Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease

Gastroenterology. 2014 Jan;146(1):46-62. doi: 10.1053/j.gastro.2013.11.001. Epub 2013 Nov 7.


Metabolic syndrome, a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease, is becoming an increasing global health concern. Insulin resistance is often associated with metabolic syndrome and also typical hepatic manifestations such as nonalcoholic fatty liver disease. Profiling of metabolic products (metabolic phenotyping or metabotyping) has provided new insights into metabolic syndrome and nonalcoholic fatty liver disease. Data from nuclear magnetic resonance spectroscopy and mass spectrometry combined with statistical modeling and top-down systems biology have allowed us to analyze and interpret metabolic signatures in terms of metabolic pathways and protein interaction networks and to identify the genomic and metagenomic determinants of metabolism. For example, metabolic phenotyping has shown that relationships between host cells and the microbiome affect development of the metabolic syndrome and fatty liver disease. We review recent developments in metabolic phenotyping and systems biology technologies and how these methodologies have provided insights into the mechanisms of metabolic syndrome and nonalcoholic fatty liver disease. We discuss emerging areas of research in this field and outline our vision for how metabolic phenotyping could be used to study metabolic syndrome and fatty liver disease.

Keywords: BCAA; FMO3; GSH; LC; MS; MSEA; Metabolic Syndrome; Metabonomics; NAFLD; NASH; NMR; Nonalcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis; RYGB; Roux-en-Y gastric bypass; SNP; TMA; TMAO; branched-chain amino acid; flavin-containing monooxygenase 3; glutathione; iMIM; integrated metabolome and interactome mapping; liquid chromatography; mGWAS; mQTL; mass spectrometry; metabolite set enrichment analysis; metabolomic genome-wide association studies; metabolomic quantitative trait locus; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; nuclear magnetic resonance; single nucleotide polymorphism; trimethylamine; trimethylamine-N-oxide.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fatty Liver / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Metabolic Syndrome / metabolism*
  • Metabolome / physiology*
  • Metabolomics / methods
  • Models, Biological
  • Non-alcoholic Fatty Liver Disease
  • Phenotype
  • Risk Factors
  • Systems Biology / methods