Repeated Prolonged Exercise Decreases Maximal Fat Oxidation in Older Men.

INTRODUCTION/PURPOSE: Fat metabolism and muscle adaptation was investigated in six older trained men (age, 61 ± 4 yr; V˙O2max, 48 ± 2 mL·kg·min) after repeated prolonged exercise). METHODS: A distance of 2706 km (1681 miles) cycling was performed over 14 d, and a blood sample and a muscle biopsy were obtained at rest after an overnight fast before and 30 h after the completion of the cycling. V˙O2max and maximal fat oxidation were measured using incremental exercise tests. HR was continuously sampled during cycling to estimate exercise intensity. RESULTS: The daily duration of exercise was 10 h and 31 ± 37 min, and the mean intensity was 53% ± 1% of V˙O2max. Body weight remained unchanged. V˙O2max and maximal fat oxidation rate decreased by 6% ± 2% (P = 0.04) and 32% ± 8% (P < 0.01), respectively. The exercise intensity that elicits maximal fat oxidation was not significantly decreased. Plasma free fatty acid (FA) concentration decreased (P < 0.002) from 500 ± 77 µmol·L to 160 ± 38 µmol·L. Plasma glucose concentration as well as muscle glycogen, myoglobin, and triacylglycerol content remained unchanged. Muscle citrate synthase and ß-hydroxy-acyl-CoA-dehydrogenase activities were unchanged, but the protein expression of HKII, GLUT4, and adipose triacylglycerol lipase were significantly increased. CONCLUSIONS: Overall, the decreased maximal fat oxidation was probably due to lower exogenous plasma fatty acid availability and the muscle adaptation pattern indicates an increased glucose transport capacity and an increased muscle lipolysis capacity supporting an increased contribution of exogenous glucose and endogenous fat during exercise.

Inability to match energy intake with energy expenditure at sustained near-maximal rates of energy expenditure in older men during a 14-d cycling expedition.

BACKGROUND: The upper rates of energy expenditure (EE) and the corresponding regulation of energy intake (EI), as described in younger trained subjects, are not well elucidated in older subjects. OBJECTIVES: The aim was to investigate EE in older men during prolonged cycling and determine whether it is sufficiently matched by EI to maintain energy balance. In addition, we investigated appetite ratings and concentrations of appetite-regulating hormones. DESIGN: Six men (mean ± SE age: 61 ± 3 y) completed 2706 km of cycling, from Copenhagen to Nordkapp, in 14 d. EE was measured by using doubly labeled water, and food and drink intake was recorded by the accompanying scientific staff. Energy balance was calculated as the discrepancy between EI and EE and from changes in body energy stores as derived from deuterium dilution. Fasting hormones were measured before and after cycling, and appetite ratings were recorded twice daily. RESULTS: EE (±SE) increased from 17 ± 1 MJ/d before to 30 ± 2 MJ/d during the cycling trip (P < 0.001), which is equivalent to 4.0 ± 0.1 times the basal metabolic rate. Although body weight remained stable during the 14 d of cycling, body fat decreased (-2.2 ± 0.7 kg; P = 0.02) and fat-free mass increased (2.5 ± 0.6 kg; P = 0.01). EI was 25 ± 1 MJ/d during cycling, resulting in a negative energy balance calculated by the EE - EI gap (-5.2 ± 1.2 MJ/d). Calculated from changes in body energy stores, energy balance was also negative (-4.8 ± 2.0 MJ/d) during the first week. In the morning and evening, hunger ratings increased (both P = 0.02), whereas ratings of fullness decreased in the evening (P = 0.04). Fasting plasma concentrations of insulin increased by 120% ± 15% (P = 0.02), glucagon-like peptide 1 (GLP-1) by 60% ± 20% (P < 0.01), and Polypeptide YY(3-36) by 80% ± 30% (P < 0.02) after cycling. CONCLUSIONS: Older male cyclists sustained near-maximal rates of EE during prolonged cycling but were unable to upregulate EI to maintain energy balance. Despite the presence of increased motivation to eat, a more profound counteracting physiologic stimulus inhibiting increases in EI was present. This trial was registered at clinicaltrials.gov as NCT02353624.

Effects of an 8-weeks erythropoietin treatment on mitochondrial and whole body fat oxidation capacity during exercise in healthy males.

The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial and whole body fatty acid oxidation capacity during exercise, myoglobin concentration and angiogenesis. Recombinant erythropoietin was administered by subcutaneous injections (5000 IU) in six healthy male volunteers (aged 21 ± 2 years; fat mass 18.5 ± 2.3%) over 8 weeks. The participants performed two graded cycle ergometer exercise tests before and after the intervention where VO2max and maximal fat oxidation were measured. Biopsies of the vastus lateralis muscle were obtained before and after the intervention. Recombinant erythropoietin treatment increased mitochondrial O2 flux during ADP stimulated state 3 respiration in the presence of complex I and II substrates (malate, glutamate, pyruvate, succinate) with additional electron input from ß-oxidation (octanoylcarnitine) (from 60 ± 13 to 87 ± 24 pmol · s(-1) · mg(-1) P < 0.01). ß-hydroxy-acyl-CoA-dehydrogenase activity was higher after treatment (P < 0.05), whereas citrate synthase activity also tended to increase (P = 0.06). Total myoglobin increased by 16.5% (P < 0.05). Capillaries per muscle area tended to increase (P = 0.07), whereas capillaries per fibre as well as the total expression of vascular endothelial growth factor remained unchanged. Whole body maximal fat oxidation was not increased after treatment. Eight weeks of recombinant erythropoietin treatment increases mitochondrial fatty acid oxidation capacity and myoglobin concentration without any effect on whole body maximal fat oxidation.

Erythropoietin treatment enhances muscle mitochondrial capacity in humans.

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.