Abstract
BackgroundIn dairy cows, the periparturient phase is a stressful period, which is commonly associated with strong metabolic adaptations and the development of pathophysiologic conditions and disorders. Some of the symptoms occurring in the liver, such as the development of fatty liver, are similar to those observed under the condition of endoplasmic reticulum (ER) stress. Therefore, we hypothesized, that in the liver of dairy cows ER stress is induced during the periparturient phase, which in turn leads to an induction of the unfolded protein response (UPR). In order to investigate this hypothesis, we determined relative mRNA concentrations of 14 genes of the ER stress-induced UPR in liver biopsy samples of 13 dairy cows at 3 wk antepartum and 1, 5 and 14 wk postpartum.ResultsWe found, that the mRNA concentrations of 13 out of the 14 genes involved in the UPR in the liver were significantly increased (1.9 to 4.0 fold) at 1 wk postpartum compared to 3 wk antepartum. From 1 wk postpartum to later lactation, mRNA concentrations of all the genes considered were declining. Moreover, at 1 wk postpartum, mRNA concentration of the spliced variant of XBP1 was increased in comparison to 3 wk antepartum, indicating that splicing of XBP1 – a hallmark of ER stress - was induced following the onset of lactation.ConclusionThe present study reveals, that ER stress might be induced during the periparturient phase in the liver of dairy cows. We assume that the ER stress-induced UPR might contribute to the pathophysiologic conditions commonly observed in the liver of periparturient cows, such as the development of fatty liver, ketosis or inflammation.
Highlights
In dairy cows, the periparturient phase is a stressful period, which is commonly associated with strong metabolic adaptations and the development of pathophysiologic conditions and disorders
Plasma non-esterified fatty acids (NEFA) concentrations showed their peak values at 1 wk postpartum while plasma β-hydroxybutyric acid (BHBA) concentrations were highest at 1 wk and 5 wk postpartum
The cows considered in this study, showed increased mRNA concentrations of tumor necrosis factor α and acute phase proteins (C-reactive protein, haptoglobin, serum amyloid A) being indicative of a pro-inflammatory condition and increased mRNA concentrations of various nuclear factor E2-related factor 2 (Nrf2) target genes and of FGF21 in the liver at 1 wk postpartum [35,36]
Summary
The periparturient phase is a stressful period, which is commonly associated with strong metabolic adaptations and the development of pathophysiologic conditions and disorders. We hypothesized, that in the liver of dairy cows ER stress is induced during the periparturient phase, which in turn leads to an induction of the unfolded protein response (UPR). During early lactation, dairy cows are typically in a negative energy balance, which is compensated by a stimulation of lipolysis in adipose tissue. This leads to strongly increased plasma concentrations of non-esterified fatty acids (NEFA), which are partially taken up into the liver. There is commonly a strong stimulation of ketogenesis during early lactation, which can result in ketosis [1,2,3]
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