The primary research goal of the Chair of Nutritional Biochemistry is to develop mechanistic insights into the relationships between nutrition and health, thereby contributing to the elucidation of fundamental biochemical and physiological processes and their nutrition-dependent regulation.
- Dietary lipids and their role in the pathogenesis of fatty liver diseaseHide
While saturated fatty acids and cholesterol as an animal lipid are generally considered harmful to health at elevated consumption levels, unsaturated fatty acids are regarded as potentially "good fats". The current general dietary recommendations of the German Nutrition Society specify that saturated fatty acids should be replaced by unsaturated fatty acids.
Our previous research demonstrated that the combination of soybean oil-based high fat diets, which are rich in omega-6-poly-unsaturated fatty acids, and dietary cholesterol initiated the pathogenesis of steatohepatitis (NASH) with excessive lipid accumulation, hepatocyte death and inflammation, whereas lard-based high fat diets, which consists mainly of saturated fatty acids, and dietary cholesterol lead to a fatty liver without severe inflammation in rodents.
Our current research investigates the role of dietary lipids in patho-biochemical and patho-physiological processes in the liver and other organs. We focus on the molecular mechanisms, how the fatty acid quality (saturated, mono-unsaturated, omega-3-poly-unsaturated and omega-6-poly-unsaturated) alone and in combination with cholesterol influence hepatocyte metabolism and lead to cellular damage.
- Prostaglandins and their role in the severity of fatty liver diseaseHide
A diet-induced expansion of the white adipose tissue is associated with the development of insulin resistance as well as low-grade chronic inflammation. Inflammatory mediators from the adipose tissue in combination with dietary components from the gut reach the liver and activate Kupffer cells, the resident liver macrophages. As a consequence, macrophages initiate an inflammatory response that involves secretion of immune cell recruiting chemokines, pro-inflammatory cytokines and prostanoids such as prostaglandin E2 (PGE2).
The aim of the project is to elucidate the impact of the bioactive lipid PGE2 in the development of insulin resistance, hepatic steatosis and inflammation in diet-induced NASH. This includes intervention studies in transgenic mice with tissue-specific deletion of prostaglandin E-generating enzymes as well as in vitro studies with primary cells isolated from wildtype and transgenic mice or cell lines.
- Regulation of macrophage activity by dietary metabolitesHide
Macrophages are phagocytosing cells of the immune system. Both in acute inflammatory reactions such as infections and in chronic inflammatory reactions, macrophage precursor cells (monocytes) migrate into affected tissues and influence their metabolism. Overweight or obese patients often suffer from such a low-grade chronic inflammation in addition to dyslipidemia, insulin resistance with an ensuing hyperinsulinemia and a mild endotoxinemia that result from an impaired intestinal barrier function. Macrophages play a central role in this setting and are exposed to a mixture of potential modulators of an inflammatory response. This includes fatty acids released from the insulin resistant adipocytes, elevated level insulin produced to compensate insulin resistance as well as bioactive lipids such as prostaglandin E2 (PGE2), which are released from activated macrophages.
In this project we investigate the interplay between these nutrition-related parameters on the macrophage activation and the extent of the inflammatory response.