Lipogenic gene network expression in mammary tissue in response to abomasal infusion of casein, glucose and acetate into feed-restricted lactating cows

Abstract Text: Nutrients that are building blocks of the main milk components also can work as regulators of the synthesis of these products through cell signaling pathways regulated at the transcriptional level. Six Holstein multiparous cows, averaging 40 kg milk/d, were used in a 6x6 Latin square with 14-d periods. Cows were fed the same diet for 10 days in each period, after which they were feed-restricted for 4 days to 85% of ad libitum intake and abomasally-infused with 1 of 6 treatments: acetate (A), glucose (G), each at 5% of ad libitum metabolizable energy intake (Mcal/d), casein (C) at 15% of ad libitum metabolizable protein intake (g/d), A+C (AC), G+C (GC), or a saline solution (S, negative control). The mean milk fat yield was 1.58, 1.55, 1.42, 1.65, 1.51, 1.41 kg/d for A, G, C, AC, GC, and S, respectively. Mammary tissue was biopsied on the last day of each period. The expression of lipogenic gene networks was evaluated via quantitative RT-PCR of 11 genes. Data were log2-transformed and analyzed using the GLIMMIX procedure of SAS. Infusion of all nutrients up-regulated (P < 0.05) ACSS2, ACACA, and FASN, which are involved in acetate activation and de novo fatty acid (FA) synthesis. Surprisingly, A alone did not cause a greater effect than C and G, but when AC was infused the expression of these genes was the greatest (~2-3-fold greater), suggesting a role of amino acids in regulating FA synthesis. This was even more evident in the up-regulation (P < 0.05) by AC of FABP3, encoding a cytosolic transport protein required for use of FA in triacylglycerol synthesis. Acetate and AC up-regulated IDH1 (~2-5 fold), which encodes the main enzyme responsible for NADPH synthesis in mammary cells. This response agreed with the gene data indicating an overall stimulation of FA synthesis especially in the AC treatment. There was no treatment effect (P > 0.05) on AGPAT6, DGAT1, LPIN1, and PPARG. Unexpectedly, A down-regulated (P < 0.05) the lipogenic transcription factor SREBF1, which has previously been associated with FA synthesis regulation in mammary tissue during milk fat depression. However, the fact that AC induced a strong tendency (P = 0.08) for upregulation (2-fold) of the transcription regulator RXRA compared with S underscores a potentially-important role in the nutritional-regulation of milk fat synthesis. Results underscore the role of nutrients in regulating mammary FA synthesis at the transcriptional level.

Keywords: milk fat synthesis, nutrigenomics