RT Journal Article
SR Electronic
T1 Gene Expression and Tracer-Based Metabolic Flux Analysis Reveals Tissue-Specific Metabolic Scaling <em>in vitro, ex vivo</em>, and <em>in vivo</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.02.482685
DO 10.1101/2022.03.02.482685
A1 Ngozi D. Akingbesote
A1 Brooks P. Leitner
A1 Daniel G. Jovin
A1 Reina Desrouleaux
A1 Wanling Zhu
A1 Zongyu Li
A1 Michael N. Pollak
A1 Rachel J. Perry
YR 2022
UL http://biorxiv.org/content/early/2022/03/04/2022.03.02.482685.abstract
AB Metabolic scaling, the inverse correlation of metabolic rates to body mass, has been appreciated for more than 80 years. Studies of metabolic scaling have almost exclusively been restricted to mathematical modeling of oxygen consumption. The possibility that other metabolic processes scale with body size has not been studied. To address this gap in knowledge, we employed a systems approach spanning from transcriptomics to in vitro and in vivo tracer-based flux. Gene expression in livers of five species spanning a 30,000-fold range in mass revealed differential expression of genes related to cytosolic and mitochondrial metabolic processes, in addition to detoxication of oxidative damage. This suggests that transcriptional scaling of damage control mechanisms accommodates increased oxidative metabolism in smaller species. To determine whether flux through key implicated metabolic pathways scaled, we applied stable isotope tracer methodology to study multiple cellular compartments, tissues, and species. Comparing mice and rats, we demonstrate that while scaling of metabolic fluxes is not observed in the cell-autonomous setting, it is present in liver slices and in vivo. Together, these data reveal that metabolic scaling extends beyond oxygen consumption to numerous other metabolic pathways, and is likely regulated at the level of gene expression and substrate supply.Competing Interest StatementThe authors have declared no competing interest.