Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model

Jian Hua Han, Anika L. Dzierlenga, Zhengqiang Lu, David D Billheimer, Elmira Torabzadeh, April D. Lake, Hui Li, Petr Novak, Petia Shipkova, Nelly Aranibar, Donald Robertson, Michael D. Reily, Lois D. Lehman-McKeeman, Nathan J Cherrington

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1069-1076
Number of pages8
JournalObesity
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2017

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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    Han, J. H., Dzierlenga, A. L., Lu, Z., Billheimer, D. D., Torabzadeh, E., Lake, A. D., Li, H., Novak, P., Shipkova, P., Aranibar, N., Robertson, D., Reily, M. D., Lehman-McKeeman, L. D., & Cherrington, N. J. (2017). Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model. Obesity, 25(6), 1069-1076. https://doi.org/10.1002/oby.21855