GC–MS metabolic profiling reveals fructose-2,6-bisphosphate regulates branched chain amino acid metabolism in the heart during fasting

Albert Batushansky, Satoshi Matsuzaki, Maria F. Newhardt, Melinda S. West, Timothy M. Griffin, Kenneth M. Humphries

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Introduction: As an insulin sensitive tissue, the heart decreases glucose usage during fasting. This response is mediated, in part, by decreasing phosphofructokinase-2 (PFK-2) activity and levels of its product fructose-2,6-bisphosphate. However, the importance of fructose-2,6-bisphosphate in the fasting response on other metabolic pathways has not been evaluated. Objectives: The goal of this study is to determine how sustaining cardiac fructose-2,6-bisphosphate levels during fasting affects the metabolomic profile. Methods: Control and transgenic mice expressing a constitutively active form of PFK-2 (Glyco Hi ) were subjected to either 12-h fasting or regular feeding. Animals (n = 4 per group) were used for whole-heart extraction, followed by gas chromatography–mass spectrometry metabolic profiling and multivariate data analysis. Results: Principal component analysis displayed differences between Control and Glyco Hi groups under both fasting and fed conditions while a clear response to fasting was observed only for Control animals. However, pathway analysis revealed that these smaller changes in the Glyco Hi group were significantly associated with branched-chain amino acid (BCAA) metabolism (~ 40% increase in all BCAAs). Correlation network analysis demonstrated clear differences in response to fasting between Control and Glyco Hi groups amongst most parameters. Notably, fasting caused an increase in network density in the Control group from 0.12 to 0.14 while the Glyco Hi group responded oppositely (0.17–0.15). Conclusions: Elevated cardiac PFK-2 activity during fasting selectively increases BCAAs levels and decreases global changes in metabolism.

Original languageEnglish
Article number18
Issue number2
StatePublished - 1 Feb 2019
Externally publishedYes


  • Cardiac metabolism
  • Correlation network
  • GC–MS metabolomics
  • Heart pathologies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry


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