Bionaz Massimo, Loor Juan J
Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, 61801 Illinois, USA.
BMC Genomics. 2008 Jul 31;9:366. doi: 10.1186/1471-2164-9-366.
The molecular events associated with regulation of milk fat synthesis in the bovine mammary gland remain largely unknown. Our objective was to study mammary tissue mRNA expression via quantitative PCR of 45 genes associated with lipid synthesis (triacylglycerol and phospholipids) and secretion from the late pre-partum/non-lactating period through the end of subsequent lactation. mRNA expression was coupled with milk fatty acid (FA) composition and calculated indexes of FA desaturation and de novo synthesis by the mammary gland.
Marked up-regulation and/or % relative mRNA abundance during lactation were observed for genes associated with mammary FA uptake from blood (LPL, CD36), intracellular FA trafficking (FABP3), long-chain (ACSL1) and short-chain (ACSS2) intracellular FA activation, de novo FA synthesis (ACACA, FASN), desaturation (SCD, FADS1), triacylglycerol synthesis (AGPAT6, GPAM, LPIN1), lipid droplet formation (BTN1A1, XDH), ketone body utilization (BDH1), and transcription regulation (INSIG1, PPARG, PPARGC1A). Change in SREBF1 mRNA expression during lactation, thought to be central for milk fat synthesis regulation, was < or =2-fold in magnitude, while expression of INSIG1, which negatively regulates SREBP activation, was >12-fold and had a parallel pattern of expression to PPARGC1A. Genes involved in phospholipid synthesis had moderate up-regulation in expression and % relative mRNA abundance. The mRNA abundance and up-regulation in expression of ABCG2 during lactation was markedly high, suggesting a biological role of this gene in milk synthesis/secretion. Weak correlations were observed between both milk FA composition and desaturase indexes (i.e., apparent SCD activity) with mRNA expression pattern of genes measured.
A network of genes participates in coordinating milk fat synthesis and secretion. Results challenge the proposal that SREBF1 is central for milk fat synthesis regulation and highlight a pivotal role for a concerted action among PPARG, PPARGC1A, and INSIG1. Expression of SCD, the most abundant gene measured, appears to be key during milk fat synthesis. The lack of correlation between gene expression and calculated desaturase indexes does not support their use to infer mRNA expression or enzyme activity (e.g., SCD). Longitudinal mRNA expression allowed development of transcriptional regulation networks and an updated model of milk fat synthesis regulation.
与奶牛乳腺中乳脂肪合成调控相关的分子事件仍 largely 未知。我们的目标是通过定量 PCR 研究乳腺组织中 45 个与脂质合成（三酰甘油和磷脂）及从产前后期/非泌乳期到随后泌乳期末的分泌相关基因的 mRNA 表达。mRNA 表达与乳脂肪酸（FA）组成以及乳腺 FA 去饱和及从头合成的计算指数相关联。
在泌乳期间，观察到与从血液摄取乳腺 FA（LPL、CD36）、细胞内 FA 转运（FABP3）、长链（ACSL1）和短链（ACSS2）细胞内 FA 活化、FA 从头合成（ACACA、FASN）、去饱和（SCD、FADS1）、三酰甘油合成（AGPAT6、GPAM、LPIN1）、脂滴形成（BTN1A1、XDH）、酮体利用（BDH1）以及转录调控（INSIG1、PPARG、PPARGC1A）相关的基因有显著上调和/或相对 mRNA 丰度百分比增加。泌乳期间 SREBF1 mRNA 表达的变化，被认为是乳脂肪合成调控的核心，幅度小于或等于 2 倍，而负向调节 SREBP 活化的 INSIG1 的表达则大于 12 倍，并且与 PPARGC1A 具有平行的表达模式。参与磷脂合成的基因在表达及相对 mRNA 丰度百分比方面有适度上调。泌乳期间 ABCG2 的 mRNA 丰度及表达上调显著，表明该基因在乳汁合成/分泌中具有生物学作用。在测得的基因 mRNA 表达模式与乳 FA 组成和去饱和酶指数（即表观 SCD 活性）之间观察到弱相关性。
一个基因网络参与协调乳脂肪的合成与分泌。结果对 SREBF1 是乳脂肪合成调控核心的提议提出了挑战，并突出了 PPARG、PPARGC1A 和 INSIG1 协同作用的关键作用。所测最丰富基因 SCD 的表达似乎在乳脂肪合成过程中起关键作用。基因表达与计算的去饱和酶指数之间缺乏相关性不支持用它们来推断 mRNA 表达或酶活性（例如 SCD）。纵向 mRNA 表达有助于构建转录调控网络以及更新乳脂肪合成调控模型。
