Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats
Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertens...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3308 |
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| author | Carla Cremonese Robert Schierwagen Frank Erhard Uschner Sandra Torres Olaf Tyc Cristina Ortiz Martin Schulz Alexander Queck Glen Kristiansen Michael Bader Tilman Sauerbruch Ralf Weiskirchen Thomas Walther Jonel Trebicka Sabine Klein |
| author_facet | Carla Cremonese Robert Schierwagen Frank Erhard Uschner Sandra Torres Olaf Tyc Cristina Ortiz Martin Schulz Alexander Queck Glen Kristiansen Michael Bader Tilman Sauerbruch Ralf Weiskirchen Thomas Walther Jonel Trebicka Sabine Klein |
| author_sort | Carla Cremonese |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. 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. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this 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. |
| first_indexed | 2024-03-10T19:59:04Z |
| format | Article |
| id | doaj.art-194818274e234b18a88ab51e742406f4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:59:04Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-194818274e234b18a88ab51e742406f42023-11-19T23:41:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-01219330810.3390/ijms21093308Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 RatsCarla Cremonese0Robert Schierwagen1Frank Erhard Uschner2Sandra Torres3Olaf Tyc4Cristina Ortiz5Martin Schulz6Alexander Queck7Glen Kristiansen8Michael Bader9Tilman Sauerbruch10Ralf Weiskirchen11Thomas Walther12Jonel Trebicka13Sabine Klein14Department of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyInstitute for Pathology, University of Bonn, 53127 Bonn, GermanyMax Delbrück Center for Molecular Medicine, 13092 Berlin, GermanyDepartment of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, GermanyInstitute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, 52074 Aachen, GermanyDepartment of Pharmacology and Therapeutics, University College Cork, T12 YN60 Cork, IrelandDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyDepartment of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, GermanyNon-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. 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. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this 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.https://www.mdpi.com/1422-0067/21/9/3308ADGRE1EMR1F4/80immunityliver fibrosismacrophage |
| spellingShingle | Carla Cremonese Robert Schierwagen Frank Erhard Uschner Sandra Torres Olaf Tyc Cristina Ortiz Martin Schulz Alexander Queck Glen Kristiansen Michael Bader Tilman Sauerbruch Ralf Weiskirchen Thomas Walther Jonel Trebicka Sabine Klein Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats International Journal of Molecular Sciences ADGRE1 EMR1 F4/80 immunity liver fibrosis macrophage |
| title | Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats |
| title_full | Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats |
| title_fullStr | Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats |
| title_full_unstemmed | Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats |
| title_short | Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats |
| title_sort | short term western diet aggravates non alcoholic fatty liver disease nafld with portal hypertension in tgr mren2 27 rats |
| topic | ADGRE1 EMR1 F4/80 immunity liver fibrosis macrophage |
| url | https://www.mdpi.com/1422-0067/21/9/3308 |
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