Sustained Exercise Endurance Capacity after Depletion of Liver Glycogen Levels

Author(s):  
Stephanus E. Terblanche ◽  
Kishor Gohil ◽  
Johanna K. Lang ◽  
Lester Packer
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Koji Takemura ◽  
Hiroshi Nishi ◽  
Takaaki Higashihara ◽  
Masaomi Nangaku

Abstract Background and Aims Erythropoietin (EPO) and hypoxia-inducible factor (HIF) stabilizers (prolyl hydroxylase (PH) inhibitors) are efficient therapeutic modalities against anemia in chronic kidney disease (CKD). Compared to EPO and EPO receptor system, extra-renal action of PH inhibitors has still not been fully investigated. Previous reports caution us about the actual misuse of PH inhibitors in doped athletes, but the drug nonhematopoietic effects of PH inhibitors on skeletal muscles remain controversial both in healthy subjects or in patients with CKD. Method To study direct pharmacological effects of PH inhibitors on skeletal muscles, one of PH inhibitors, roxadustat, was administered via oral gavage to healthy 8-week-old C57BL6 mice. Plasma EPO levels and HIF-targeted gene expression were analyzed after a single administration. Exercise ability was assessed by treadmill exhaustion test after a single dose or chronic 5-week treatment. Roxadustat was also administered for 2 weeks to CKD mice with 2-week 0.2% adenine diet. Endurance capacity was similarly assessed after 2-week roxadustat treatment. Results Even a single administration of roxadustat increased plasma EPO levels and gene expression downstream of HIF in skeletal muscles. Healthy mice treated with roxadustat for 5 weeks showed higher blood haemoglobin (Hb) levels and improved exercise endurance in treadmill exhaustion test, which was blunted by hemodilution procedure. Adenine-fed CKD mice showed lower blood Hb levels and worse endurance capacity compared to control mice. Roxadustat treatment improved endurance capacity in CKD mice without significant increase in blood Hb levels compared to control mice. Conclusion Treatment with HIF-PH inhibitor, roxadustat, improves exercise endurance principally via pharmacological erythropoiesis. However, roxadustat shows potential effects independent of erythropoiesis on endurance capacity in CKD.


2005 ◽  
Vol 16 (1) ◽  
pp. 37
Author(s):  
P Palange ◽  
G Valli ◽  
P Onorati ◽  
R Antonucci ◽  
P Paoletti ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tatsuya Iso ◽  
Hikari Haruyama ◽  
Hiroaki Sunaga ◽  
Miki Matsui ◽  
Hiroki Matsui ◽  
...  

2008 ◽  
Vol 40 (9) ◽  
pp. 1637-1644 ◽  
Author(s):  
JASON K.W. LEE ◽  
SUSAN M. SHIRREFFS ◽  
RONALD J. MAUGHAN

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0152562 ◽  
Author(s):  
Andrew C. Betik ◽  
Jay Aguila ◽  
Glenn K. McConell ◽  
Andrew J. McAinch ◽  
Michael L. Mathai

2013 ◽  
Vol 304 (2) ◽  
pp. H206-H214 ◽  
Author(s):  
Steven W. Copp ◽  
Tadakatsu Inagaki ◽  
Michael J. White ◽  
Daniel M. Hirai ◽  
Scott K. Ferguson ◽  
...  

Consumption of the dietary flavanol (−)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI ( n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O2 uptake (V̇o2 peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O2 pressure (Po2mv) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓∼5%) resting ( P = 0.03) and exercising ( P = 0.04) MAP. There were no differences in exercise endurance capacity, V̇o2 peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min−1·100 g−1, P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min−1·100 g−1·mmHg−1, P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓∼16%) but did not impact resting Po2mv or any kinetics parameters ( P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg−1·day−1) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats.


2009 ◽  
Vol 297 (2) ◽  
pp. E505-E513 ◽  
Author(s):  
Elisabeth Huijsman ◽  
Caro van de Par ◽  
Catherine Economou ◽  
Chris van der Poel ◽  
Gordon S. Lynch ◽  
...  

Adipose triacylglycerol lipase (ATGL) and hormone-sensitive lipase (HSL) are essential for efficient lipolysis in adipose tissue and skeletal muscle. Herein, we utilized whole body knockout mice to address the importance of ATGL and HSL for metabolic function and exercise performance. ATGL deletion severely disrupts whole-body substrate partitioning at rest; reducing plasma free fatty acid (FFA) availability (WT: 0.49 ± 0.06 vs. ATGL−/− 0.34 ± 0.03 mM), which in turn enhances carbohydrate oxidation during fasting (mean RER, WT: 0.86 ± 0.02, ATGL−/− 0.90 ± 0.01) and is associated with depleted muscle and liver glycogen stores. While plasma FFA was modestly reduced (23%) and whole body carbohydrate metabolism increased in HSL−/− mice, resting glycogen storage was not compromised. Studies in isolated muscles revealed that the capacity of ATGL and HSL−/− muscle to transport exogenous fatty acids is not compromised and the capacity to oxidize fatty acids is actually increased (3.7- and 1.3-fold above WT for ATGL and HSL). The exercise-induced increase in plasma FFA and glycerol was blunted with ATGL or HSL deletion, demonstrating an impaired capacity for exercise-induced lipolysis in these mice. Carbohydrate oxidation was increased concomitantly during exercise in ATGL−/− and HSL−/− mice, resulting in more muscle and liver glycogen depletion. Maximal running velocity and endurance capacity were reduced by 42% and 46% in ATGL−/− mice, but not in HSL−/− mice. The reduction in performance in ATGL−/− mice was not due to defective muscle contractile performance. These results demonstrate an essential role for both ATGL and HSL in maintaining adequate FFA supply to sustain normal substrate metabolism at rest and during exercise.


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