Limb Blood Flow Restriction Plus Mild Aerobic Exercise Training Protects the Heart Against Isoproterenol-Induced Cardiac Injury in Old Rats: Role of GSK-3β

Abstract Aerobic exercise training is a potent intervention for the treatment and prevention of age-related disease, such as heart disease, obesity, and Type 2 Diabetes. Insulin resistance, a hallmark of Type 2 Diabetes, is reversed in response to aerobic exercise training. However, the effect of aerobic exercise training on glucagon sensitivity is unclear. Glucagon signaling at the liver promotes fatty acid oxidation, inhibits De novo lipogenesis, and activates AMP Kinase, a key mediator of healthy aging. Like humans, aging in mice age leads to a decline in physical and metabolic function. To understand the role of glucagon signaling in exercise-induced improvements in physical and metabolic function in the mouse, we implemented a 16-week aerobic exercise training protocol in young and aged mice. 16 weeks of exercise training initiated at 6 months of age increased markers of physical function (P<0.01) and attenuated age-related weight gain (P<0.05) and fat mass (P<0.0001). Additionally, exercise training improved glucose clearance (P<0.01), enhanced glucose-stimulated insulin secretion (P<0.01) and decreased hepatic lipid accumulation (P<0.05). Importantly, exercise training decreased hypoglycemia stimulated glucagon secretion (P<0.01), with no effect on hepatic glucagon receptor mRNA expression or serum glucagon. Thus, we propose that aerobic exercise training enhances glucagon sensitivity at the liver, implicating glucagon as a potential mediator of exercise-induced improvements in aging. Studies initiating the same aerobic exercise training intervention at 18 months of age in the mouse are currently underway to establish the role of glucagon receptor signaling in exercise-induced improvements in aging.

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A novel gravity-induced blood flow restriction model augments ACC phosphorylation and PGC-1α mRNA in human skeletal muscle following aerobic exercise: a randomized crossover study

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2019-0641 ◽

2020 ◽

Vol 45 (6) ◽

pp. 641-649 ◽

Cited By ~ 2

Author(s):

Nicholas Preobrazenski ◽

Hashim Islam ◽

Patrick J. Drouin ◽

Jacob T. Bonafiglia ◽

Michael E. Tschakovsky ◽

...

Keyword(s):

Blood Flow ◽

Aerobic Exercise ◽

Messenger Rna ◽

Muscle Activation ◽

Peak Oxygen Uptake ◽

Work Rate ◽

Muscle Oxygenation ◽

Flow Restriction ◽

Acetyl Coenzyme A Carboxylase

This study tested the hypothesis that a novel, gravity-induced blood flow restricted (BFR) aerobic exercise (AE) model will result in greater activation of the AMPK–PGC-1α pathway compared with work rate-matched non-BFR. Thirteen healthy males (age: 22.4 ± 3.0 years; peak oxygen uptake: 42.4 ± 7.3 mL/(kg·min)) completed two 30-min work rate-matched bouts of cycling performed with their legs below (CTL) and above their heart (BFR) at ∼2 weeks apart. Muscle biopsies were taken before, immediately, and 3 h after exercise. Blood was drawn before and immediately after exercise. Our novel gravity-induced BFR model led to less muscle oxygenation during BFR compared with CTL (O2Hb: p = 0.01; HHb: p < 0.01) and no difference in muscle activation (p = 0.53). Plasma epinephrine increased following both BFR and CTL (p < 0.01); however, only norepinephrine increased more following BFR (p < 0.01). PGC-1α messenger RNA (mRNA) increased more following BFR (∼6-fold) compared with CTL (∼4-fold; p = 0.036). VEGFA mRNA increased (p < 0.01) similarly following BFR and CTL (p = 0.21), and HIF-1α mRNA did not increase following either condition (p = 0.21). Phosphorylated acetyl-coenzyme A carboxylase (ACC) increased more following BFR (p < 0.035) whereas p-PKA substrates, p-p38 MAPK, and acetyl-p53 increased (p < 0.05) similarly following both conditions (p > 0.05). In conclusion, gravity-induced BFR is a viable BFR model that demonstrated an important role of AMPK signalling on augmenting PGC-1α mRNA. Novelty Gravity-induced BFR AE reduced muscle oxygenation without impacting muscle activation, advancing gravity-induced BFR as a simple, inexpensive BFR model. Gravity-induced BFR increased PGC-1α mRNA and ACC phosphorylation more than work rate-matched non-BFR AE. This is the first BFR AE study to concurrently measure blood catecholamines, muscle activation, and muscle oxygenation.

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