Molecular Genetics

Nutritional factors affecting non-alcoholic steatohepatitis (NASH)

Non–alcoholic steatohepatitis (NASH) is the hepatic event of the metabolic syndrome and is characterized by steatosis (fat accumulation) and inflammation. Whereas steatosis is harmless, the inflammatory component can lead to irreversible liver damage. However, the mechanisms by which inflammation is triggered are unknown. Our aims are to identify the molecular mechanisms that trigger inflammation in NASH and related metabolic diseases, to establish innovative non-invasive markers for hepatic inflammation and to identify novel treatment options for hepatic inflammation and related diseases.

Our experiments span from basic to translational science and include both mouse and human studies.The results are expected to influence a wide area of research related to metabolic syndrome as well as fields with similar mechanisms. As such, knowledge gained in this project has enormous market potential and that substantial commercial exploitation is expected.

In Maastricht, we collaborate mainly with prof. W. Buurman, P. Lindsey PhD, J. Plat PhD and prof. A. Bast. We also have a strong collaboration with clinicians specialized in liver disease (prof. S. Olde Damink, prof. K. Dejong and G. Koek PhD). A longstanding collaboration exists with prof. M. Hofker (Groningen), prof. D. Lütjohann (Bonn, Germany), prof. E. Latz (Bonn, Germany) and C.J. Binder PhD (Vienna, Austria).

Publications (selection)

Bieghs V, Hendrikx T, van Gorp PJ, Verheyen F, Guichot YD, Walenbergh SM, Jeurissen ML, Gijbels M, Rensen SS, Bast A, Plat J, Kalhan SC, Koek GH, Leitersdorf E, Hofker MH, Lütjohann D, Shiri-Sverdlov R. The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice. Gastroenterology. 2013 Jan;144(1):167-178.e1

Bieghs V, van Gorp PJ, Walenbergh SM, Gijbels MJ, Verheyen F, Buurman WA, Briles DE, Hofker MH, Binder CJ, Shiri-Sverdlov R. Specific immunization strategies against oxidized low-density lipoprotein: a novel way to reduce nonalcoholic steatohepatitis in mice. Hepatology. 2012 Sep;56(3):894-903

Bieghs V, Wouters K, van Gorp PJ, Gijbels MJ, de Winther MP, Binder CJ, Lütjohann D, Febbraio M, Moore KJ, van Bilsen M, Hofker MH, Shiri-Sverdlov R. Role of scavenger receptor A and CD36 in diet-induced nonalcoholic steatohepatitis in hyperlipidemic mice. Gastroenterology. 2010 Jun;138(7):2477-86, 2486.e1-3

Hendrikx T, Jeurissen ML, Bieghs V, Walenbergh SM, van Gorp PJ, Verheyen F, Houben T, Guichot YD, Gijbels MJ, Leitersdorf E, Hofker MH, Lütjohann D, Shiri-Sverdlov R. Hematopoietic overexpression of Cyp27a1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr(-/-) mice. Journal of Hepatology (2015), Feb;62(2):430-6

Hendrikx T, Watzenböck ML, Walenbergh SM, Amir S, Gruber S, Kozma MO, Grabsch HI, Koek GH, Pierik MJ, Staufer K, Trauner M, Kalhan SC, Jonkers D, Hofker MH, Binder CJ, Shiri-Sverdlov R. Low levels of IgM antibodies recognizing oxidation-specific epitopes are associated with human non-alcoholic fatty liver disease. BMC Medicine (2016), 22;14(1):107

Houben T, Brandsma E, Walenbergh SM, Hofker MH, Shiri-Sverdlov R. Oxidized LDL at the crossroads of immunity in non-alcoholic steatohepatitis. Biochimica et Biophysica Acta. - Molecular and Cell Biology of Lipids (2016), pii: S1388-1981(16)30202-5

Walenbergh SM, Houben T, Hendrikx T, Jeurissen ML, van Gorp PJ, Vreugdenhil AC, Adriaanse MP, Buurman WA, Hofker MH, Mosca A, Lindsey PJ, Alisi A, Liccardo D, Panera N, Koek GH, Nobili V, Shiri-Sverdlov R. Plasma cathepsin D levels: a novel tool to predict pediatric hepatic inflammation. American Journal of Gastroenterology (2015), Mar;110(3):462-70

Walenbergh SM, Koek GH, Bieghs V, Shiri-Sverdlov R. Non-alcoholic steatohepatitis: the role of oxidized low-density lipoproteins. J Hepatol. 2013 Apr;58(4):801-10

Wouters K, van Gorp PJ, Bieghs V, Gijbels MJ, Duimel H, Lütjohann D, Kerksiek A, van Kruchten R, Maeda N, Staels B, van Bilsen M, Hofker MH and Shiri-Sverdlov R. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis. Hepatology. 2008 Aug;48(2):474-86

Team leader

Prof. Ronit Shiri-Sverdlov, PhD

Research group

1 technician, 5 PhD students