Biology subjects

Borsheim, E.

Publications and source records attributed to Borsheim, E..

3 recordsLinked to original sources

bioRxiv2026

Inborn cardiorespiratory fitness and exercise training modulate brown adipose tissue function and plasticity in early life

This study aimed to determine the impact of inborn metabolic fitness and early life exercise training on whole body and brown adipose tissue (BAT) energetics. We carried out comprehensive metabolic phenotyping on 4-week old rats bred for high (high-capacity runner, HCR) and low (low-capacity runner, LCR) running capacity following randomization to voluntary wheel running (VWR) or control (CRTL) for 6-weeks. High-resolution respirometry and untargeted proteomics were then employed to determine the impact of inborn fitness and early life exercise on BAT function. When accounting for differences in body mass, early life exercise (VWR) resulted in greater basal and total energy expenditure, irrespective of strain (P < 0.0001 for both). Both leak and uncoupling protein 1 (UCP1) dependent respiratory capacities in isolated BAT mitochondria were greater in rats randomized to VWR compared to CTRL in both HCR (P < 0.01) and LCR (P < 0.05) strains. Similarly, mitochondrial sensitivity to the UCP1 inhibitor GDP was greater in both HCR (P < 0.01) and LCR (P < 0.05) rats randomized to VWR versus control. The BAT proteome differed in CTRL HCR and LCR rats, were there was enrichment in proteins related to branched chain oxidation and mitochondrial fatty acid oxidation in HCR rats. VWR remodeled the BAT proteome, where 151 proteins were differentially expressed in LCR BAT and 209 differentially expressed in LCR BAT following VWR. In both stains, there was an enrichment in proteins related to metabolism mitochondrial function in response to VWR. However, when comparing strains, 39 proteins were differentially expressed in BAT in HCR rats compared to LCR rats in response to VWR. These proteins were related to carboxylic acid and amino acid metabolism. Collectively, inborn fitness impacts body mass and composition, exercise behaviors, and the BAT proteome in early life. Early life exercise alters whole body and BAT energetics irrespective of inborn fitness, augmenting basal and total energy expenditure and BAT thermogenic capacity and function.

physiology↗

bioRxiv2026

Carnitine deficiency alters fuel metabolism and voluntary wheel running in mice

BackgroundCarnitine plays an obligatory role in energetics owing to its role in the translocation of long-chain fatty acids into the mitochondrion for oxidation. Here, we determined the metabolic and behavioral consequences of systemic carnitine deficiency (SCD) in mice. MethodsFemale C57BL/6J mice were randomized to receive normal drinking water (control, n = 8) or drinking water supplemented with mildronate 4g.L-1 (mildronate, n = 8) for 21 days. Body composition was assessed at baseline and post treatment. Metabolic and behavioral phenotyping was performed continuously over 72 hours following 14 days of control or mildronate treatment. Stable isotope were used to assess whole-body substrate oxidation. Carnitine subfractions were quantified in skeletal muscle and liver, as was mitochondrial respiratory function. Liver and muscle samples also underwent proteomic analysis. ResultsMildronate treatment depleted total carnitine in muscle and liver by [~]97% (P < 0.001) and [~]90% (P < 0.001), respectively. Carnitine depletion was accompanied by lower total energy expenditure (P = 0.01), attributable to lower voluntary wheel running (P = 0.01). Oxidation rates of palmitate (P < 0.01) but not octanoate were lower whereas rates of glucose oxidation were greater in carnitine depleted mice (P < 0.01). Mitochondrial respiratory capacity was unaltered by carnitine deficiency. Carnitine deficiency remodeled muscle and liver proteomes to support lipid oxidation and energy production. SummaryIn mice, carnitine deficiency is characterized by decreased long-chain fatty acid oxidation despite preserved mitochondrial respiratory capacity. Carnitine deficiency resulted in lower voluntary exercise and a concomitant reduction in energy expenditure.

physiology↗

bioRxiv2024

Shared and distinct adaptations to early-life exercise training based on inborn fitness

BackgroundLow cardiorespiratory fitness due to genetics increases the risk for cardiometabolic disease. Endurance exercise training promotes cardiorespiratory fitness and improves cardiometabolic risk factors, but with great heterogeneity. Here, we tested the hypothesis that the metabolic phenotype imparted by low parental (inborn) cardiorespiratory fitness would be overcome by early-life exercise training, and that exercise adaptations would be influenced in part by inborn fitness. MethodsAt 26 days of age, male and female rat low-capacity runners (LCR, n=20) and high-capacity runners (HCR, n=20) generated by artificial selection were assigned to either sedentary control (CTRL, n=10) or voluntary wheel running (VWR, n=10) for 6 weeks. Post-intervention, whole-body metabolic phenotyping was performed, and the respiratory function of isolated skeletal muscle and liver mitochondria assayed. Transcriptomics and proteomics were performed on skeletal muscle and liver tissue using RNA-sequencing and mass spectrometry, respectively. ResultsDaily VWR volume was 1.8-fold higher in HCR-VWR compared to LCR-VWR. In LCR, VWR reduced adiposity and enhanced glucose tolerance, coincident with elevated total energy expenditure. While intrinsic skeletal muscle mitochondrial respiratory function was unaffected by VWR, estimated skeletal muscle oxidative capacity increased in VWR groups owing to greater mitochondrial content. In the liver, both maximal oxidative capacity and ATP-linked respiration were higher in HCR-VWR than HCR-CTRL. Transcriptomic and proteomic profiling revealed extensive remodeling of skeletal muscle and liver tissue by VWR, elements of which were both shared and distinct based on inborn fitness. SummaryEarly-life exercise training partially overcomes the metabolic phenotype imparted by low inborn cardiorespiratory fitness. However, molecular adaptations to VWR are partly influenced by inborn fitness, which may have implications for personalized exercise medicine.

physiology↗