A Proteomic-Based Identification of Biomarkers for Hepatic Lipidosis - A Comparative Approach with Focus on Cattle and Pigs
Background
Hepatic lipidosis (fatty liver) is a metabolic disorder characterized by a high content of triglycerides in the liver. Fatty liver occurs primarily subclinically in cows during the periparturient period and fatty liver can compromise liver function, reduce productivity and cause health problems in cows.
Currently no non-invasive method is available for quantification of fatty liver. Therefore, there is an urgent need for biomarkers for differential diagnosis and development of strategies for prevention of fatty liver. A potential subclinical biomarker can provide means to monitor and intervene in disease development at a very early stage in disease progression. The first main objective of this study is therefore to perform a characterization of the liver proteome in cows with fatty liver, and suggest potential biomarkers for fatty liver in cows.
In humans, non-alcoholic fatty liver disease (NAFLD) is estimated to affect 10-24% of the population. The NAFLD clinical spectrum ranges from abnormal retention of lipids within the hepatocytes (hepatic steatosis) to hepatic cirrhosis with liver failure. The main risk factors for NAFLD include sedentary lifestyle and poor dietary choices associated with central obesity, diabetes and hyperlipidemia. The pig, being a single stomached mammal, is considered a suitable model organism for humans. Human NAFLD may be influenced by dietary fat, whereas a typical ruminant diet contains only 2-5% fat. In addition, the cow liver has a very limited lipid secretion capacity compared to non-ruminants like rodents, swine and humans. The second main objective is therefore to develop a nutritional model of human NAFLD in the pig.
The diagnosis of fatty liver is a prerequisite for this project. Liver specimens obtained by percutaneous needle biopsy are used to assess the degree of fatty liver by clinical-chemical analysis. Liver extraction procedures applied in other studies have not been properly described and evaluated. The lack of standardization has resulted in differences in the estimated liver fat content. The third main objective is therefore to develop and evaluate a liver extraction procedure for a precise fatty liver diagnosis based on small liver biopsies.
Thus, the PhD project is divided into three subprojects with the main objectives outlined above.
These subprojects are:
- Liver Clinical-Chemical Analysis
- Liver Protein Expression in Cows with Fatty Liver (cow study)
- Effects of High Fat Feeding and Starvation on the Porcine Liver (pig study)