The effects of resistance exercise training on macro- and micro-circulatory responses to feeding and skeletal muscle protein anabolism in older men

Abstract

Key points: Increases in limb blood flow in response to nutrition are reduced in older age. Muscle microvascular blood flow (MBF) in response to nutrition is also reduced with advancing age and this may contribute to age-related 'anabolic resistance'. Resistance exercise training (RET) can rejuvenate limb blood flow responses to nutrition in older individuals. We report here that 20 weeks of RET also restores muscle MBF in older individuals. Restoration of MBF does not, however, enhance muscle anabolic responses to nutrition.

Abstract: The anabolic effects of dietary protein on skeletal muscle depend on adequate skeletal muscle perfusion, which is impaired in older people. This study explores fed state muscle microvascular blood flow, protein metabolism and exercise training status in older men. We measured leg blood flow (LBF), muscle microvascular blood volume (MBV) and muscle protein turnover under post-absorptive and fed state (i.v. Glamin to double amino acids, dextrose to sustain glucose ∼7-7.5 mmol l(-1) ) conditions in two groups: 10 untrained men (72.3 ± 1.4 years; body mass index (BMI) 26.5 ± 1.15 kg m(2) ) and 10 men who had undertaken 20 weeks of fully supervised, whole-body resistance exercise training (RET) (72.8 ± 1.4 years; BMI 26.3 ± 1.2 kg m(2) ). We measured LBF by Doppler ultrasound and muscle MBV by contrast-enhanced ultrasound. Muscle protein synthesis (MPS) was measured using [1, 2-(13) C2 ] leucine with breakdown (MPB) and net protein balance (NPB) by ring-[D5 ] phenylalanine tracers. Plasma insulin was measured via ELISA and indices of anabolic signalling (e.g. Akt/mTORC1) by immunoblotting from muscle biopsies. Whereas older untrained men did not exhibit fed-state increases in LBF or MBV, the RET group exhibited increases in both LBF and MBV. Despite our hypothesis that enhanced fed-state circulatory responses would improve anabolic responses to nutrition, fed-state increases in MPS (∼50-75%; P < 0.001) were identical in both groups. Finally, whereas only the RET group exhibited fed-state suppression of MPB (∼-38%; P < 0.05), positive NPB achieved was similar in both groups. We conclude that RET enhances fed-state LBF and MBV and restores nutrient-dependent attenuation of MPB without robustly enhancing MPS or NPB.

© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Figures

Figure 1

Acute study protocol

Figure 2

Femoral artery blood flow Femoral artery blood flow in untrained subjects (Old) and subjects after 20 weeks of resistance exercise training (Old RET) in post-absorptive and fed conditions (102 mg kg h−1 Glamin and 20% dextrose to maintain blood glucose at 7–7.5 mmol l−1). Values are means ± SEM for n = 10 in each group. *P < 0.05 vs. post-absorptive in the same group; #P < 0.05 vs. Old in the same condition. Analysis via ANOVA, with Bonferroni post hoc analysis.

Figure 3

Microvascular refilling curves A and C, microvascular refilling curves after destruction of perflutren micro-bubbles in untrained (Old) subjects (A) and older subjects after 20 weeks of resistance exercise training (Old RET) (C) in post-absorptive and fed conditions (102 mg kg h−1 Glamin and 20% dextrose to maintain blood glucose at 7–7.5 mmol l−1). A = plateau value; β = flow rate constant. B and D, microvascular blood volume presented as the plateau value acoustic index (A value) in Old (B) and Old RET subjects (D). Values are means ± SEM for n = 10 in each group. ***P < 0.001 vs. post-absorptive in the same group. Analysis via paired Student’s t test.

Figure 4

Myofibrillar fractional synthetic rate, rate of disappearance, rate of appearance and net protein balance Myofibrillar fractional synthetic rate (FSR) (A), rate of disappearance (B), rate of appearance (C) and net protein balance (D) in response to feeding (102 mg kg h−1 Glamin and 20% dextrose to maintain blood glucose at 7–7.5 mmol l−1) in untrained subjects (Old) and older subjects after 20 weeks of resistance exercise training (Old RET). Values are means ± SEM for n = 10 in each group. *P < 0.05 vs. post-absorptive in the same group; **P < 0.01 vs. post-absorptive in the same group; ***P < 0.001 vs. post-absorptive in the same group. Analysis via ANOVA, with Bonferroni post hoc analysis.

Figure 5

Plasma insulin and dextrose infusion required to maintain blood glucose Plasma insulin values (A) and dextrose infusion required to maintain a blood glucose value of 7–7.5 mmol l−1 (B) in untrained (Old) and older subjects after 20 weeks of resistance exercise training (Old RET). Values for n = 10 in each group.

Figure 6

Phosphorylation of AKT and P70S6K1 in response to feeding Phosphorylation of AKT (A) and P70S6K1 (B) in response to feeding (102 mg kg h−1 Glamin and 20% dextrose to maintain blood glucose at 7–7.5 mmol l−1) in untrained subjects (Old) and older subjects after 20 weeks of resistance exercise training (Old RET). Values are arbitrary density metric units (AU) with means ± SEM for n = 10 in each group. *P < 0.05 vs. post-absorptive in the same group. Analysis via ANOVA, with Bonferroni post hoc analysis.