Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612744
Poster Visit Session III Metabolism and Transport – Friday, January 26, 2018, 4:30pm – 5:15pm, Foyer area East Wing
Georg Thieme Verlag KG Stuttgart · New York

Iso-Alpha Acids (IAA) from hops (Humulus lupulus) inhibit hepatic steatosis, inflammation and fibrosis

A Mahli
1   Friedrich-Alexander University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen
,
A Koch
1   Friedrich-Alexander University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen
,
K Freese
1   Friedrich-Alexander University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen
,
I Bergheim
2   University of Vienna, Department of Nutritional Sciences, Molecular Nutritional Science, Vienna
,
W Thasler
3   Ludwig-Maximilians-University Munich, Biobank o.b. HTCR, Department of General Visceral- and Transplantation Surgery, Munich
,
C Hellerbrand
1   Friedrich-Alexander University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

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Non-alcoholic Fatty Liver Disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome. Iso-alpha-acids (IAA), hop-derived bitter compounds in beer, have been shown to beneficially affect different components of the metabolic syndrome such as insulin resistance and dyslipidemia. However, IAA have not yet been studied in the context of chronic liver disease.

The aim of this study was to analyze the effect of IAA on the pathogenesis of NAFLD.

Methods:

IAA were applied to mice in combination with a NAFLD-inducing Western type diet (WTD). Furthermore, IAA effects on primary human hepatocytes (PHH) and hepatic stellate cells (HSC) were analyzed in vitro.

Results:

IAA significantly inhibited WTD-induced body weight-gain, glucose intolerance and hepatic steatosis. Fitting to this, IAA dose-dependently inhibited cellular lipid accumulation in PHH in vitro. Reduced expression of PPAR-gamma and key enzymes of lipid synthesis as well as increased expression of PPAR-alpha, indicative for increased lipid combustion, were identified as underlying mechanisms of reduced hepatocellular steatosis in vitro and in vivo. Analysis of hepatic HMOX1 expression showed reduced oxidative stress in IAA treated mice, which was paralleled by reduced serum transaminase levels, reduced activation of the JNK-pathway and pro-inflammatory gene expression and immune cell infiltration, as well as reduced HSC activation and profibrogenic gene expression. Fitting to this, IAA dose-dependently reduced oxidative stress and JNK-activation in steatotic PHH, inhibited HSC activation and reduced proliferation and pro-fibrogenic gene expression in already activated HSC in vitro.

Conclusion:

IAA inhibit different pathophysiological steps of disease progression in NAFLD. Together with previous studies, which demonstrated the safety of even long term application of IAA in men, our data suggest IAA as promising therapeutic agent for the prevention and treatment of (non) alcoholic (fatty) liver disease.