Hyperpolarized [U‑2H, 2-13C]Fructose Distinguishes Direct Hepatic Gluconeogenesis Through Fructose-1-Phosphate Production in Fed and Fasted States

TL;DR

This study uses a special type of fructose to track how the liver processes it in fed and fasted states, helping understand liver metabolism better.

Contribution

The study introduces a new method using hyperpolarized [U-2H, 2-13C]fructose to distinguish hepatic gluconeogenesis in vivo.

Findings

Hyperpolarized [U-2H, 2-13C]fructose spectroscopy can distinguish direct hepatic gluconeogenesis.

The method was tested in mice under fed and fasted conditions.

This approach provides a foundational methodology for assessing hepatic metabolism in vivo.

Abstract

Hepatic fructose
utilization depends on ketohexokinase mediated
phosphorylation to generate fructose-1-phosphate and commit fructose
carbons to additional metabolic steps. Since dysregulated fructose
metabolism has been directly connected to the onset and progression
of liver disease and cancer, there is considerable interest in identifying
the contributions of fructose carbons in bioenergetic pathways. An
essential technology for assessing fructose utilization has been the
application of isotopically labeled fructose and magnetic resonance
with the development of 13C hyperpolarized imaging with
[2-13C]­fructose allowing for in vivo assessments.
While hyperpolarized imaging of [2-13C]­fructose has achieved
remarkable success in the detection of cancer metabolism, this approach
has yet to be utilized to assess fed and fasted states in healthy
livers. By challenging mice with a 6 h fast, we demonstrate that hyperpolarized
[U-2H, 2-13C]­fructose in vivo spectroscopy can clearly distinguish direct hepatic gluconeogenesis.
Comprehensively, this work aims to establish a foundational methodology
for the assessment of hepatic metabolism in vivo.

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