Zhao Huiying, Li Liuxue, Tan Jian, Wang Ying, Zhang Ao, Zhao Yuchao, Jiang Linshu
Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China.
Antioxidants (Basel). 2024 May 17;13(5):614. doi: 10.3390/antiox13050614.
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.
酮血症,尤其是亚临床酮血症,在高产奶牛中经常出现,并且与围产期的各种疾病有关。尽管脂肪组织在代谢紊乱的发展中起着重要作用,但其对亚临床酮血症(SCK)发生的确切影响仍知之甚少。本研究的目的是表征和比较SCK奶牛与健康奶牛血液和脂肪组织的转录组和脂质组图谱,并研究代谢紊乱与脂质代谢之间的潜在相关性。我们从健康奶牛(CON,n = 8,β-羟基丁酸浓度<1.2 mmol/L)和亚临床酮血症奶牛(SCK,n = 8,β-羟基丁酸浓度= 1.2 - 3.0 mmol/L)获取血液和脂肪组织样本,以分析生化参数、转录组和脂质组。我们发现,SCK奶牛血清中的非酯化脂肪酸、丙二醛、血清淀粉样蛋白A、IL-1β和IL-6水平高于CON奶牛。SCK奶牛血清和脂肪组织中的脂联素水平和总抗氧化能力高于CON奶牛。全血和脂肪组织中富集程度最高的通路分别与免疫和炎症反应以及鞘脂代谢有关。脂肪组织中神经酰胺和鞘磷脂的积累与神经酰胺生物合成、脂肪分解和炎症相关基因的增加以及神经酰胺分解代谢、脂肪生成、脂联素产生和抗氧化酶系统相关基因的减少同时出现。血液和脂肪组织中神经酰胺浓度的增加与胰岛素敏感性降低相关。目前的结果表明,SCK会改变血液和脂肪组织的脂质谱,并且某些神经酰胺种类与代谢健康相关。我们的研究表明,神经酰胺代谢紊乱可能在SCK的进展中起关键作用,加剧胰岛素抵抗、脂肪分解增加、炎症和氧化应激等状况,为SCK提供了一个潜在的生物标志物以及营养调控和药物治疗的新靶点。