Z Gastroenterol 2018; 56(01): E2-E89
DOI: 10.1055/s-0037-1612742
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

Gender specific differences in Western-type diet induced steatohepatitis in mice

J Sommer
1   Friedrich-Alexander University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen
,
C Hellerbrand
1   Friedrich-Alexander University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen
2   Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2018 (online)

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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and factors driving progression to non-alcoholic steatohepatitis (NASH) are poorly understood. NASH is two to three times more common in men than women until after the age of 60, after which the prevalence is higher in women. In animal models, there is a lack of consensus as to the role of gender on the development of NAFLD.

The aim of this study was to develop a mouse model to elicit gender differences in the development and progression of NAFLD.

Methods and Results:

Starting 8 weeks after birth, male and female C57Bl/6 mice (littermates) were fed with a Western-type diet (WTD) containing 38% fat, 30% sucrose and 0.2% cholesterol for 19 weeks. Controls were fed with standard chow. WTD-induced weight gain was significantly higher in male than in female mice (male: 138 ± 21%, female: 119 ± 19%. Furthermore, only WTD-fed male but not female mice showed pathological glucose tolerance. In contrast, liver/body weight ratio and hepatic triglyceride content did not differ between sexes. However, female mice showed significantly higher hepatic CD36 and fatty acid synthase (FASN) expression in both feeding states. Furthermore, female mice had significantly higher hepatic HMG-CoA reductase (HMGCR) and ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression levels, and fitting to, significantly higher hepatic cholesterol as well as primary and secondary bile acids levels. Also, oxidative stress and pro-inflammatory gene expression were higher in WTD-fed female mice. In contrast, WTD-induced pro-fibrogenic gene expression did not differ between genders.

Conclusion:

Our study reveals significant gender specific differences in diverse facets of the pathology of NAFLD with most pronounced effects in (hepatic) lipid and cholesterol metabolisms. Future studies are needed to verify these mechanisms in men. Thereby, sex-specific and thus more effective clinical therapies to prevent liver disease development and its progression can be performed in the future.