Abstract
The mechanisms underlying the progression of simple steatosis to steatohepatitis are yet to be elucidated. To identify the proteins involved in the development of liver tissue inflammation, we performed comparative proteomic analysis of non-alcoholic steatohepatitis (NASH). Mice fed a methionine and choline deficient diet (MCD) developed hepatic steatosis characterized by increased free fatty acid (FFA) and triglyceride levels as well as alpha-SMA. Two-dimensional proteomic analysis revealed that the change from the normal diet to the MCD diet affected the expressions of 50 proteins. The most-pronounced changes were observed in the expression of proteins involved in Met metabolism and oxidative stress, most of which were significantly downregulated in NASH model animals. Peroxiredoxin (Prx) is the most interesting among the modulated proteins identified in this study. In particular, cross-regulated Prx1 and Prx6 are likely to participate in cellular defense against the development of hepatitis. Thus, these Prx isoforms may be a useful new marker for early stage steatohepatitis. Moreover, curcumin treatment results in alleviation of the severity of hepatic inflammation in steatohepatitis. Notably, curcumin administration in MCD-fed mice dramatically reduced CYP2E1 as well as Prx1 expression, while upregulating Prx6 expression. These findings suggest that curcumin may have a protective role against MCD fed-induced oxidative stress.
Highlights
Fatty liver disease is commonly associated with metabolic disorder or alcohol abuse and is characterized by the accumulation of fat in the liver
The groups were as follows: (1) Normal diet (ND) (n = 10): animals fed the standard diet for 12 weeks; (2) methionine and choline deficient diet (MCD) (n = 8): animals fed the MCD diet for 3 weeks (S1 Table); and (3) MCD diet supplemented with curcumin (n = 8): animals treated with MCD + curcumin diet for 3 weeks
The goal of this work was to identify differentially expressed proteins in steatohepatitis, and to characterize metabolic pathways that may explain the onset of steatohepatitis
Summary
Fatty liver disease is commonly associated with metabolic disorder or alcohol abuse and is characterized by the accumulation of fat in the liver. Non-alcoholic fatty liver disease (NAFLD) is frequently associated with elements of the metabolic syndrome, namely obesity, type 2 diabetes, and dyslipidemia. The pathophysiological picture of NAFLD ranges between simple steatosis, non-alcoholic steatohepatitis (NASH), and progressive fibrosis [1]. The mechanisms of simple steatosis progression to NASH are not yet fully understood. One proposed model for PLOS ONE | DOI:10.1371/journal.pone.0120577. One proposed model for PLOS ONE | DOI:10.1371/journal.pone.0120577 April 7, 2015
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
