A Low Iron Diet Protects from Steatohepatitis in a Mouse Model
| Autor: | Donald A. McClain, Robert C. Cooksey, Ielizaveta Bychkova, Sandy Sink, Felipe Lorenzo, Kylie Kavanagh, Herbert L. Bonkovsky, Manish S. Bharadwaj, Soh-Hyun Lee, Shalini Jain, Nuwan T. Meegalla, Alexandria Harrison, Lipika Salaye, George L. Donati, Ashley T. Davis, Katherine Turnbull, Alexander J. Kovalic |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male endocrine system diseases chemistry.chemical_compound 0302 clinical medicine Non-alcoholic Fatty Liver Disease Nutrition and Dietetics biology Fatty liver Hep G2 Cells Iron Deficiencies 3. Good health Liver Disease Progression 030211 gastroenterology & hepatology lcsh:Nutrition. Foods and food supply Iron Dietary Signal Transduction medicine.medical_specialty Iron Adipokine lcsh:TX341-641 Fructose Diet High-Fat digestive system Article metabolic syndrome 03 medical and health sciences Insulin resistance Internal medicine NAFLD medicine Animals Humans Triglyceride business.industry Type 2 Diabetes Mellitus nutritional and metabolic diseases Transforming growth factor beta medicine.disease Animal Feed digestive system diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology chemistry Gene Expression Regulation biology.protein Metabolic syndrome Steatohepatitis RNA-seq business Food Science |
| Zdroj: | Nutrients Volume 11 Issue 9 Nutrients, Vol 11, Iss 9, p 2172 (2019) |
| ISSN: | 2072-6643 |
| Popis: | High tissue iron levels are a risk factor for multiple chronic diseases including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). To investigate causal relationships and underlying mechanisms, we used an established NAFLD model&mdash mice fed a high fat diet with supplemental fructose in the water (&ldquo fast food&rdquo FF). Iron did not affect excess hepatic triglyceride accumulation in the mice on FF, and FF did not affect iron accumulation compared to normal chow. Mice on low iron are protected from worsening of markers for non-alcoholic steatohepatitis (NASH), including serum transaminases and fibrotic gene transcript levels. These occurred prior to the onset of significant insulin resistance or changes in adipokines. Transcriptome sequencing revealed the major effects of iron to be on signaling by the transforming growth factor beta (TGF-&beta ) pathway, a known mechanistic factor in NASH. High iron increased fibrotic gene expression in vitro, demonstrating that the effect of dietary iron on NASH is direct. Conclusion: A lower tissue iron level prevents accelerated progression of NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the disease. |
| Databáze: | OpenAIRE |
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