TY - JOUR
T1 - Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model
AU - Han, Jian Hua
AU - Dzierlenga, Anika L.
AU - Lu, Zhengqiang
AU - Billheimer, Dean D.
AU - Torabzadeh, Elmira
AU - Lake, April D.
AU - Li, Hui
AU - Novak, Petr
AU - Shipkova, Petia
AU - Aranibar, Nelly
AU - Robertson, Donald
AU - Reily, Michael D.
AU - Lehman-McKeeman, Lois D.
AU - Cherrington, Nathan J.
N1 - Publisher Copyright:
© 2017 The Obesity Society
PY - 2017/6
Y1 - 2017/6
N2 - Objective: Characteristic pathological changes define the progression of steatosis to nonalcoholic steatohepatitis (NASH) and are correlated to metabolic pathways. A common rodent model of NASH is the methionine and choline deficient (MCD) diet. The objective of this study was to perform full metabolomic analyses on liver samples to determine which pathways are altered most pronouncedly in this condition in humans, and to compare these changes to rodent models of nonalcoholic fatty liver disease (NAFLD). Methods: A principal component analysis for all 91 metabolites measured indicated that metabolome perturbation is greater and less varied for humans than for rodents. Results: Metabolome changes in human and rat NAFLD were greatest for the amino acid and bile acid metabolite families (e.g., asparagine, citrulline, gamma-aminobutyric acid, lysine); although, in many cases, the trends were reversed when compared between species (cholic acid, betaine). Conclusions: Overall, these results indicate that metabolites of specific pathways may be useful biomarkers for NASH progression, although these markers may not correspond to rodent NASH models. The MCD model may be useful when studying certain end points of NASH; however, the metabolomics results indicate important differences between humans and rodents in the biochemical pathogenesis of the disease.
AB - Objective: Characteristic pathological changes define the progression of steatosis to nonalcoholic steatohepatitis (NASH) and are correlated to metabolic pathways. A common rodent model of NASH is the methionine and choline deficient (MCD) diet. The objective of this study was to perform full metabolomic analyses on liver samples to determine which pathways are altered most pronouncedly in this condition in humans, and to compare these changes to rodent models of nonalcoholic fatty liver disease (NAFLD). Methods: A principal component analysis for all 91 metabolites measured indicated that metabolome perturbation is greater and less varied for humans than for rodents. Results: Metabolome changes in human and rat NAFLD were greatest for the amino acid and bile acid metabolite families (e.g., asparagine, citrulline, gamma-aminobutyric acid, lysine); although, in many cases, the trends were reversed when compared between species (cholic acid, betaine). Conclusions: Overall, these results indicate that metabolites of specific pathways may be useful biomarkers for NASH progression, although these markers may not correspond to rodent NASH models. The MCD model may be useful when studying certain end points of NASH; however, the metabolomics results indicate important differences between humans and rodents in the biochemical pathogenesis of the disease.
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U2 - 10.1002/oby.21855
DO - 10.1002/oby.21855
M3 - Article
C2 - 28452429
AN - SCOPUS:85018353953
SN - 1930-7381
VL - 25
SP - 1069
EP - 1076
JO - Obesity
JF - Obesity
IS - 6
ER -