Metabolic flux between organs measured by arteriovenous metabolite gradients

Abstract

Mammalian organs convert dietary nutrients into circulating metabolites and share them to maintain whole-body metabolic homeostasis. While the concentrations of circulating metabolites have been frequently measured in a variety of pathophysiological conditions, the exchange flux of circulating metabolites between organs is not easily measurable due to technical difficulties. Isotope tracing is useful for measuring such fluxes for a metabolite of interest, but the shuffling of isotopic atoms between metabolites requires mathematical modeling. Arteriovenous metabolite gradient measurements can complement isotope tracing to infer organ-specific net fluxes of many metabolites simultaneously. Here, we review the historical development of arteriovenous measurements and discuss their advantages and limitations with key example studies that have revealed metabolite exchange flux between organs in diverse pathophysiological contexts.

Untargeted Metabolomics Profiling Reveals Exercise Intensity-Dependent Alterations in Thoroughbred Racehorses’ Plasma after Routine Conditioning Sessions

“…Notably, extensive documentation in human studies demonstrates the influence of both internal and external factors of the metabolome. − Moreover, the plasma metabolome provides a “snapshot” of the fluxes (i.e., uptake and release processes) of different organs. The observed relative changes in plasma metabolites induced by exercise reflect dynamic alterations and additional methods such as arteriovenous metabolite gradient measurements or isotope tracing could be employed to delve deeper into the understanding of the uptake and release processes between the circulation and other organs . Therefore, the observed alterations in metabolites should be considered as a complex interplay of multiple factors, necessitating careful interpretation and further exploration to determine their physiological implication.…”

“…The observed relative changes in plasma metabolites induced by exercise reflect dynamic alterations and additional methods such as arteriovenous metabolite gradient measurements or isotope tracing could be employed to delve deeper into the understanding of the uptake and release processes between the circulation and other organs. 54 Therefore, the observed alterations in metabolites should be considered as a complex interplay of multiple factors, necessitating careful interpretation and further exploration to determine their physiological implication. Samples collected 30 min post-exercise were analyzed; therefore, the observed metabolites’ modifications could be attributed to a combination of exercise-induced changes as well as ongoing recovery processes.…”

Plasmalogens and Octanoylcarnitine Serve as Early Warnings for Central Retinal Artery Occlusion

“…During the circulation of blood through organs, the substances it carries can enter cells to participate in metabolism, and the metabolic waste generated enters the bloodstream for removal [21]. Consequently, there can be differences in the levels of metabolites between arterial blood entering organs and venous blood exiting organs, referred to as arteriovenous metabolite differences [22][23][24]. These differences can re ect the metabolic status of organs, helping understand normal organ homeostasis and potential organ pathologies.…”

Transcriptomics and metabolomics: Challenges of studying obesity in osteoarthritis

“…As described herein, individual joint tissues and biofluids have been investigated with respect to metabolomic and transcriptomic changes associated with obesity in OA; however, interactions of joint tissues via paracrine mechanisms may also influence how tissues react and respond during OA to obesity [ 13 , 60 ]. The same can be true of how joint and systemic tissues may interact via miRNA and metabolite transfer between target tissues [ [61] , [62] , [63] , [64] , [65] ]. Thus, understanding the interactions between transcriptomes and metabolomes of local joint and systemic tissues and fluids will help to understand how obesity modifies OA and identify better therapeutics for modifying OA disease in obese individuals.…”