PDF(Pubmed)
Abstract：
Ketosis, especially its subclinical form, is frequently observed in high-yielding dairy cows and is linked to various diseases during the transition period. Although adipose tissue plays a significant role in the development of metabolic disorders, its exact impact on the emergence of subclinical ketosis (SCK) is still poorly understood. The objectives of this study were to characterize and compare the profiling of transcriptome and lipidome of blood and adipose tissue between SCK and healthy cows and investigate the potential correlation between metabolic disorders and lipid metabolism. We obtained blood and adipose tissue samples from healthy cows (CON, n = 8, β-hydroxybutyric acid concentration < 1.2 mmol/L) and subclinical ketotic cows (SCK, n = 8, β-hydroxybutyric acid concentration = 1.2-3.0 mmol/L) for analyzing biochemical parameters, transcriptome, and lipidome. We found that serum levels of nonesterified fatty acids, malonaldehyde, serum amyloid A protein, IL-1β, and IL-6 were higher in SCK cows than in CON cows. Levels of adiponectin and total antioxidant capacity were higher in serum and adipose tissue from SCK cows than in CON cows. The top enriched pathways in whole blood and adipose tissue were associated with immune and inflammatory responses and sphingolipid metabolism, respectively. The accumulation of ceramide and sphingomyelin in adipose tissue was paralleled by an increase in genes related to ceramide biosynthesis, lipolysis, and inflammation and a decrease in genes related to ceramide catabolism, lipogenesis, adiponectin production, and antioxidant enzyme systems. Increased ceramide concentrations in blood and adipose tissue correlated with reduced insulin sensitivity. The current results indicate that the lipid profile of blood and adipose tissue is altered with SCK and that certain ceramide species correlate with metabolic health. Our research suggests that disruptions in ceramide metabolism could be crucial in the progression of SCK, exacerbating conditions such as insulin resistance, increased lipolysis, inflammation, and oxidative stress, providing a potential biomarker of SCK and a novel target for nutritional manipulation and pharmacological therapy.
摘要：
酮病,尤其是它的亚临床形式，在高产奶牛中经常观察到，并且在过渡时期与各种疾病有关。尽管脂肪组织在代谢紊乱的发展中起着重要作用，其对亚临床酮症(SCK)发生的确切影响尚不清楚.这项研究的目的是表征和比较SCK和健康奶牛之间血液和脂肪组织的转录组和脂质组的概况，并研究代谢紊乱和脂质代谢之间的潜在相关性。我们从健康奶牛中获取了血液和脂肪组织样本(CON，n=8，β-羟基丁酸浓度<1.2mmol/L）和亚临床酮症奶牛（SCK，n=8，β-羟基丁酸浓度=1.2-3.0mmol/L）用于分析生化参数，转录组，和脂腺。我们发现血清中的非酯化脂肪酸,丙二醛，血清淀粉样蛋白A,IL-1β,SCK奶牛的IL-6高于CON奶牛。SCK奶牛血清和脂肪组织中脂联素水平和总抗氧化能力高于CON奶牛。全血及脂肪组织中的最高富集途径与免疫和炎症反应以及鞘脂代谢相关,分别。神经酰胺和鞘磷脂在脂肪组织中的积累与神经酰胺生物合成相关的基因增加平行，脂解,炎症和神经酰胺分解代谢相关基因的减少，脂肪生成,脂联素的产生，和抗氧化酶系统。血液和脂肪组织中神经酰胺浓度增加与胰岛素敏感性降低相关。当前结果表明，SCK改变了血液和脂肪组织的脂质分布，并且某些神经酰胺种类与代谢健康相关。我们的研究表明，神经酰胺代谢的中断可能在SCK的进展中至关重要，恶化的条件，如胰岛素抵抗，脂解增加，炎症,和氧化应激，提供SCK的潜在生物标志物和营养操作和药物治疗的新目标。
