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Article ; Online: A focus on leucine in the nutritional regulation of human skeletal muscle metabolism in ageing, exercise and unloading states.

Ely, Isabel A / Phillips, Bethan E / Smith, Kenneth / Wilkinson, Daniel J / Piasecki, Mathew / Breen, Leigh / Larsen, Mads S / Atherton, Philip J

Clinical nutrition (Edinburgh, Scotland)

2023 Volume 42, Issue 10, Page(s) 1849–1865

Abstract: Muscle protein synthesis (MPS) and muscle protein breakdown (MPB) are influenced through dietary protein intake and physical (in)activity, which it follows, regulate skeletal muscle (SKM) mass across the lifespan. Following consumption of dietary protein, ...

Abstract	Muscle protein synthesis (MPS) and muscle protein breakdown (MPB) are influenced through dietary protein intake and physical (in)activity, which it follows, regulate skeletal muscle (SKM) mass across the lifespan. Following consumption of dietary protein, the bio-availability of essential amino acids (EAA), and primarily leucine (LEU), drive a transient increase in MPS with an ensuing refractory period before the next MPS stimulation is possible (due to the "muscle full" state). At the same time, MPB is periodically constrained via reflex insulin actions. Layering exercise on top of protein intake increases the sensitivity of SKM to EAA, therefore extending the muscle full set-point (∼48 h), to permit long-term remodelling (e.g., hypertrophy). In contrast, ageing and physical inactivity are associated with a premature muscle full set-point in response to dietary protein/EAA and contractile activity. Of all the EAA, LEU is the most potent stimulator of the mechanistic target of rapamycin complex 1 (mTORC1)-signalling pathway, with the phosphorylation of mTORC1 substrates increasing ∼3-fold more than with all other EAA. Furthermore, maximal MPS stimulation is also achieved following low doses of LEU-enriched protein/EAA, negating the need for larger protein doses. As a result, LEU supplementation has been of long term interest to maximise muscle anabolism and subsequent net protein accretion, especially when in tandem with resistance exercise. This review highlights current knowledge vis-à-vis the anabolic effects of LEU supplementation in isolation, and in enriched protein/EAA sources (i.e., EAA and/or protein sources with added LEU), in the context of ageing, exercise and unloading states.
MeSH term(s)	Humans ; Leucine/metabolism ; Dietary Proteins/metabolism ; Muscle, Skeletal/metabolism ; Amino Acids, Essential/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mechanistic Target of Rapamycin Complex 1/pharmacology ; Aging/metabolism ; Muscle Proteins/metabolism
Chemical Substances	Leucine (GMW67QNF9C) ; Dietary Proteins ; Amino Acids, Essential ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Muscle Proteins
Language	English
Publishing date	2023-08-12
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2023.08.010
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Article ; Online: Onset of androgen deprivation therapy leads to rapid deterioration of body composition, physical performance, cardiometabolic health and quality-of-life in prostate cancer patients.

Overkamp, Maarten / Houben, Lisanne H P / van der Meer, Saskia / van Roermund, Joep G H / Bos, Ronald / Kokshoorn, Arjan P J / Larsen, Mads S / van Loon, Luc J C / Beelen, Milou / Beijer, Sandra

Scandinavian journal of urology

2023 Volume 57, Issue 1-6, Page(s) 60–66

Abstract: Objectives: To assess the adverse impact of the first 5 months of androgen deprivation therapy on body composition, physical performance, cardiometabolic health and health-related quality-of-life in prostate cancer patients.: Materials and methods: ... ...

Abstract	Objectives: To assess the adverse impact of the first 5 months of androgen deprivation therapy on body composition, physical performance, cardiometabolic health and health-related quality-of-life in prostate cancer patients. Materials and methods: Thirty-four prostate cancer patients (70 ± 7 years) were assessed shortly after initiation of androgen deprivation therapy and again 5 months thereafter. Measurements consisted of whole-body dual-energy x-ray absorptiometry (body composition), computed tomography scanning of the upper leg (muscle mass), one-repetition maximum leg press (muscle strength), cardiopulmonary exercise testing (aerobic capacity), blood draws (metabolic parameters), accelerometry (habitual physical activity) and questionnaires (health-related quality-of-life). Data were analyzed with Student's paired Results: Over time, whole-body fat mass (from 26.2 ± 7.7 to 28.4 ± 8.3 kg, Conclusions: Androgen deprivation therapy induces adverse changes in body composition, muscle strength, cardiometabolic health and health-related quality-of-life already within 5 months after the start of treatment, possibly largely contributed by diminished habitual physical activity. Prostate cancer patients should, therefore, be stimulated to increase their habitual physical activity immediately after initiation of androgen deprivation therapy, to limit adverse side-effects and to improve health-related quality-of-life.
MeSH term(s)	Male ; Humans ; Prostatic Neoplasms/therapy ; Androgen Antagonists/therapeutic use ; Androgens/pharmacology ; Androgens/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Body Composition ; Physical Functional Performance ; Quality of Life ; Cardiovascular Diseases ; Exercise Therapy
Chemical Substances	Androgen Antagonists ; Androgens ; Antineoplastic Agents, Hormonal
Language	English
Publishing date	2023-01-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2701936-6
ISSN	2168-1813 ; 2168-1805
ISSN (online)	2168-1813
ISSN	2168-1805
DOI	10.1080/21681805.2023.2168050
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Article ; Online: Dose-Response of Myofibrillar Protein Synthesis To Ingested Whey Protein During Energy Restriction in Overweight Postmenopausal Women: A Randomized, Controlled Trial.

Larsen, Mads S / Witard, Oliver C / Holm, Lars / Scaife, Paula / Hansen, Rikke / Smith, Kenneth / Tipton, Kevin D / Mose, Maike / Bengtsen, Mads B / Lauritsen, Katrine M / Mikkelsen, Ulla R / Hansen, Mette

The Journal of nutrition

2023 Volume 153, Issue 11, Page(s) 3173–3184

Abstract: Background: Diet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well ... ...

Abstract	Background: Diet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well characterized during energy balance but limited data exist under conditions of energy restriction in clinical populations. Objective: To determine the dose-response of MPS to ingested whey protein following short-term diet-induced energy restriction in overweight, postmenopausal, women at rest and postexercise. Design: Forty middle-aged (58.6±0.4 y), overweight (BMI: 28.6±0.4), postmenopausal women were randomly assigned to 1 of 4 groups: Three groups underwent 5 d of energy restriction (∼800 kcal/d). On day 6, participants performed a unilateral leg resistance exercise bout before ingesting either a bolus of 15g (ERW15, n = 10), 35g (ERW35, n = 10) or 60g (ERW60, n = 10) of whey protein. The fourth group (n = 10) ingested a 35g whey protein bolus after 5 d of an energy balanced diet (EBW35, n = 10). Myofibrillar fractional synthetic rate (FSR) was calculated under basal, fed (FED) and postexercise (FED-EX) conditions by combining an L-[ring- Results: Myofibrillar FSR was greater in ERW35 (0.043±0.003%/h, P = 0.013) and ERW60 (0.042±0.003%/h, P = 0.026) than ERW15 (0.032 ± 0.003%/h), with no differences between ERW35 and ERW60 (P = 1.000). Myofibrillar FSR was greater in FED (0.044 ± 0.003%/h, P < 0.001) and FED-EX (0.048 ± 0.003%/h, P < 0.001) than BASAL (0.027 ± 0.003%/h), but no differences were detected between FED and FED-EX (P = 0.732) conditions. No differences in myofibrillar FSR were observed between EBW35 (0.042 ± 0.003%/h) and ERW35 (0.043 ± 0.003%/h, P = 0.744). Conclusion: A 35 g dose of whey protein, ingested with or without resistance exercise, is sufficient to stimulate a maximal acute response of MPS following short-term energy restriction in overweight, postmenopausal women, and thus may provide a per serving protein recommendation to mitigate muscle loss during a weight loss program. Trial registry: clinicaltrials.gov (ID: NCT03326284).
MeSH term(s)	Middle Aged ; Humans ; Female ; Whey Proteins ; Overweight/metabolism ; Postmenopause ; Diet, Reducing ; Muscle, Skeletal/metabolism ; Muscle Proteins/metabolism ; Resistance Training
Chemical Substances	Whey Proteins ; Muscle Proteins
Language	English
Publishing date	2023-08-19
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1016/j.tjnut.2023.08.011
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Article ; Online: Presleep Protein Supplementation Does Not Improve Recovery During Consecutive Days of Intense Endurance Training: A Randomized Controlled Trial.

Larsen, Mads S / Clausen, Dagmar / Jørgensen, Astrid Ank / Mikkelsen, Ulla R / Hansen, Mette

International journal of sport nutrition and exercise metabolism

2019 Volume 29, Issue 4, Page(s) 426–434

Abstract: Recent studies demonstrate that protein ingestion immediately before sleep improves muscle recovery during the night following resistance exercise. Whether this feeding strategy benefits recovery from endurance training has yet to be established. The aim ...

Abstract	Recent studies demonstrate that protein ingestion immediately before sleep improves muscle recovery during the night following resistance exercise. Whether this feeding strategy benefits recovery from endurance training has yet to be established. The aim of this study was to investigate the effects of whey protein isolate ingested every night before sleep on subsequent performance and circulatory markers of muscular recovery during a week of intensified endurance training mimicking a training camp. In a parallel design, 32 trained runners underwent a 1-week intervention with a rigorously controlled diet (carbohydrate = 7.2 g·kg
MeSH term(s)	Adult ; Athletic Performance ; Creatine Kinase/blood ; Dietary Carbohydrates ; Dietary Supplements ; Double-Blind Method ; Endurance Training ; Humans ; L-Lactate Dehydrogenase/blood ; Male ; Myoglobin/blood ; Running ; Sleep ; Sports Nutritional Physiological Phenomena ; Whey Proteins/administration & dosage ; Young Adult
Chemical Substances	Dietary Carbohydrates ; Myoglobin ; Whey Proteins ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Creatine Kinase (EC 2.7.3.2)
Language	English
Publishing date	2019-07-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1101115-4
ISSN	1543-2742 ; 1050-1606 ; 1526-484X
ISSN (online)	1543-2742
ISSN	1050-1606 ; 1526-484X
DOI	10.1123/ijsnem.2018-0286
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Article: Effects of protein intake prior to carbohydrate-restricted endurance exercise: a randomized crossover trial

Larsen, Mads S / Holm, Lars / Svart, Mads V / Hjelholt, Astrid J / Bengtsen, Mads B / Dollerup, Ole L / Dalgaard, Line B / Vendelbo, Mikkel H / van Hall, Gerrit / Møller, Niels / Mikkelsen, Ulla R / Hansen, Mette

Journal of the International Society of Sports Nutrition. 2020 Dec., v. 17, no. 1

2020

Abstract: BACKGROUND: Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested ... ...

Abstract	BACKGROUND: Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested prior to training as a means to enhance the protein balance during exercise without spoiling the effect of the low carbohydrate availability. Accordingly, this is being practiced by world class athletes. However, the effect of protein intake on muscle protein metabolism during training low has not been studied. This study aimed to examine if protein intake prior to exercise with reduced carbohydrate stores benefits muscle protein metabolism in exercising and non-exercising muscles. METHODS: Nine well-trained subjects completed two trials in random order both of which included a high-intensity interval ergometer bike ride (day 1), a morning (day 2) steady state ride (90 min at 65% VO₂peak, 90ss), and a 4-h recovery period. An experimental beverage was consumed before 90ss and contained either 0.5 g whey protein hydrolysate [WPH]/ kg lean body mass or flavored water [PLA]. A stable isotope infusion (L-[ring-¹³C₆]-phenylalanine) combined with arterial-venous blood sampling, and plasma flow rate measurements were used to determine forearm protein turnover. Myofibrillar protein synthesis was determined from stable isotope incorporation into the vastus lateralis. RESULTS: Forearm protein net balance was not different from zero during 90ss exercise (nmol/100 ml/min, PLA: 0.5 ± 2.6; WPH: 1.8, ± 3.3) but negative during the 4 h recovery (nmol/100 ml/min, PLA: − 9.7 ± 4.6; WPH: − 8.7 ± 6.5); no interaction (P = 0.5) or main effect of beverage (P = 0.11) was observed. Vastus lateralis myofibrillar protein synthesis rates were increased during 90ss exercise (+ 0.02 ± 0.02%/h) and recovery (+ 0.02 ± 0.02%/h); no interaction (P = 0.3) or main effect of beverage (P = 0.3) was observed. CONCLUSION: We conclude that protein ingestion prior to endurance exercise in the energy- and carbohydrate-restricted state does not increase myofibrillar protein synthesis or improve net protein balance in the exercising and non-exercising muscles, respectively, during and in the hours after exercise compared to ingestion of a non-caloric control. TRIAL REGISTRATION: clinicaltrials.gov, NCT01320449. Registered 10 May 2017 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03147001
Keywords	arms (limbs) ; athletes ; beverages ; blood plasma ; blood sampling ; carbohydrates ; cross-over studies ; energy ; exercise ; ingestion ; lean body mass ; muscle protein ; muscles ; protein hydrolysates ; protein intake ; protein synthesis ; sports nutrition ; stable isotopes ; whey protein
Language	English
Dates of publication	2020-12
Size	p. 7.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2162810-5
ISSN	1550-2783
ISSN	1550-2783
DOI	10.1186/s12970-020-0338-z
Database	NAL-Catalogue (AGRICOLA)

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Article: Effects of protein intake prior to carbohydrate-restricted endurance exercise: a randomized crossover trial

Journal of the International Society of Sports Nutrition. 2020 Dec., v. 17, no. 1

2020

Abstract	BACKGROUND: Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested prior to training as a means to enhance the protein balance during exercise without spoiling the effect of the low carbohydrate availability. Accordingly, this is being practiced by world class athletes. However, the effect of protein intake on muscle protein metabolism during training low has not been studied. This study aimed to examine if protein intake prior to exercise with reduced carbohydrate stores benefits muscle protein metabolism in exercising and non-exercising muscles. METHODS: Nine well-trained subjects completed two trials in random order both of which included a high-intensity interval ergometer bike ride (day 1), a morning (day 2) steady state ride (90 min at 65% VO₂peak, 90ss), and a 4-h recovery period. An experimental beverage was consumed before 90ss and contained either 0.5 g whey protein hydrolysate [WPH]/ kg lean body mass or flavored water [PLA]. A stable isotope infusion (L-[ring-¹³C₆]-phenylalanine) combined with arterial-venous blood sampling, and plasma flow rate measurements were used to determine forearm protein turnover. Myofibrillar protein synthesis was determined from stable isotope incorporation into the vastus lateralis. RESULTS: Forearm protein net balance was not different from zero during 90ss exercise (nmol/100 ml/min, PLA: 0.5 ± 2.6; WPH: 1.8, ± 3.3) but negative during the 4 h recovery (nmol/100 ml/min, PLA: − 9.7 ± 4.6; WPH: − 8.7 ± 6.5); no interaction (P = 0.5) or main effect of beverage (P = 0.11) was observed. Vastus lateralis myofibrillar protein synthesis rates were increased during 90ss exercise (+ 0.02 ± 0.02%/h) and recovery (+ 0.02 ± 0.02%/h); no interaction (P = 0.3) or main effect of beverage (P = 0.3) was observed. CONCLUSION: We conclude that protein ingestion prior to endurance exercise in the energy- and carbohydrate-restricted state does not increase myofibrillar protein synthesis or improve net protein balance in the exercising and non-exercising muscles, respectively, during and in the hours after exercise compared to ingestion of a non-caloric control. TRIAL REGISTRATION: clinicaltrials.gov, NCT01320449. Registered 10 May 2017 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03147001
Keywords	arms (limbs) ; beverages ; carbohydrates ; cross-over studies ; exercise ; ingestion ; lean body mass ; muscle protein ; protein hydrolysates ; protein intake ; protein synthesis ; stable isotopes ; whey protein
Language	English
Dates of publication	2020-12
Size	p. 7.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2162810-5
ISSN	1550-2783
ISSN	1550-2783
DOI	10.1186/s12970-020-0338-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Effects of protein intake prior to carbohydrate-restricted endurance exercise: a randomized crossover trial.

Journal of the International Society of Sports Nutrition

2020 Volume 17, Issue 1, Page(s) 7

Abstract: Background: Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested ... ...

Abstract	Background: Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested prior to training as a means to enhance the protein balance during exercise without spoiling the effect of the low carbohydrate availability. Accordingly, this is being practiced by world class athletes. However, the effect of protein intake on muscle protein metabolism during training low has not been studied. This study aimed to examine if protein intake prior to exercise with reduced carbohydrate stores benefits muscle protein metabolism in exercising and non-exercising muscles. Methods: Nine well-trained subjects completed two trials in random order both of which included a high-intensity interval ergometer bike ride (day 1), a morning (day 2) steady state ride (90 min at 65% VO Results: Forearm protein net balance was not different from zero during 90ss exercise (nmol/100 ml/min, PLA: 0.5 ± 2.6; WPH: 1.8, ± 3.3) but negative during the 4 h recovery (nmol/100 ml/min, PLA: - 9.7 ± 4.6; WPH: - 8.7 ± 6.5); no interaction (P = 0.5) or main effect of beverage (P = 0.11) was observed. Vastus lateralis myofibrillar protein synthesis rates were increased during 90ss exercise (+ 0.02 ± 0.02%/h) and recovery (+ 0.02 ± 0.02%/h); no interaction (P = 0.3) or main effect of beverage (P = 0.3) was observed. Conclusion: We conclude that protein ingestion prior to endurance exercise in the energy- and carbohydrate-restricted state does not increase myofibrillar protein synthesis or improve net protein balance in the exercising and non-exercising muscles, respectively, during and in the hours after exercise compared to ingestion of a non-caloric control. Trial registration: clinicaltrials.gov, NCT01320449. Registered 10 May 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03147001.
MeSH term(s)	Adolescent ; Adult ; Bicycling ; Cross-Over Studies ; Diet, Carbohydrate-Restricted ; Dietary Proteins/administration & dosage ; High-Intensity Interval Training ; Humans ; Male ; Middle Aged ; Muscle Proteins/metabolism ; Physical Endurance ; Young Adult
Chemical Substances	Dietary Proteins ; Muscle Proteins
Language	English
Publishing date	2020-01-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2162810-5
ISSN	1550-2783 ; 1550-2783
ISSN (online)	1550-2783
ISSN	1550-2783
DOI	10.1186/s12970-020-0338-z
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Article ; Online: Erythropoietin administration alone or in combination with endurance training affects neither skeletal muscle morphology nor angiogenesis in healthy young men.

Larsen, Mads S / Vissing, Kristian / Thams, Line / Sieljacks, Peter / Dalgas, Ulrik / Nellemann, Birgitte / Christensen, Britt

Experimental physiology

2014 Volume 99, Issue 10, Page(s) 1409–1420

Abstract: The aim was to investigate the ability of an erythropoiesis-stimulating agent (ESA), alone or in combination with endurance training, to induce changes in human skeletal muscle fibre and vascular morphology. In a comparative study, 36 healthy untrained ... ...

Abstract	The aim was to investigate the ability of an erythropoiesis-stimulating agent (ESA), alone or in combination with endurance training, to induce changes in human skeletal muscle fibre and vascular morphology. In a comparative study, 36 healthy untrained men were randomly dispersed into the following four groups: sedentary-placebo (SP, n = 9); sedentary-ESA (SE, n = 9); training-placebo (TP, n = 10); or training-ESA (TE, n = 8). The ESA or placebo was injected once weekly. Training consisted of progressive bicycling three times per week for 10 weeks. Before and after the intervention period, muscle biopsies and magnetic resonance images were collected from the thigh muscles, blood was collected, body composition measured and endurance exercise performance evaluated. The ESA treatment (SE and TE) led to elevated haematocrit, and both ESA treatment and training (SE, TP and TE) increased maximal O2 uptake. With regard to skeletal muscle morphology, TP alone exhibited increases in whole-muscle cross-sectional area and fibre diameter of all fibre types. Also exclusively for TP was an increase in type IIa fibres and a corresponding decrease in type IIx fibres. Furthermore, an overall training effect (TP and TE) was statistically demonstrated in whole-muscle cross-sectional area, muscle fibre diameter and type IIa and type IIx fibre distribution. With regard to muscle vascular morphology, TP and TE both promoted a rise in capillary to muscle fibre ratio, with no differences between the two groups. There were no effects of ESA treatment on any of the muscle morphological parameters. Despite the haematopoietic effects of ESA, we provide novel evidence that endurance training rather than ESA treatment induces adaptational changes in angiogenesis and muscle morphology.
MeSH term(s)	Adaptation, Physiological/drug effects ; Adaptation, Physiological/physiology ; Adolescent ; Adult ; Bicycling/physiology ; Body Composition/drug effects ; Body Composition/physiology ; Erythropoietin/pharmacology ; Exercise/physiology ; Humans ; Male ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/physiology ; Neovascularization, Physiologic/drug effects ; Neovascularization, Physiologic/physiology ; Oxygen Consumption/drug effects ; Oxygen Consumption/physiology ; Physical Endurance/physiology ; Young Adult
Chemical Substances	Erythropoietin (11096-26-7)
Language	English
Publishing date	2014-10
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1016295-1
ISSN	1469-445X ; 0958-0670
ISSN (online)	1469-445X
ISSN	0958-0670
DOI	10.1113/expphysiol.2014.080606
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Article ; Online: Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial.

Christensen, Britt / Nellemann, Birgitte / Larsen, Mads S / Thams, Line / Sieljacks, Peter / Vestergaard, Poul F / Bibby, Bo Martin / Vissing, Kristian / Stødkilde-Jørgensen, Hans / Pedersen, Steen B / Møller, Niels / Nielsen, Søren / Jessen, Niels / Jørgensen, Jens Otto L

American journal of physiology. Endocrinology and metabolism

2013 Volume 305, Issue 7, Page(s) E879–89

Abstract: Unlabelled: Erythropoietin (Epo) administration improves aerobic exercise capacity and insulin sensitivity in renal patients and also increases resting energy expenditure (REE). Similar effects are observed in response to endurance training. The aim was ...

Abstract	Unlabelled: Erythropoietin (Epo) administration improves aerobic exercise capacity and insulin sensitivity in renal patients and also increases resting energy expenditure (REE). Similar effects are observed in response to endurance training. The aim was to compare the effects of endurance training with erythropoiesis-stimulating agent (ESA) treatment in healthy humans. Thirty-six healthy untrained men were randomized to 10 wk of either: 1) placebo (n = 9), 2) ESA (n = 9), 3) endurance training (n = 10), or 4) ESA and endurance training (n = 8). In a single-blinded design, ESA/placebo was injected one time weekly. Training consisted of biking for 1 h at 65% of wattmax three times per week. Measurements performed before and after the intervention were as follows: body composition, maximal oxygen uptake, insulin sensitivity, REE, and palmitate turnover. Uncoupling protein 2 (UCP2) mRNA levels were assessed in skeletal muscle. Fat mass decreased after training (P = 0.003), whereas ESA induced a small but significant increase in intrahepatic fat (P = 0.025). Serum free fatty acid (FFA) levels and palmitate turnover decreased significantly in response to training, whereas the opposite pattern was found after ESA. REE corrected for lean body mass increased in response to ESA and training, and muscle UCP2 mRNA levels increased after ESA (P = 0.035). Insulin sensitivity increased only after training (P = 0.011). In conclusion: 1) insulin sensitivity is not improved after ESA treatment despite improved exercise capacity, 2) the calorigenic effects of ESA may be related to increased UCP2 gene expression in skeletal muscle, and 3) training and ESA exert opposite effects on lipolysis under basal conditions, increased FFA levels and liver fat fraction was observed after ESA treatment.
MeSH term(s)	Adult ; Body Composition/drug effects ; Body Composition/physiology ; Energy Metabolism/drug effects ; Energy Metabolism/physiology ; Erythropoietin/pharmacology ; Humans ; Male ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Oxygen Consumption/drug effects ; Oxygen Consumption/physiology ; Physical Conditioning, Human/physiology ; Physical Endurance/drug effects ; Physical Endurance/physiology ; Treatment Outcome
Chemical Substances	Erythropoietin (11096-26-7)
Language	English
Publishing date	2013-10-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00269.2013
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