Investigations on the reasons of stress of the endoplasmic reticulum (ER stress) in the liver of dairy cows in early lactation and the role of ER stress in the development of fatty liver syndrome and ketosis

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For high yielding dairy cows, the periparturient phase represents a stressful condition which is associated with a high metabolic demand and an increased risk of various metabolic diseases. Among metabolic diseases, fatty liver syndrome and ketosis are most relevant. These diseases are also of particular relevance as they are associated with the development of several other diseases and an impairment of fertility. Therefore, the prevention of fatty liver and ketosis has high priority. Because pathogenesis of these diseases has been clarified only in part, a better understanding of biochemical reasons underlying the development of fatty liver and ketosis is required. Based on our own preliminary studies, the applied project aims to investigate the hypothesis that stress of the endoplasmic reticulum (ER stress), a phenomenon we could recently demonstrate to occur in the liver of high-yielding cows in early lactation, plays a central role in the development of fatty liver and ketosis (hypothesis I). As the reasons underlying the development of ER stress in the liver have not yet been unraveled, the project further aims to investigate the hypothesis that ER stress is caused by (I) high levels of non-esterified fatty acids (NEFA) in Plasma, (II) the occurrence of an inflammation process in the liver, (III) oxidative stress, (IV) high concentrations of lipopolysaccharides (LPS) in plasma (hypothesis II). For investigating these hypotheses, liver biopsy samples and plasma samples which were collected from 50 Holstein cows at 2 weeks ante partum, 1 week post partum, 4 weeks post partum and 7 weeks post partum can be used. In order to investigate hypothesis I, correlations between various markers of ER stress in liver samples and concentrations of triglycerides in liver samples or concentrations of ß-hydroxy butyrate will be determined. In order to investigate hypothesis II, correlations between (I) plasma NEFA concentrations, (II) inflammatory markers in the liver, (III) parameters of oxidative stress in plasma (IV) plasma concentrations of LPS and markers of ER stress in the liver will be calculated. We expect from these investigations that they will provide a better understanding of the reasons underlying ER stress in the liver of dairy cows in early lactation and the role of ER stress in the development of fatty liver and ketosis. Proving a central role of ER stress in the development of fatty liver and ketosis would offer new perspectives in the prevention of these diseases in dairy cows.