The intestine is a major contributor to circulating succinate in mice.

Journal Article (Journal Article)

The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra- and extracellular metabolic signals regulating pleiotropic biological processes. Despite the importance of circulating TCA cycle metabolites as signaling molecules, the source of circulating TCA cycle intermediates remains uncertain. We observe that in mice, the concentration of TCA cycle intermediates in the portal blood exceeds that in tail blood indicating that the gut is a major contributor to circulating TCA cycle metabolites. With a focus on succinate as a representative of a TCA cycle intermediate with signaling activities and using a combination of gut microbiota depletion mouse models and isotopomer tracing, we demonstrate that intestinal microbiota is not a major contributor to circulating succinate. Moreover, we demonstrate that endogenous succinate production is markedly higher than intestinal succinate absorption in normal physiological conditions. Altogether, these results indicate that endogenous succinate production within the intestinal tissue is a major physiological source of circulating succinate. These results provide a foundation for an investigation into the role of the intestine in regulating circulating TCA cycle metabolites and their potential signaling effects on health and disease.

Full Text

Duke Authors

Cited Authors

  • Tong, W; Hannou, SA; Wang, Y; Astapova, I; Sargsyan, A; Monn, R; Thiriveedi, V; Li, D; McCann, JR; Rawls, JF; Roper, J; Zhang, G-F; Herman, MA

Published Date

  • October 2022

Published In

Volume / Issue

  • 36 / 10

Start / End Page

  • e22546 -

PubMed ID

  • 36106538

Pubmed Central ID

  • PMC9523828

Electronic International Standard Serial Number (EISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.202200135RR


  • eng

Conference Location

  • United States