title: High-Throughput Tissue Bioenergetics Analysis Reveals Identical Metabolic Allometric Scaling for Teleost Hearts and Whole Organisms.
abstract: Organismal metabolic rate, a fundamental metric in biology, demonstrates an allometric scaling relationship with body size. Fractal-like vascular distribution networks of biological systems are proposed to underlie metabolic rate allometric scaling laws from individual organisms to cells, mitochondria, and enzymes. Tissue-specific metabolic scaling is notably absent from this paradigm. In the current study, metabolic scaling relationships of hearts and brains with body size were examined by improving on a high-throughput whole-organ oxygen consumption rate (OCR) analysis method in five biomedically and environmentally relevant teleost model species. Tissue-specific metabolic scaling was compared with organismal routine metabolism (RMO2), which was measured using whole organismal respirometry. Basal heart OCR and organismal RMO2 scaled identically with body mass in a species-specific fashion across all five species tested. However, organismal maximum metabolic rates (MMO2) and pharmacologically-induced maximum cardiac metabolic rates in zebrafish Danio rerio did not show a similar relationship with body mass. Brain metabolic rates did not scale with body size. The identical allometric scaling of heart and organismal metabolic rates with body size suggests that hearts, the power generator of an organism's vascular distribution network, might be crucial in determining teleost metabolic rate scaling under routine conditions. Furthermore, these findings indicate the possibility of measuring heart OCR utilizing the high-throughput approach presented here as a proxy for organismal metabolic rate-a useful metric in characterizing organismal fitness. In addition to heart and brain OCR, the current approach was also used to measure whole liver OCR, partition cardiac mitochondrial bioenergetic parameters using pharmacological agents, and estimate heart and brain glycolytic rates. This high-throughput whole-organ bioenergetic analysis method has important applications in toxicology, evolutionary physiology, and biomedical sciences, particularly in the context of investigating pathogenesis of mitochondrial diseases.
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina, United States of America.
authors.forename: Nishad
authors.initials: N
authors.lastname: Jayasundara
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina, United States of America.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Kozal
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina, United States of America.
authors.forename: Mariah C
authors.initials: MC
authors.lastname: Arnold
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Sherine S L
authors.initials: SS
authors.lastname: Chan
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina, United States of America.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Di Giulio
mesh_terms: D000818:Animals; D049628:Body Size; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism; D005399:Fishes / Q000145:classification / Q000378:metabolism*; D017709:Fractals; D057166:High-Throughput Screening Assays; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010101:Oxygen Consumption; D015027:Zebrafish / Q000378:metabolism