Dairy cows exhibit a specific physiological state during the transition from late pregnancy to early lactation. This period is characterized by metabolic and immunological alterations to sustain increased energy needs. Interleukin-15 (IL-15) is a well-known anabolic cytokine that regulates energy expenditure in muscle tissue. This study aimed to investigate the role of IL-15 in the metabolic adaptation of dairy cows during the transition period. Thirty-four Holstein-Friesian cows were included in this study. Blood samples were collected twice: three weeks prepartum and three weeks postpartum from all animals to estimate β-HB and non-esterified fatty acids (NEFA) concentrations using ELISA, in addition to IL-15 and Glucose-regulated protein 78 (GRP78) gene expression. Cows are considered to be at normal status or in negative energy balance (NEB) when β-HB is <1.4 mmol/L or β-HB >1.4 mmol/L, respectively. The results of our study revealed that β-HB concentrations are higher significantly (p = 0.0001) in NEB than in normal-status cows, both prepartum and postpartum. Similar results were observed regarding NEFA concentration in NEB compared with that in normal-status cows. However, this increase in NEFA concentration did not reach a significant level both prepartum (p = 0.100) and postpartum (p = 0.141). In addition, NEB cows showed significant downregulation of IL-15 expression levels (p = 0.003) compared with normal-status cows postpartum. There were no significant (p = 0.934) differences in IL-15 expression levels between the two groups prepartum. Furthermore, the results showed that GRP78 expression levels were significantly upregulated in NEB compared to normal-status cows both prepartum (p = 0.010) and postpartum (p = 0.034). The body may downregulate IL-15 as a cost-saving immune adaptation. These findings indicate the pivotal physiological role of IL-15 in the regulation of postpartum energy expenditure and metabolic adaptation. Furthermore, the results showed that GRP78 expression levels were upregulated in NEB cows both pre- and postpartum as a part of metabolic adaptation in the transition period.
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