Scientists Elucidate the Role of Fatty Liver in Type 2 Diabetes Pathogenesis

In a review article analyzing novel data that has emerged during the past five years, scientists of the University of Tübingen, a partner in the DZD, have found that fatty liver plays a key role in the pathogenesis both of type 2 diabetes and cardiovascular disease. Previously, researchers had assumed that increasing obesity and body fat mass in the population were the main culprits responsible for the global increase in prevalence of these diseases.


For many years, Professor Dr. Norbert Stefan, holder of the Heisenberg Professorship for Clinical and Experimental Diabetology, and his research team have studied hormones that are secreted from the liver into the blood in varying levels, depending on whether the test subject suffers from nonalcoholic fatty liver disease (NAFLD) or is healthy. The researchers showed that the hormones play a direct role in the pathogenesis of type 2 diabetes and cardiovascular disease. In a review article published in the current issue of the renowned journal Nature Reviews Endocrinology, Professor Stefan and Professor Dr. Hans-Ulrich Häring, Tübingen University Hospital, presented their new concept regarding the role of specific liver hormones in the pathogenesis of these diseases.

Tübingen scientists point to the role of hepatokines 
The scientists show how fatty liver, in analogy to the expanded adipose tissue mass, alters its secretion behavior and secretes proteins – termed hepatokines – in varying quantities into the bloodstream. These proteins reach other organs where they subsequently exercise their effect. Together with colleagues at the German Institute of Human Nutrition in Potsdam-Rehbrücke (DIfE), another partner in the DZD, they described one of the most important hepatokines regulating human metabolism, the protein fetuin-A. Other important hepatokines include the sex hormone binding globulin (SHBG) and FGF-21.
Because fat mass and adipose tissue hormone levels in the blood only partially predict the risk of type 2 diabetes and cardiovascular disease, this new concept is of particular diagnostic importance. “In the future, circulating levels of hepatokines may not only serve as biomarkers to facilitate earlier diagnosis of fatty liver but may also help predict the risk of developing metabolic diseases, especially in normal to slightly overweight people,” said Professor Stefan. Within the DZD, further studies are in progress on this topic.

Original publication
Stefan N, Häring HU. The role of hepatokines in metabolism. Nat Rev Endocrinol. 2013 Mar;9(3):144-52. doi: 10.1038/nrendo.2012.258. Epub 2013 Jan 22.

Please click here to see the abstract.