Causes and Treatment of Non-alcoholic Fatty Liver Disease (NAFLD)

Coordinators:

Michael Roden | Andreas Birkenfeld | Norbert Stefan

Excess fat in the liver not only leads to chronic disease of the organ, it also has a negative impact on metabolism and can contribute to the development of type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Europe and the USA. In Germany, about 18 million people suffer from this disease,  and about three million have non-alcoholic steatohepatitis (NASH). But why does a non-alcoholic fatty liver develop? How does it progress? Who is particularly at risk? The DZD is seeking answers to these questions in preclinical and clinical studies, among other things, in order to develop new strategies to prevent fatty liver or better treat the disease associated with type 2 diabetes. The DZD is also investigating the mechanisms of action of various drugs.

The aims of the Academy are:

  • Development and testing of new treatment strategies for NAFLD, especially in the case of  type 2 diabetes
  • Elucidation of the underlying mechanisms of liver medications
  • Identification of new targets for the prevention and treatment of metabolic liver diseases
  • Understanding the pathophysiological regulation of liver metabolism in diabetes

Diabetes subtype SIRD often develops NAFLD
Non-alcoholic fatty liver disease is also a complication of type 2 diabetes. DZD researchers have shown that patients suffering from the subtype of severe insulin-resistant diabetes (SIRD) are particularly prone to fatty liver disease.
The EMLIFA study showed that the diabetes drug empagliflozin, an SGLT-2 inhibitor, can significantly reduce liver fat levels in patients. In addition, the DZD examined the effects of the active substances empagliflozin, liraglutide and pioglitazone on liver morphology and insulin sensitivity in a NASH mouse model. Various preclinical NAFLD / NASH models for hepatic lipid and energy metabolism were also tested.

Publications

Liver fibrosis-activated transcriptional networks govern hepatocyte reprogramming and intra-hepatic communication. Cell Metabolism (2021), DOI: 10.1016/j.cmet.2021.06.005

Immunity-related GTPase induces lipophagy to prevent excess hepatic lipid accumulation. Journal of Hepatology (2020); DOI: https://doi.org/10.1016/j.jhep.2020.04.031

Epigenetic Changes in Islets of Langerhans Preceding the Onset of Diabetes. Diabetes (2020), DOI: doi.org/10.2337/db20-0204

Role of Patatin-Like Phospholipase Domain-Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes. Diabetes Care (2020), DOI: 10.2337/dc20-0329

Lipodystrophic Nonalcoholic Fatty Liver Disease Induced by Immune Checkpoint Blockade. Ann Intern Med (2020), DOI: 10.7326/L19-0635

Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial. Diabetes Care (2019), DOI: 10.2337/dc19-0641

Prof. Dr. Michael Roden, Head DZD Academy Non-alcoholic Fatty Liver Disease

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Talk at the 10th anniversary celebration of the DZD on June 24, 2019 in Berlin (in English).

Members of the Academy

Andreas Birkenfeld, IDM
Triantafyllos Chavakis, PLID
Ünal Coskun, PLID
Stephan Herzig, HMGU
Andrea Icks, DDZ
Wenke Jonas, DIfE
Stefan Kabisch, DIfE
Sabine Kahl, DDZ
Stefan Kopf, Heidelberg
Natalie Krahmer, HMGU
Thomas Laeger, DIfE
Andreas Peter, IDM
Andreas Pfeiffer, DIfE
Michael Roden, DDZ
Annette Schürmann, DIfE
Norbert Stefan, IDM
Anja Zeigerer, HMGU