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Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model
Author(s) -
Han JianHua,
Dzierlenga Anika L.,
Lu Zhengqiang,
Billheimer Dean D.,
Torabzadeh Elmira,
Lake April D.,
Li Hui,
Novak Petr,
Shipkova Petia,
Aranibar Nelly,
Robertson Donald,
Reily Michael D.,
LehmanMcKeeman Lois D.,
Cherrington Nathan J.
Publication year - 2017
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21855
Subject(s) - metabolome , metabolomics , nonalcoholic fatty liver disease , metabolite , methionine , choline , nonalcoholic steatohepatitis , biology , cholic acid , biochemistry , fatty liver , medicine , amino acid , disease , bioinformatics , bile acid
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.