Subacute ruminal acidosis (SARA) of dairy cattle is a widely occurring but not very overt metabolic disorder thought to impair milk composition. The enzyme stearoyl-CoA desaturase 1 (SCD1) is rate-limiting for the formation of Δ-9 unsaturated fatty acids and thus crucially involved in controlling lipid metabolism in the liver. It is known that SCD1 expression is downregulated during SARA, but the underlying molecular mechanisms are unknown. To study these mechanisms, we enrolled 12 healthy multiparous mid-lactation Holstein cows into a diet-induced SARA experiment. Six cows were fed a high-concentrate diet for 18 weeks (60% content of high-concentrate to 40% forage; HC group), whereas the others received a low-concentrate diet ad libitum (40% high-concentrate content to 60% forage; LC group). Sustained low ruminal pH values (pH 5.6 maintained for 4 h/d) and reduced milk yield performance (2.07 kg/d less than LC cows) verified that SARA had been induced in the HC group. Results showed a significantly decreased concentrations of cis-9 monounsaturated long-chain fatty acids in plasma collected from hepatic but not portal veins. This was matched by reduced SCD1 mRNA and protein concentrations in HC livers. The expression levels of genes related to lipid formation (DGAT1 and PLIN2) were downregulated during SARA, whereas those of catabolic genes (CPT1A, CPT2, and ACOX1) and some inflammatory genes were upregulated. Expression of SCD1 was downregulated through reduced transcription and abundance of the transcription factor sterol regulatory element-binding protein 1 (SREBP1c). This effect was augmented by local chromatin tightening and DNA methylation at and around the SREBP1c binding site in the SCD1 promoter. Chromatin immunoprecipitation assays confirmed that SARA reduced SREBP1c binding at the SCD1 promoter; hence, epigenetic mechanisms are involved in regulating the expression of genes related to long-chain fatty acid modification, partially through downregulation of both SCD1 and SREBP1c in the liver. Our results suggest that in addition to inflammatory genes, SCD1 is also involved in SARA-induced epigenetic regulation and its associated metabolic changes. This knowledge might help to provide a target for intervening against the detrimental metabolic effects of SARA.

奶牛的亚急性瘤胃酸中毒（SARA）是一种广泛存在但不是很明显的代谢紊乱，被认为会损害牛奶成分。硬脂酰辅酶A去饱和酶1（SCD1）酶是Δ-9不饱和脂肪酸形成的限速酶，因此至关重要地参与了肝脏脂质代谢的控制。已知在SARA期间SCD1表达下调，但是潜在的分子机制尚不清楚。为了研究这些机制，我们将12头健康的多胎哺乳中期荷斯坦奶牛纳入了饮食诱导的SARA实验。6头奶牛饲喂高浓度饮食18周（高浓度60％至40％的草料； HC组），而其他母牛则随意接受低浓度饮食（40％高浓度至60％的饲粮）草料； LC组）。瘤胃pH值持续较低（pH 5。6头维持4 h / d）和降低的产奶性能（比LC奶牛低2.07 kg / d）证实HC组诱导了SARA。结果显示浓度显着降低血浆中的顺式-9单不饱和长链脂肪酸是从肝脏采集的，但不是从门静脉采集的。这与HC肝脏中SCD1 mRNA和蛋白质浓度降低相匹配。在SARA期间，与脂质形成相关的基因（DGAT1和PLIN2）的表达水平下调，而分解代谢基因（CPT1A，CPT2和ACOX1）和一些炎症基因的表达水平上调。通过减少转录和丰富的转录因子固醇调节元件结合蛋白1（SREBP1c），SCD1的表达被下调。通过在SREBP1c结合位点及其周围的局部染色质紧缩和DNA甲基化增强了这种作用。SCD1启动子。染色质免疫沉淀试验证实，SARA减少了SCD1启动子上SREBP1c的结合；因此，表观遗传机制参与调节与长链脂肪酸修饰有关的基因的表达，部分是通过肝脏中SCD1和SREBP1c的下调来实现的。我们的结果表明，除炎症基因外，SCD1还参与SARA诱导的表观遗传调控及其相关的代谢变化。这些知识可能有助于提供干预目标，以抵御SARA的有害代谢作用。