围产期奶牛高NEFA血症对脂肪组织脂代谢和分泌机能的影响

Fat mobilization caused by negative energy balance is an important physiological adaptation mechanism in perinatal dairy cows, and the high-level non-esterified fatty acid (NEFA) is the main clinical pathological feature. Low levels of energy metabolism-related factors adiponectin (ADPN), leptin (LP) and high level of inflammatory factors TNFα, IL-6 are closely associated with the occurrence of ketosis, fatty liver, mastitis and endometritis in dairy cows with high NEFA levels. Therefore, we hypothesized that high levels of NEFA might interfere with the lipid metabolism and cytokines secretion of adipose tissue, thereby increase the occurrence of energy metabolism diseases and infectious diseases in perinatal dairy cows. This study is carried out both in dairy cows with high level of NEFA and cultured adipocytes in vitro. The signaling pathways of NEFA on the gene expression and activity of the key enzymes involved in the lipid metabolism as well as secretion of the cytokines factors and inflammatory factors in adipose tissues will be investigated. The interaction relationship between lipid metabolism and secretion function of the adipose tissue will be further analyzed. This study aimed to assess plausible mechanisms of NEFA to the lipid metabolism and secretion function of the adipose tissue, and to lay groundwork for the prevention of negative energy balance diseases in perinatal dairy cows through controlling fat mobilization.

能量负平衡所引起的脂肪动员是围产期奶牛重要的生理适应机制，高非酯化脂肪酸（NEFA）血症则是其主要临床病理学特征。而高NEFA血症奶牛存在的低水平脂联素（ADPN）、瘦素（LP）等能量代谢相关因子和高水平TNFα、IL-6等炎性因子与酮病、脂肪肝、乳房炎、子宫内膜炎等围产期疾病的发生密切相关。因此，本项目提出高NEFA血症可能干扰脂肪组织脂代谢和分泌机能，进而影响围产期奶牛能量代谢障碍性疾病和感染性疾病发生的科学假设。本研究拟通过高NEFA血症病牛在体实验和体外脂肪细胞实验，观测高NEFA对奶牛脂肪组织脂代谢关键酶表达和活性的调节作用及信号通路；检测高NEFA对脂肪细胞因子和炎性因子基因表达和分泌的调节作用及信号机制；分析高NEFA状态下脂肪组织脂代谢与分泌机能的互作关系，以期揭示NEFA对脂肪组织脂代谢和分泌机能的调节机制，为采用缓解脂肪动员防治奶牛围产期能量负平衡性疾病奠定理论基础。

奶牛围产期干物质摄入量降低，能量需求升高，为满足奶牛自身及泌乳能量需求，脂肪组织的大量动员在此期间发挥着重要作用。然而，强烈持久的脂解作用可抑制脂肪组织的能量缓冲能力并增加促炎细胞因子分泌，使围产期奶牛继发营养代谢及感染性疾病。因此，本项目的主要研究内容为探究围产期能量负平衡奶牛脂肪组织脂代谢、分泌机能及氧化应激的特征，并探究其具体的调控机制。本项目通过对泌乳初期酮病和健康奶牛脂肪组织的转录组和蛋白组测序，发现酮病奶牛脂肪组织中可能产生多种功能性lncRNA，通过与mRNA相互作用调节蛋白表达，影响酮病奶牛脂肪组织的脂代谢、炎症反应和氧化应激等过程。体外脂肪细胞过表达PLIN1或激活GPR120上调SREBP-1c及其下游脂合成基因的表达，下调脂解基因的表达，引起TG蓄积。沉默PLIN1或GPR120下调脂合成基因的表达，上调脂解基因的表达，缓解TG蓄积。同时，过表达PLIN1、TGFβ1或激活GPR120抑制NF-κB信号通路，降低LPS引起的炎性因子表达。沉默PLIN1、TGFβ1或GPR120可激活NF-κB信号通路，促进LPS引起的炎性因子表达。另外，脂肪细胞过表达HSPB7改善H2O2诱导的氧化应激，沉默HSPB7加剧H2O2诱导的氧化应激。本项目研究结果明确了高 NEFA 血症奶牛体内的代谢特征，以及奶牛脂肪细胞脂代谢、分泌机能及氧化应激的具体信号机制，为通过缓解脂肪动员预防围产期能量代谢障碍性疾病、乳房炎和子宫内膜炎等炎性疾病提供理论基础。

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