Michelotti Tainara C, Menarim Bruno C, Tegeler Alexandra P, Fiallo Diez Jean F, Machado Vinicius S, Jones-Hall Yava, Benitez Oscar J, Loux Shavahn C, Strieder-Barboza Clarissa
Department of Veterinary Sciences, Davis College of Agricultural Sciences and Natural Resources, Texas Tech University, Lubbock, TX, United States.
Gluck Equine Research Center, Department of Veterinary Sciences, Martin-Gatton College of Agricultural, Food and Environment, University of Kentucky, Lexington, KY, United States.
Front Immunol. 2025 Jun 17;16:1578669. doi: 10.3389/fimmu.2025.1578669. eCollection 2025.
Subclinical ketosis (SCK) is a common metabolic disorder linked to adipose tissue (AT) dysfunction in periparturient dairy cows. While subcutaneous AT (SAT) and visceral AT (VAT) differ in structure, cellularity, and function, depot-specific responses to ketosis remain poorly understood. This study aimed to determine the transcriptional differences of flank SAT and omental VAT in early lactation dairy cows in response to SCK.
Multiparous Holstein dairy cows within the first 10 days postpartum were screened for SCK. Subclinical ketosis was defined as blood β-hydroxybutyrate (BHB) concentrations between 1.4 and 2.6 mmol/L, while control, non-ketotic animals (NK) had BHB equal to or lower than 0.8 mmol/L. Adipose tissue biopsies were obtained from flank SAT and omental VAT from five SCK and five NK cows for RNA sequencing and immunohistochemistry analyses.
Subclinical ketosis affected AT transcriptional profiles in a depot-specific manner. In SAT, transcriptional changes related to SCK reflected homeostatic AT remodeling and immune cell infiltration indicative of inflammatory responses, fibroplasia, and the negative regulation of adaptive immunity responses. In VAT, SCK-related transcriptional changes reflected increased pro-inflammatory responses linked to impaired lipid metabolism and dysregulation of focal adhesion and endocytosis. Tissue expression of proteins coded by genes differentially expressed between SCK and NK revealed a depot-dependent response on AT, indicating a higher infiltration of macrophages and B cells in SCK cows. Overall, our study provides new insights into molecular mechanisms underlying ketosis pathogenesis, highlighting the dysregulation of inflammatory responses, lipid metabolism, and insulin signaling in both SAT and VAT of postpartum dairy cows.
亚临床酮病（SCK）是围产期奶牛中一种常见的代谢紊乱疾病，与脂肪组织（AT）功能障碍有关。虽然皮下脂肪组织（SAT）和内脏脂肪组织（VAT）在结构、细胞组成和功能上存在差异，但不同脂肪库对酮病的特异性反应仍知之甚少。本研究旨在确定早期泌乳奶牛的胁腹SAT和网膜VAT在应对SCK时的转录差异。
对产后10天内的经产荷斯坦奶牛进行SCK筛查。亚临床酮病定义为血液β-羟基丁酸（BHB）浓度在1.4至2.6 mmol/L之间，而对照的非酮病动物（NK）的BHB浓度等于或低于0.8 mmol/L。从5头SCK奶牛和5头NK奶牛的胁腹SAT和网膜VAT获取脂肪组织活检样本，进行RNA测序和免疫组织化学分析。
亚临床酮病以脂肪库特异性方式影响AT转录谱。在SAT中，与SCK相关的转录变化反映了脂肪组织的稳态重塑以及免疫细胞浸润，提示炎症反应、纤维组织增生和适应性免疫反应的负调控。在VAT中，与SCK相关的转录变化反映了促炎反应增加，这与脂质代谢受损、粘着斑失调和内吞作用异常有关。SCK和NK之间差异表达基因编码的蛋白质的组织表达显示了AT的脂肪库依赖性反应，表明SCK奶牛中巨噬细胞和B细胞的浸润更高。总体而言，我们的研究为酮病发病机制的分子机制提供了新见解，突出了产后奶牛SAT和VAT中炎症反应、脂质代谢和胰岛素信号传导的失调。
