Marie Liebig1, Dirk Dannenberger2, Brigitte Vollmar1, Kerstin Abshagen1. 1. Rudolf-Zenker-Institute for Experimental Surgery, University Medicine Rostock, 18057 Rostock, Germany. 2. Institute of Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany.
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis. Possible reasons for the NAFLD epidemic in industrialized countries are the high intake of pro-inflammatory n-6 polyunsaturated fatty acids (n-6 PUFAs) and low consumption of healthy n-3 PUFAs. Due to their anti-inflammatory properties, n-3 PUFAs may have the potential to alleviate chronic liver disease. Herein, we examined the therapeutic effect of increased n-3 PUFA tissue levels in fat-1 transgenic mice on progressive NASH. METHODS: Disease was induced in mice by streptozotocin and high fat diet (STZ/HFD) resulting in NASH. NAFLD in 6 and 8 weeks old wild type and fat-1 transgenic STZ/HFD treated mice was analyzed. Unlike all other mammals, fat-1 transgenic mice ubiquitously express an n-3 fatty acid desaturase, which converts n-6 to n-3 PUFAs, leading to increased n-3 and decreased n-6 PUFA tissue contents. RESULTS: Liver damage, NAFLD activity score (NAS), hepatic lipid accumulation and inflammation were significantly reduced in fat-1 transgenic STZ/HFD treated mice in the early (6 weeks) but not late (8 weeks) phase of NASH. Simultaneously, mRNA expression of genes involved in fatty acid uptake and storage (Cd36 and Plin3, respectively) was significantly down-regulated in 6 week old but not 8 week old fat-1 transgenic STZ/HFD treated mice. CONCLUSIONS: Endogenously elevated n-3 PUFA levels in fat-1 transgenic mice transiently delay the onset of STZ/HFD induced NASH but failed to efficiently protect from NASH development. 2019 Hepatobiliary Surgery and Nutrition. All rights reserved.
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis. Possible reasons for the NAFLD epidemic in industrialized countries are the high intake of pro-inflammatory n-6 polyunsaturated fatty acids (n-6 PUFAs) and low consumption of healthy n-3 PUFAs. Due to their anti-inflammatory properties, n-3 PUFAs may have the potential to alleviate chronic liver disease. Herein, we examined the therapeutic effect of increased n-3 PUFA tissue levels in fat-1 transgenic mice on progressive NASH. METHODS: Disease was induced in mice by streptozotocin and high fat diet (STZ/HFD) resulting in NASH. NAFLD in 6 and 8 weeks old wild type and fat-1 transgenic STZ/HFD treated mice was analyzed. Unlike all other mammals, fat-1 transgenic mice ubiquitously express an n-3 fatty acid desaturase, which converts n-6 to n-3 PUFAs, leading to increased n-3 and decreased n-6 PUFA tissue contents. RESULTS: Liver damage, NAFLD activity score (NAS), hepatic lipid accumulation and inflammation were significantly reduced in fat-1 transgenic STZ/HFD treated mice in the early (6 weeks) but not late (8 weeks) phase of NASH. Simultaneously, mRNA expression of genes involved in fatty acid uptake and storage (Cd36 and Plin3, respectively) was significantly down-regulated in 6 week old but not 8 week old fat-1 transgenic STZ/HFD treated mice. CONCLUSIONS: Endogenously elevated n-3 PUFA levels in fat-1 transgenic mice transiently delay the onset of STZ/HFD induced NASH but failed to efficiently protect from NASH development. 2019 Hepatobiliary Surgery and Nutrition. All rights reserved.
Authors: Samer Gawrieh; Miranda C Marion; Richard Komorowski; James Wallace; Michael Charlton; Ahmed Kissebah; Carl D Langefeld; Michael Olivier Journal: Dig Dis Sci Date: 2011-12-09 Impact factor: 3.199
Authors: Charles P Najt; Subramanian Senthivinayagam; Mohammad B Aljazi; Kelly A Fader; Sandra D Olenic; Julienne R L Brock; Todd A Lydic; A Daniel Jones; Barbara P Atshaves Journal: Am J Physiol Gastrointest Liver Physiol Date: 2016-03-11 Impact factor: 4.052
Authors: Gladys M Varela; Daniel A Antwi; Ravindra Dhir; Xiaoyan Yin; Neel S Singhal; Mark J Graham; Roseanne M Crooke; Rexford S Ahima Journal: Am J Physiol Gastrointest Liver Physiol Date: 2008-07-31 Impact factor: 4.052