TY  - JOUR
A1  - Cremonese, Carla-Luisa Elsa
A1  - Schierwagen, Robert
A1  - Uschner, Frank Erhard
A1  - Torres Núñez, Sandra
A1  - Tyc, Olaf
A1  - Ortiz, Cristina
A1  - Schulz, Martin
A1  - Queck, Alexander David Roger
A1  - Kristiansen, Glen
A1  - Bader, Michael
A1  - Sauerbruch, Tilman
A1  - Weiskirchen, Ralf
A1  - Walther, Thomas
A1  - Trebicka, Jonel
A1  - Klein, Sabine
T1  - Short-term western diet aggravates non-alcoholic fatty liver disease (NAFLD) with portal hypertension in TGR(mREN2)27 rats
T2  - International journal of molecular sciences
N2  - Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially,thedevelopmentoffibrosisandportalhypertensioninNAFLDpatientsrequirestreatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. Asexpected,WDinducedobesityandliverfibrosisasconfirmedbySiriusRedandOilRed O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increasedduringfeedingofWD,indicatinginfiltrationofmacrophagesintotheliver,eventhoughthis increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.
KW  - ADGRE1
KW  - EMR1
KW  - F4/80
KW  - immunity
KW  - liver fibrosis
KW  - macrophage
KW  - NAFLD
KW  - portal hypertension
KW  - TGR(mREN2)27
KW  - Western diet
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55326
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-553267
SN  - 1422-0067
SN  - 1661-6596
N1  - This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
VL  - 21
IS  - 9, art. 3308
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel
ER  -