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Medical Forum / Diseases and Disorders / Hepatitis / February 2007Iron in steatohepatitis
The remnants of destroyed red blood cells leads to nonalcoholic steatohepatitis. <<snip>> These results indicate that the engulfment of PS-externalized, apoptotic signal-positive, erythrocytes by hepatic macrophages may lead to the deposition of iron derived from hemoglobin in the liver and be involved in the pathogenesis of steatohepatitis. <<snip>> Am J Pathol. 2007 Mar;170(3):967-80.Erythrophagocytosis by liver macrophages (kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: implications for the pathogenesis of human nonalcoholic steatohepatitis.Otogawa K, Kinoshita K, Fujii H, Sakabe M, Shiga R, Nakatani K, Ikeda K, Nakajima Y, Ikura Y, Ueda M, Arakawa T, Hato F, Kawada N. Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno, Osaka 545-8585, Japan. kawadanori@med.osaka-cu.ac.jp. Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease, the pathogenesis of which has not been fully elucidated. Here, we report a molecular aspect of this disease elucidated using rabbits fed a cholesterol-rich high-fat diet and exhibiting insulin resistance. The liver in this model showed steatohepatitis with fibrosis and high mRNA expression for some cytokines, heme oxygenase-1, transforming growth factor-beta1, and collagen alpha1(I). Erythrocytes isolated from the model showed marked fragility and the externalization of phosphatidylserine (PS) on the outer leaflet of the membrane and were frequently engulfed by Kupffer cells/macrophages in the hepatic sinusoids. Expression of milk fat globule-epidermal growth factor (EGF)-factor 8, a PS-binding protein, was augmented in the liver. In culture, RAW 264.7 cells engulfed erythrocytes oxidized by tert-butyl hydroperoxide, a process that was inhibited by anti-milk fat globule- EGF-factor 8 antibody. In addition, PS-positive erythrocytes appeared entrapped in the model liver in ex vivo perfusion experiments. Finally, in specimens from NASH patients, the aggregation of erythrocytes in inflammatory hepatic sinusoids was notable. These results indicate that the engulfment of PS-externalized, apoptotic signal-positive, erythrocytes by hepatic macrophages may lead to the deposition of iron derived from hemoglobin in the liver and be involved in the pathogenesis of steatohepatitis. PMID: 17322381 [PubMed - in process] Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > The remnants of destroyed red blood cells leads to nonalcoholic > steatohepatitis. [quoted text clipped - 49 lines] > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk Research . Long term highly saturated fat diet does not induce NASH in Wistar rats Caroline Romestaing1 , Marie-Astrid Piquet2 , Elodie Bedu1 , Vincent Rouleau2 , Marianne Dautresme2 , Isabelle Hourmand- Ollivier2 , Céline Filippi3 , Claude Duchamp1 and Brigitte Sibille1 1Laboratoire de Physiologie Intégrative, Cellulaire et Moléculaire, CNRS, Université Lyon 1, F-69622 France 2Imagerie Fonctionnelle et Métabolique en Oncologie, EA 3916, Département de Nutrition et d'hépatogastroentérologie, CHU Côte de nacre, Caen, F-14033 France 3Department of Hepatology, Chancellor's Building, 49 Little France Crescent, Edinburgh, UK Nutrition & Metabolism 2007, 4:4 doi:10.1186/1743-7075-4-4 Published 21 February 2007 Abstract Background Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25-28% vs standard). Conclusion Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk |
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