Daudon Mathilde, Ramé Christelle, Estienne Anthony, Price Christopher, Dupont Joëlle
CNRS, IFCE, INRAE, Université de Tours, PRC, Breeding system and Animal Physiology Department, Nouzilly, France.
Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, Canada.
Front Vet Sci. 2022 Jul 27;9:960778. doi: 10.3389/fvets.2022.960778. eCollection 2022.
The peripartum period in dairy cows is frequently associated with excessive lipolysis due to Negative Energy Balance (NEB). These metabolic disorders are the cause of various pathologies. Some metabolites such as β-hydroxybutyrate (BHBA) and Non-Esterified Fatty Acids (NEFA) are known to be biomarkers of NEB in dairy cows. The involvement of adipokines, including adiponectin and leptin, during fat mobilization in the peripartum period is well described, but little is known about the impact of myokines at this time. Fibronectin type III domain-containing proteins (FNDC) are myokines and adipokines recently discovered to play a role in metabolic dysfunctions. This study aimed to evaluate some FNDCs (FNDC5, 4, 3A and B) as potential plasma and adipose tissue indicators of NEB in cattle. We measured plasma FNDC concentrations and adipose tissue FNDC gene expression during the peripartum period, 4 weeks before the estimated calving day (4WAP), one (1WPP) and 16 (16WPP) weeks postpartum in two groups of dairy cows with low NEB (LNEB, = 8) and high NEB (HNEB, = 13) at 1WPP. Using specific bovine ELISAs, only plasma FNDC5 concentrations varied during the peripartum period in both LNEB and HNEB animals; concentrations were higher at 1WPP as compared to 4WAP and 16 WPP. FNDC5 plasma concentrations was negatively correlated with dry matter intake, live body weight, variation of empty body weight and glucose concentrations, and positively correlated with plasma non-esterified fatty acids and BHBA concentrations. Subcutaneous adipose tissue contained abundant FNDC5 mRNA and protein, as measured by RT-qPCR and immunoblotting, respectively. We also observed that mRNA abundance in subcutaneous adipose tissue was higher at 1 WPP as compared to 4WAP and 16WPP in HNEB cows and higher at 1 WPP as compared to 4 WAP in LNEB cows, and was higher in HNEB than in LNEB animals during early lactation. Finally, we showed that recombinant human irisin (a fragmented product of FNDC5) increased the release of glycerol and abundance of mRNA encoding adipose triglyceride lipase and hormone-sensitive-lipase in bovine and human adipose tissue explants. In conclusion, FNDC5 is expressed in bovine adipose tissue and may be involved in lipid mobilization and regulation of NEB in cattle.
奶牛围产期常因能量负平衡（NEB）而出现过度脂肪分解。这些代谢紊乱是多种病理状况的原因。一些代谢物，如β-羟基丁酸（BHBA）和非酯化脂肪酸（NEFA），已知是奶牛NEB的生物标志物。在围产期脂肪动员过程中，包括脂联素和瘦素在内的脂肪因子的作用已有充分描述，但此时关于肌动蛋白的影响却知之甚少。含III型纤连蛋白结构域的蛋白（FNDC）是最近发现的在代谢功能障碍中起作用的肌动蛋白和脂肪因子。本研究旨在评估一些FNDC（FNDC5、4、3A和B）作为牛NEB潜在的血浆和脂肪组织指标。我们在两组围产期奶牛中测量了血浆FNDC浓度和脂肪组织FNDC基因表达，这两组奶牛在产后1周时分别具有低NEB（LNEB，n = 8）和高NEB（HNEB，n = 13），测量时间为预计产犊日前4周（4WAP）、产后1周（1WPP）和16周（16WPP）。使用特异性牛ELISA试剂盒，仅血浆FNDC5浓度在围产期的LNEB和HNEB动物中均有变化；与4WAP和16WPP相比，1WPP时浓度更高。FNDC5血浆浓度与干物质摄入量、活体体重、空腹体重变化和葡萄糖浓度呈负相关，与血浆非酯化脂肪酸和BHBA浓度呈正相关。通过RT-qPCR和免疫印迹分别检测发现，皮下脂肪组织含有丰富的FNDC5 mRNA和蛋白。我们还观察到，与4WAP和16WPP相比，HNEB奶牛在1WPP时皮下脂肪组织中的mRNA丰度更高，与4WAP相比，LNEB奶牛在1WPP时更高，并且在泌乳早期HNEB奶牛中的mRNA丰度高于LNEB奶牛。最后，我们表明重组人鸢尾素（FNDC5的一个片段产物）增加了牛和人脂肪组织外植体中甘油的释放以及编码脂肪甘油三酯脂肪酶和激素敏感性脂肪酶的mRNA丰度。总之，FNDC5在牛脂肪组织中表达，可能参与牛的脂质动员和NEB调节。
