The Influence of Different Fat Sources on Steatohepatitis and Fibrosis Development in the Western Diet Mouse Model of Non-alcoholic Steatohepatitis (NASH)
Authors
Drescher, Hannah K.Weiskirchen, Ralf
Fulop, Annabelle
Hopf, Carsten
de San Roman, Estibaliz Gonzalez
Huesgen, Pitter F.
de Bruin, Alain
Bongiovanni, Laura
Christ, Anette
Tolba, Rene
Trautwein, Christian
Kroy, Daniela C.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2019-06-25Keywords
Western dietanimal model and liver injury
fatty liver
fibrosis
non-alcoholic steatohepatitis
Digestive System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Lipids
Pathological Conditions, Signs and Symptoms
Physiology
Metadata
Show full item recordAbstract
Non-alcoholic steatohepatitis (NASH) is the leading cause of chronic liver injury and the third most common reason for liver transplantations in Western countries. It is unclear so far how different fat sources in Western diets (WD) influence the development of NASH. Our study investigates the impact of non-trans fat (NTF) and corn oil (Corn) as fat source in a WD mouse model of steatohepatitis on disease development and progression. C57BL/6J wildtype (WT) mice were fed "standard" WD (WD-Std), WD-NTF or WD-Corn for 24 weeks. WT animals treated with WD-NTF exhibit distinct features of the metabolic syndrome compared to WD-Std and WD-Corn. This becomes evident by a worsened insulin resistance and elevated serum ALT, cholesterol and triglyceride (TG) levels compared to WD-Corn. Animals fed WD-Corn on the contrary tend to a weakened disease progression in the described parameters. After 24 weeks feeding with WD-NTF and WD-Std, WD-Corn lead to a comparable steatohepatitis initiation by histomorphological changes and immune cell infiltration compared to WD-Std. Immune cell infiltration results in a significant increase in mRNA expression of the pro-inflammatory cytokines IL-6 and TNF-alpha, which is more pronounced in WD-NTF compared to WD-Std and WD-Corn. Interestingly the fat source has no impact on the composition of accumulating fat within liver tissue as determined by matrix-assisted laser desorption/ionization mass spectrometry imaging of multiple lipid classes. The described effects of different fat sources on the development of steatohepatitis finally resulted in variations in fibrosis development. Animals treated with WD-NTF displayed massive collagen accumulation, whereas WD-Corn even seems to protect from extracellular matrix deposition. Noteworthy, WD-Corn provokes massive histomorphological modifications in epididymal white adipose tissue (eWAT) and severe accumulation of extracellular matrix which are not apparent in WD-Std and WD-NTF treatment. Different fat sources in WD-Std contribute to strong steatohepatitis development in WT mice after 24 weeks treatment. Surprisingly, corn oil provokes histomorphological changes in eWAT tissue. Accordingly, both WD-NTF and WD-Corn appear suitable as alternative dietary treatment to replace "standard" WD-Std as a diet mouse model of steatohepatitis whereas WD-Corn leads to strong changes in eWAT morphology.Source
Front Physiol. 2019 Jun 25;10:770. doi: 10.3389/fphys.2019.00770. eCollection 2019. Link to article on publisher's site
DOI
10.3389/fphys.2019.00770Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41090PubMed ID
31293441Related Resources
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Copyright © 2019 Drescher, Weiskirchen, Fülöp, Hopf, de San Román, Huesgen, de Bruin, Bongiovanni, Christ, Tolba, Trautwein and Kroy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.3389/fphys.2019.00770
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Except where otherwise noted, this item's license is described as Copyright © 2019 Drescher, Weiskirchen, Fülöp, Hopf, de San Román, Huesgen, de Bruin, Bongiovanni, Christ, Tolba, Trautwein and Kroy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.