; LPL, lipoprotein lipase; MFG, milk fat globule; SCD, stearoyl-CoA desaturase; TAG, triacylglyceride; VLDL, very low density-lipoprotein.…”

“…Studies in cows have revealed the occurrence of transcripts encoding for CD36 (Bionaz and Loor, 2008b) and several SLC27A isoforms (1, 2, 3, 5 and 6; Bionaz and Loor, 2008a) in mammary tissue and demonstrated that CD36 and SLC27A6 mRNA abundance increases during the first months of lactation (Bionaz and Loor, 2008b). Even though the mechanisms responsible for the transport of fatty acids across the capillary endothelium and interstitial space are not well characterized (Barber et al, 1997;Bernard et al, 2008), it has been suggested that SLC27A6, ACSL1 and FABP3 are involved in the coordinate regulation of channelling fatty acids towards milk fat TAG synthesis in the bovine mammary gland (Bionaz and Loor, 2008a).…”

“…Activity of SCD in the ruminant mammary gland is thought to occur as a mechanism to maintain and regulate the fluidity of milk to ensure efficient ejection from the mammary glands (Timmen and Patton, 1988). Stearoyl and palmitoyl-CoA are the preferred substrates for SCD with 18:0 to OA being the predominant precursor:product of SCD in the bovine mammary epithelial cell (bMEC) (Palmquist et al, 2005;Bernard et al, 2008). Between 49% and 60% of 18:0 available for mammary TAG synthesis is desaturated with the extent of endogenous conversion accounting for ca.…”

“…Numerous reviews have considered the effect of nutrition on milk fat synthesis in ruminants (Bauman and Griinari, 2003;Chilliard et al, 2007;Shingfield and Griinari, 2007), whereas several appraisals have considered possible molecular mechanisms underlying diet-induced changes in mammary lipogenesis and fat secretion Bernard et al, 2008;Harvatine et al, 2009a). In the following sections, the role of TFA formed during ruminal metabolism of dietary unsaturated fatty acids, lipogenic precursor supply and products of intermediary metabolism on milk fat secretion are examined.…”

Milk fat depression and energy balance in stall-fed dairy goats supplemented with increasing doses of conjugated linoleic acid methyl esters

“…The t10,c12-CLA isomer has demonstrated inhibition on the gene expression of the stearoyl-CoA desaturase enzyme (Baumgard et al, 2002b) and, in vivo, the enzyme activity on the mammary gland can be estimated through the product/ substrate ratio of some fatty-acid pairs under its action (Bernard et al, 2008). The absence of effect on c9,t11-CLA/ t11-18:1 ratio index could be because of the presence of the c9,t11-CLA isomer in the CLA supplement.…”