BACKGROUND Overgrazing is a major factor that causes steppe degradation in Inner Mongolian, resulting in extensive ecosystem damage. Scarcity of grass means sheep are smaller and therefore mutton and cashmere production is greatly reduced, which has resulted in massive annual economic losses. Liver is the primary metabolic organ in mammals. It is also the key source of energy supply and detoxification of metabolites in animals, has a close relationship with animal growth. However, investigations on the responses of sheep induced by consequence of overgrazing, particularly those relating to liver-related molecular mechanisms and related metabolic pathways, remain elusive. RESULTS The body weight daily gain of sheep, immune organ indices (liver and spleen), and serum parameters related to immune response, protein synthesis and energy supply (IgG, albumin, glucose and non-esterified fatty acid) were significantly lower in the overgrazing group. Other serum parameters including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen and interleukin-6 were significantly higher in the overgrazing group. For the RNA-Seq results, we identified approximately 50 differentially expressed genes, of which half of were up-regulated and the other half were down-regulated (overgrazing group versus light grazing group). Bioinformatics analysis identified two enriched KEGG pathways including peroxisome proliferator-activated receptor (PPAR) signaling pathway (related to lipolysis) and ECM-receptor interaction (related to liver injury and apoptosis). Additionally, several of the down-regulated genes were related to detoxification and immune response. CONCLUSIONS Overall, based on the high-throughput RNA sequencing profile integrated with the results of serum biochemical analyses, consequences of lower forage availability and quality under overgrazing condition induced altered expression levels of genes participating in energy metabolism (particularly lipid metabolism) and detoxification and immune responses, causing lipolysis and impaired health status, which might be key reasons for the reduced growth performance of sheep. This investigation provides a novel foundation for the development of sheep hepatic gene interactive networks that are a response to the degraded forage availability under overgrazing condition.

中文翻译：

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绵羊（Ovis aries）响应过度放牧的肝转录组概况：揭示了新的基因和途径。

背景技术过度放牧是导致内蒙古草原退化，导致广泛的生态系统破坏的主要因素。草的稀缺意味着绵羊较小，因此羊肉和羊绒的产量大大减少，从而造成了巨大的年度经济损失。肝脏是哺乳动物的主要代谢器官。它也是动物能量供应和代谢产物排毒的关键来源，与动物的生长有密切的关系。然而，对因过度放牧而引起的绵羊反应的研究，特别是与肝脏相关的分子机制和相关的代谢途径有关的研究，仍是可望而不可及的。结果绵羊的日增重，免疫器官指数（肝和脾）以及与免疫反应，蛋白质合成和能量供应（IgG，过度放牧组中白蛋白，葡萄糖和非酯化脂肪酸）显着降低。在过度放牧组中，其他血清参数包括丙氨酸转氨酶，天冬氨酸转氨酶，碱性磷酸酶，总胆红素，血尿素氮和白介素-6均显着较高。对于RNA-Seq结果，我们鉴定了大约50个差异表达的基因，其中一半被上调，另一半被下调（过度放牧组与轻度放牧组）。生物信息学分析确定了两个丰富的KEGG途径，包括过氧化物酶体增殖物激活受体（PPAR）信号传导途径（与脂解有关）和ECM-受体相互作用（与肝损伤和细胞凋亡有关）。此外，一些下调的基因与排毒和免疫反应有关。结论总体而言，基于高通量RNA测序图谱与血清生化分析结果相结合，在过度放牧条件下降低草料利用率和质量的后果导致参与能量代谢（尤其是脂质代谢），排毒和免疫的基因表达水平改变反应，导致脂肪分解和健康状况受损，这可能是绵羊生长性能下降的关键原因。这项研究为绵羊肝基因相互作用网络的发展提供了新的基础，该网络是对过度放牧条件下退化的牧草可利用性的反应。过度放牧条件下牧草供应量和质量降低的后果导致参与能量代谢（尤其是脂质代谢），排毒和免疫反应的基因表达水平改变，导致脂肪分解和健康状况受损，这可能是绵羊生长性能下降的关键原因。这项研究为绵羊肝基因相互作用网络的发展提供了新的基础，该网络是对过度放牧条件下退化的牧草可利用性的反应。过度放牧条件下牧草供应量和质量降低的后果导致参与能量代谢（尤其是脂质代谢），排毒和免疫反应的基因表达水平改变，导致脂肪分解和健康状况受损，这可能是绵羊生长性能下降的关键原因。这项研究为绵羊肝基因相互作用网络的发展提供了新的基础，该网络是对过度放牧条件下退化的牧草可利用性的反应。