Metabolite Exchange between Mammalian Organs Quantified in Pigs

Area of Science:

• Metabolomics
• Physiology
• Systems Biology

Background:

• Mammalian organs continuously exchange metabolites through circulation.
• A systems-level understanding of this metabolic shuttling process is currently lacking.
• Characterizing inter-organ metabolite flux is crucial for understanding whole-body metabolic homeostasis.

Purpose of the Study:

• To quantitatively map inter-organ metabolite exchange in mammals.
• To identify tissue-specific production and consumption of metabolites.
• To provide a comprehensive atlas of circulating metabolite dynamics.

Main Methods:

• Comparison of metabolite concentrations in arterial and draining venous blood from 11 organs in fasted pigs.
• Analysis of arterial-venous concentration differences to determine net metabolite flux.
• High-throughput metabolomic profiling to capture a wide range of metabolites.

Main Results:

• Over 90% of metabolites exhibited significant arterial-venous differences across at least one organ.
• The liver and kidneys released glucose and amino acids, primarily consumed by the intestine and pancreas.
• Unexpected organ-specific activities were identified, including preferential fatty acid utilization by the liver and citrate metabolism by the kidneys.

Conclusions:

• Mammalian organs engage in extensive and dynamic metabolite exchange, challenging previous assumptions.
• The liver and kidneys play a central role in nutrient supply and metabolic regulation.
• This study provides a foundational quantitative atlas for inter-organ metabolic communication.