Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes

Alfred K. Ramirez, Matthew D. Lynes, Farnaz Shamsi, Ruidan Xue, Yu Hua Tseng, C. Ronald Kahn, Simon Kasif, Jonathan M. Dreyfuss

Research output: Contribution to journalArticlepeer-review

Abstract

White adipocytes are specialized for energy storage, whereas brown adipocytes are specialized for energy expenditure. Explicating this difference can help identify therapeutic targets for obesity. A common tool to assess metabolic differences between such cells is the Seahorse Extracellular Flux (XF) Analyzer, which measures oxygen consumption and media acidification in the presence of different substrates and perturbagens. Here, we integrate the Analyzer's metabolic profile from human white and brown adipocytes with a genome-scale metabolic model to predict flux differences across the metabolic map. Predictions matched experimental data for the metabolite 4-aminobutyrate, the protein ABAT, and the fluxes for glucose, glutamine, and palmitate. We also uncovered a difference in how adipocytes dispose of nitrogenous waste, with brown adipocytes secreting less ammonia and more urea than white adipocytes. Thus, the method and software we developed allow for broader metabolic phenotyping and provide a distinct approach to uncovering metabolic differences. Ramirez et al. integrate extracellular flux measurements with a human metabolic model to infer flux differences between brown (energy-burning) and white (energy-storing) adipocytes. Differences are experimentally validated. Brown adipocytes dispose of nitrogenous waste differently than white adipocytes. This method can be applied to any tissue/cell assayed with extracellular analyzers.

Original languageEnglish (US)
Pages (from-to)3040-3048
Number of pages9
JournalCell Reports
Volume21
Issue number11
DOIs
StatePublished - Dec 12 2017

Keywords

  • brown adipose tissue
  • extracellular flux analysis
  • flux balance analysis
  • metabolic flux analysis
  • white adipose tissue

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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