Molecular Response of Simmental Cows to Negative Energy Balance: Regulation of Interleukin-6 and Plasminogen During Early Lactation

Negative energy balance (NEB) during early lactation links spontaneous lipolysis (SL) with inflammatory signaling, yet the molecular response in dual-purpose breeds remains insufficiently characterized. This study investigated how NEB regulates circulating concentrations of interleukin-6 (IL-6) and plasminogen (PL) in Simmental cows, contextualizing these changes within concurrent metabolic adaptation. Forty-two cows were monitored from approximately two weeks prepartum to 150 days in milk across six defined stages. Energy balance (EB) was calculated from feed intake and energy-corrected milk yield, while daily milk production (DMP), milk composition, body condition score (BCS), β-hydroxybutyrate (BHBA), glucose (GLU), leptin (LEP), selected fatty acids (FAs: C16:0, C18:0, C18:1-t9, C18:2, IL-6), and PL were determined. EB declined progressively as DMP increased (r = −0.689, p ≤ 0.05). During peak NEB (SLII–SLIII), IL-6 increased from 92.16 to 109.59 ng·L−1 and PL from 1.65 to 2.05 ng·L−1, both inversely correlated with EB (r = −0.741 and −0.586, respectively) and positively associated with each other (r = 0.728), indicating coordinated activation of cytokine and fibrinolytic pathways. NEB severity was accompanied by elevated BHBA and LEP, decreased GLU, reduced BCS, and increased circulating FAs; nevertheless, ketosis remained moderate (peak BHBA 1.04 mmol·L−1). These findings demonstrate that Simmental cows display a breed-specific molecular response in which NEB modulates IL-6 and PL in parallel with controlled lipid mobilization and efficient hepatic metabolism, supporting enhanced metabolic resilience during early lactation.