TRAUNER Michael, M.D.

Research Interests: Bile Acids, Lipotoxicity, Fatty Liver, Obesity

Besides their well-established roles in dietary lipid absorption and cholesterol homeostasis, emerging evidence suggests that bile acids (BA) may also play a key role as signaling molecules in the regulation of hepatic triglyceride (TG) metabolism and energy homeostasis. Therefore, hepatobiliary BA transporters, which maintain BA flux through the liver and the return of BA from the intestine to the liver via the enterohepatic circulation, as well as the key regulatory nuclear BA receptor (farnesoid X receptor, FXR) may play pivotal roles in the control of hepatic lipid homeostasis and pathogenesis of fatty liver disease.

Lipotoxicity resulting from excess of unsaturated fatty acids (FAs) may be a key event in the progression of NAFLD disease by inducing hepatocellular death, activating Kupffer cells as liver resident macrophages, impairing hepatic insulin signalling, and activation of a fibrogenic response in hepatic stellate cells that can ultimately lead to cirrhosis and hepatocellular cancer.Metabolic lipases may play a critical role in the progression of fatty liver disease by determining lipid partitioning and FA  flux and signaling from the adipose tissue to the liver.

Based on our central hypothesis that metabolic lipases play a critical role in the progression of NAFLD by determining hepatic FA flux and signaling, we will explore the consequences of altered metabolic lipase action in the pathogenesis of hepatic lipotoxicity with subsequent hepatocellular injury, inflammation, fibrosis and cancer. Moreover, we will explore the role of BAs as potential therapeutic modulators of metabolic lipases potentially counteracting hepatic lipotoxicity.

Methods & Techniques

Phenotypic and molecular characterization of transgenic mouse models for bile acid transport and signaling; knockout mouse models for metabolic lipases; mouse models for NAFLD and cholestatic disorders; cell culture; human and mouse organoids; bile acid, lipid and molecular analysis; lipase assays in isolated cells and tissues

Selected Publications

Fuchs CD, Trauner M. Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology. Nat Rev Gastroenterol Hepatol 19: 432-450, 2022

Trauner M, Fuchs CD. Novel therapeutic targets for cholestatic and fatty liver disease. Gut 71: 194-209, 2022

Trauner M, Fuchs CD, Halilbasic E, Paumgartner G. New therapeutic concepts in bile acid transport and signaling for management of cholestasis. Hepatology 65: 1393-1404, 2017

Fuchs CD, Radun R, Dixon ED, Mlitz V, Timelthaler G, Halilbasic E, Herac M, Jonker JW, Ronda OAHO, Tardelli M, Haemmerle G, Zimmermann R, Scharnagl H, Stojakovic T, Verkade HJ, Trauner M. Hepatocyte-specific deletion of adipose triglyceride lipase (adipose triglyceride lipase/patatin-like phospholipase domain containing 2) ameliorates dietary induced steatohepatitis in mice. Hepatology 75: 125-139, 2022

Zhu C, Boucheron N, Müller AC, Májek P, Claudel T, Halilbasic E, Baazim H, Lercher A, Viczenczova C, Hainberger D, Preglej T, Sandner L, Alteneder M, Gülich AF, Khan M, Hamminger P, Remetic J, Ohradanova-Repic A, Schatzlmaier P, Donner C, Fuchs CD, Stojakovic T, Scharnagl H, Sakaguchi S, Weichhart T, Bergthaler A, Stockinger H, Ellmeier W, Trauner M. 24-Norursodeoxycholic acid reshapes immunometabolism in CD8+ T cells and alleviates hepatic inflammation. J Hepatol 5: 1164-1176, 2021

Fuchs CD, Paumgartner G, Mlitz V, Kunczer V, Halilbasic E, Leditznig N, Wahlström A, Ståhlman M, Thüringer A, Kashofer K, Stojakovic T, Marschall HU, Trauner M. Colesevelam attenuates cholestatic liver and bile duct injury in Mdr2-/-mice by modulating composition, signalling and excretion of faecal bile acids. Gut ;67: 1683-1691, 2018

Bruschi FV, Claudel T, Tardelli M, Caligiuri A, Stulnig TM, Marra F, Trauner M. The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells. Hepatology 65: 1875‐1890, 2017

Baghdasaryan A, Fuchs CD, Österreicher CH, Lemberger UJ, Halilbasic E, Påhlman I, Graffner H, Krones E, Fickert P, Wahlström A, Ståhlman M, Paumgartner G, Marschall HU, Trauner M. Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis. J Hepatol 64: 674‐681, 2016

Jha P, Claudel T, Baghdasaryan A, Mueller M, Halilbasic E, Das SK, Lass A, Zimmermann R, Zechner R, Hoefler G, Trauner M. Role of adipose triglyceride lipase (PNPLA2) in protection from hepatic inflammation in mouse models of steatohepatitis and endotoxemia. Hepatology 59: 858‐869, 2014

Fuchs CD, Claudel T, Kumari P, Haemmerle G, Pollheimer MJ, Stojakovic T, Scharnagl H, Halilbasic E, Gumhold J, Silbert D, Koefeler H, Trauner M. Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice. Hepatology 56: 270-280, 2012

Moustafa T, Fickert P, Magnes C, Guelly C, Thueringer A, Frank S, Kratky D, Sattler W, Reicher H, Sinner F, Gumhold J, Silbert D, Fauler G, Höfler G, Lass A, Zechner R, Trauner M. Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury. Gastroenterology 142: 140-151, 2012