Parental cardiorespiratory fitness influences early life energetics and metabolic health

Authors: SADLER, DANIEL - University Arkansas For Medical Sciences (UAMS); TREAS, LILLIE - Arkansas Children'S Hospital; ROSS, TAYLOR - Arkansas Children'S Hospital; SIKE, JAMES - Arkansas Children'S Hospital; BRITTON, STEVEN - University Of Michigan; KOCH, LAUREN - University Of Toledo; BORSHEIM, ELISABET - University Arkansas For Medical Sciences (UAMS); PORTER, CRAIG - University Arkansas For Medical Sciences (UAMS)

Submitted to: Physiological Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2023
Publication Date: 2/1/2024
Citation: Sadler, D., Treas, L., Ross, T., Sike, J., Britton, S., Koch, L., Borsheim, E., Porter, C. 2024. Parental cardiorespiratory fitness influences early life energetics and metabolic health. Physiological Genomics. 56(2):145-157. https://doi.org/10.1152/physiolgenomics.00045.2023.
DOI: https://doi.org/10.1152/physiolgenomics.00045.2023

Interpretive Summary: Inherited cardiorespiratory fitness (CRF) influences early life bioenergetics and metabolic health. Higher intrinsic CRF is associated with greater leanness and improved glucose tolerance in early life. This metabolic phenotype was accompanied by greater mitochondrial respiratory capacity in skeletal muscle, heart, and liver tissue. Proteomic profiling of these three tissues further revealed potential mechanisms linking inherited CRF to early life metabolism.

Technical Abstract: Background: High cardiorespiratory fitness (CRF) is associated with a reduced risk for metabolic disease across the life course. Evidence suggests this may partly be due to superior mitochondrial respiratory function. Objective: To determine the impact of inherited CRF on early life energetics and metabolic health. Methods: Adult rats selectively bred for low (low-capacity runners, LCR) and high (high-capacity runners, HCR) running capacity were metabolically phenotyped prior to being mated. Thereafter, LCR and HCR weanlings were studied at 4-6 weeks of age. Whole body energetics and behavior were evaluated by housing rats in metabolic cages. Mitochondrial respiratory function in permeabilized soleus, heart and liver from adults and weanlings were evaluated by high-resolution respirometry. Proteomic signatures of soleus, heart and liver were determined in both adults and weanlings using quantitative proteomics. Results: Adult HCR had lower body mass and impaired glucose tolerance compared to adult LCR. Body mass-adjusted total energy expenditure (TEE) of adult HCR was higher than LCR, which was partly due to greater physical activity. Soleus and heart mitochondrial respiratory capacities of adult HCR were greater than adult LCR. Proteomic signatures of adult HCR soleus revealed higher abundance of proteins involved in lipid catabolism when compared with adult LCR. LCR and HCR weanlings had comparable body mass, but HCR weanlings had less relative fat mass than LCR weanlings. Glucose tolerance was greater in juvenile HCR than LCR, which coincided with higher body mass-adjusted TEE and physical activity levels. Both coupled and non-coupled respiratory capacities of soleus, heart and liver were higher in HCR weanlings when compared to LCR weanlings. Proteomic signatures indicated a greater capacity for lipid oxidation in contractile muscle, and lower sulfation capacity in liver tissue, of HCR weanlings than LCR weanlings. Conclusion: Inherited CRF influences early life energetics. Proteomic and respirometry analyses indicate that offspring endowed with high CRF have greater capacity for lipid catabolism and oxidative phosphorylation compared to those endowed with low CRF, and that this bioenergetic phenotype influences early-life body composition and metabolic health.