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

泌乳早期奶牛肝脏内质网应激（ER应激）原因及其在脂肪肝综合征和酮病发生中的作用探讨

• 批准号: 321274540
• 负责人: Dr. Denise Geßner
• 金额: --
• 依托单位: Institut für Tierernährung & Ernährungsphysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/321274540?language=en
• 关键词: Investigations; reasons; stress; endoplasmic; reticulum

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.

对于高产奶牛而言，围产期是一种应激状态，与高代谢需求和各种代谢疾病风险增加有关。在代谢性疾病中，脂肪肝综合征和酮症是最相关的。这些疾病也特别相关，因为它们与其他几种疾病的发展和生育能力的损害有关。因此，预防脂肪肝和酮症具有高度优先性。由于这些疾病的发病机制只得到部分澄清，需要更好地了解脂肪肝和酮症发展的生化原因。基于我们自己的初步研究，应用项目旨在研究内质网应激（ER应激）的假设，我们最近可以证明在泌乳早期高产奶牛的肝脏中发生的现象，在脂肪肝和酮病的发展中起着核心作用（假设I）。由于肝脏中ER应激发展的根本原因尚未阐明，该项目进一步旨在研究ER应激由以下因素引起的假设：（I）血浆中高水平的非酯化脂肪酸（NEFA），（II）肝脏中炎症过程的发生，（III）氧化应激，（IV）血浆中高浓度的脂多糖（LPS）（假设II）。为了研究这些假设，可以使用从50头荷斯坦奶牛在产前2周、产后1周、产后4周和产后7周收集的肝活检样品和血浆样品。为了研究假设I，将确定肝脏样品中ER应激的各种标志物与肝脏样品中甘油三酯浓度或β-羟基丁酸酯浓度之间的相关性。为了研究假设II，将计算（I）血浆NEFA浓度、（II）肝脏中的炎性标志物、（III）血浆中的氧化应激参数（IV）LPS的血浆浓度和肝脏中的ER应激标志物之间的相关性。我们期望从这些调查，他们将提供一个更好地了解的原因ER应激在奶牛的肝脏在泌乳早期和ER应激的作用，在脂肪肝和酮病的发展。证明ER应激在脂肪肝和酮病的发展中的核心作用将为奶牛预防这些疾病提供新的视角。