Umbreen Ahmed1, Trevor G Redgrave, Phillip S Oates. 1. Physiology M311, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Nedlands, Western Australia, Australia.
Abstract
BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression. METHODS: Male Sprague-Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks. RESULTS: Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups. CONCLUSIONS: Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.
BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression. METHODS: Male Sprague-Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks. RESULTS:Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups. CONCLUSIONS: Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.
Authors: Janina A Krumbeck; María X Maldonado-Gomez; Inés Martínez; Steven A Frese; Thomas E Burkey; Karuna Rasineni; Amanda E Ramer-Tait; Edward N Harris; Robert W Hutkins; Jens Walter Journal: Appl Environ Microbiol Date: 2015-01-23 Impact factor: 4.792
Authors: Priya Handa; Bryan D Maliken; James E Nelson; Vicki Morgan-Stevenson; Donald J Messner; Barjinderjit K Dhillon; Heather M Klintworth; Mary Beauchamp; Matthew M Yeh; Clinton T Elfers; Christian L Roth; Kris V Kowdley Journal: Hepatology Date: 2014-05-27 Impact factor: 17.425
Authors: Almudena Lomba; Fermín I Milagro; Diego F García-Díaz; Amelia Marti; Javier Campión; J Alfredo Martínez Journal: Lipids Health Dis Date: 2010-06-09 Impact factor: 3.876
Authors: Irene P Tzanetakou; Ilias P Doulamis; Laskarina-Maria Korou; George Agrogiannis; Ioannis S Vlachos; Alkisti Pantopoulou; Dimitri P Mikhailidis; Efstratios Patsouris; Ioannis Vlachos; Despina N Perrea Journal: Open Cardiovasc Med J Date: 2012-08-10