Performance and Metabolic, Inflammatory, and Oxidative Stress-Related Parameters in Early Lactating Dairy Cows with High and Low Hepatic FGF21 Expression

SIMPLE SUMMARY: Studies with rodent models have shown that fibroblast growth factor 21 (FGF21) is a metabolic regulator induced in the liver in response to different stress conditions, such as energy and nutrient deprivation, inflammation, and metabolic disorders. Recently, it has been found that hepatic FGF21 expression is strongly upregulated in dairy cows during early lactation. However, the function of FGF21 in cows has not yet been established. Therefore, the aim of the present study was to gain knowledge about the physiological role played by FGF21 in cows during this period. To this end, out of 30 cows, 8 cows with the highest hepatic FGF21 expression were compared to 8 cows with the lowest hepatic FGF21 expression. Cows with high and low hepatic FGF21 expression did not differ in milk yield, feed intake, nor energy balance. Transcriptomics screening, targeted plasma metabolomics, and analyses of antioxidant parameters indicated that high hepatic FGF21 expression was related to endoplasmic reticulum stress and induction of the antioxidative system in the livers of dairy cows. Therefore, the data of this study suggest that FGF21 plays an important role in the adaptation to cellular stress conditions in early lactation when cows are typically confronted with several stress stimuli. ABSTRACT: Induction of FGF21 expression in the liver and a significant increase in plasma FGF21 concentration have been demonstrated in cows during early lactation, but knowledge about the function of FGF21 in dairy cows remains limited. In order to improve the understanding of the physiological role of FGF21 in dairy cows, the present study aimed to investigate differences in metabolic pathways between dairy cows with high and low hepatic expression of FGF21 at week 1 of lactation (n = 8/group) by liver transcriptomics, targeted plasma metabolomics, and analysis of inflammatory and oxidative stress-related parameters. Dry matter intake, energy balance, milk yield, and energy-corrected milk yield at days 8–14 postpartum did not differ between cows with high and low hepatic FGF21 expression. However, cows with high FGF21 expression showed an upregulation of genes involved in endoplasmic reticulum stress, inflammation, and nuclear factor E2-related factor 2 (Nrf2)-dependent cytoprotection compared to cows with low FGF21 expression at week 1 postpartum (p < 0.05). Concentrations of important antioxidants (tocopherols, β-carotene, and glutathione) in the liver and plasma, trolox equivalent antioxidant capacity in plasma, concentrations of oxidative stress-related compounds (thiobarbituric acid-reactive substances and protein carbonyls), and levels of most acute phase proteins at week 1 postpartum did not differ between cows with high or low FGF21 expression. Moreover, among a total of >200 metabolites assayed in the plasma, concentrations of only 7 metabolites were different between cows with high or low FGF21 expression (p < 0.05). Overall, the results showed that cows with high and low FGF21 hepatic expression had only moderate differences in metabolism, but FGF21 might be important in the adaptation of dairy cows to stress conditions during early lactation.