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PURPOSE: Energy deficiency decreases muscle protein synthesis (MPS), possibly due to greater whole-body essential amino acid (EAA) requirements and reliance on energy stores. Whether energy deficit-induced anabolic resistance is overcome with non-nitrogenous supplemental energy or if increased energy as EAA is needed is unclear. We tested the effects of energy as EAA or carbohydrate, combined with an EAA-enriched whey protein, on post-exercise MPS (%/h) and whole-body protein turnover (g protein/240 min). METHODS: 17 adults (mean ± SD; age: 26 ± 6 y, BMI: 25 ± 3 kg/m 2 ) completed a randomized, parallel study including two 5-d energy conditions (BAL, energy balance; DEF, -30 ± 3% energy requirements) separated by ≥7 d. Volunteers consumed EAA-enriched whey with added EAA (+EAA; 304 kcal, 56 g protein, 48 g EAA, 17 g carbohydrate, 2 g fat; n = 8) or added carbohydrate (+CHO; 311 kcal, 34 g protein, 24 g EAA, 40 g carbohydrate, 2 g fat; n = 9) following exercise. MPS and whole-body protein synthesis (PS), breakdown (PB), and net balance (NET; PS-PB) were estimated postexercise with isotope kinetics. RESULTS: MPS rates were greater in +EAA (0.083 ± 0.02) than +CHO (0.059 ± 0.01; P = 0.015) during DEF, but similar during BAL ( P = 0.45) and across energy conditions within treatments ( P = 0.056). PS rates were greater for +EAA (BAL, 117.9 ± 16.5; DEF, 110.3 ± 14.8) than +CHO (BAL, 81.6 ± 8.0; DEF, 83.8 ± 5.9 g protein/240 min; both P < 0.001), and greater during BAL than DEF in +EAA ( P = 0.045). PB rates were less in +EAA (8.0 ± 16.5) than +CHO (37.8 ± 7.6 g protein/240 min; P < 0.001), and NET was greater in +EAA (106.1 ± 6.3) than +CHO (44.8 ± 8.5 g protein/240 min; P < 0.001). CONCLUSIONS: These data suggest that supplementing EAA-enriched whey protein with more energy as EAA, not carbohydrate, maintains postexercise MPS during energy deficit at rates comparable to those observed during energy balance.
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This study investigated the effects of EPO on hemoglobin (Hgb) and hematocrit (Hct), time trial (TT) performance, substrate oxidation, and skeletal muscle phenotype throughout 28 days of strenuous exercise. Eight males completed this longitudinal controlled exercise and feeding study using EPO (50 IU/kg body mass) 3×/week for 28 days. Hgb, Hct, and TT performance were assessed PRE and on Days 7, 14, 21, and 27 of EPO. Rested/fasted muscle obtained PRE and POST EPO were analyzed for gene expression, protein signaling, fiber type, and capillarization. Substrate oxidation and glucose turnover were assessed during 90-min of treadmill load carriage (LC; 30% body mass; 55 ± 5% VÌO2peak) exercise using indirect calorimetry, and 6-6-[2H2]-glucose PRE and POST. Hgb and Hct increased, and TT performance improved on Days 21 and 27 compared to PRE (p < 0.05). Energy expenditure, fat oxidation, and metabolic clearance rate during LC increased (p < 0.05) from PRE to POST. Myofiber type, protein markers of mitochondrial biogenesis, and capillarization were unchanged PRE to POST. Transcriptional regulation of mitochondrial activity and fat metabolism increased from PRE to POST (p < 0.05). These data indicate EPO administration during 28 days of strenuous exercise can enhance aerobic performance through improved oxygen carrying capacity, whole-body and skeletal muscle fat metabolism.
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Eritropoyetina , Ejercicio Físico , Músculo Esquelético , Oxidación-Reducción , Masculino , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Adulto , Eritropoyetina/metabolismo , Eritropoyetina/farmacología , Oxidación-Reducción/efectos de los fármacos , Ejercicio Físico/fisiología , Hemoglobinas/metabolismo , Hematócrito , Metabolismo Energético/efectos de los fármacos , Adulto Joven , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
Insulin insensitivity decreases exogenous glucose oxidation and metabolic clearance rate (MCR) during aerobic exercise in unacclimatized lowlanders at high altitude (HA). Whether use of an oral insulin sensitizer before acute HA exposure enhances exogenous glucose oxidation is unclear. This study investigated the impact of pioglitazone (PIO) on exogenous glucose oxidation and glucose turnover compared with placebo (PLA) during aerobic exercise at HA. With the use of a randomized crossover design, native lowlanders (n = 7 males, means ± SD, age: 23 ± 6 yr, body mass: 84 ± 11 kg) consumed 145 g (1.8 g/min) of glucose while performing 80 min of steady-state (1.43 ± 0.16 VÌo2 L/min) treadmill exercise at HA (460 mmHg; [Formula: see text] 96.6 mmHg) following short-term (5 days) use of PIO (15 mg oral dose per day) or PLA (microcrystalline cellulose pill). Substrate oxidation and glucose turnover were determined using indirect calorimetry and stable isotopes ([13C]glucose and 6,6-[2H2]glucose). Exogenous glucose oxidation was not different between PIO (0.31 ± 0.03 g/min) and PLA (0.32 ± 0.09 g/min). Total carbohydrate oxidation (PIO: 1.65 ± 0.22 g/min, PLA: 1.68 ± 0.32 g/min) or fat oxidation (PIO: 0.10 ± 0.0.08 g/min, PLA: 0.09 ± 0.07 g/min) was not different between treatments. There was no treatment effect on glucose rate of appearance (PIO: 2.46 ± 0.27, PLA: 2.43 ± 0.27 mg/kg/min), disappearance (PIO: 2.19 ± 0.17, PLA: 2.20 ± 0.22 mg/kg/min), or MCR (PIO: 1.63 ± 0.37, PLA: 1.73 ± 0.40 mL/kg/min). Results from this study indicate that PIO is not an effective intervention to enhance exogenous glucose oxidation or MCR during acute HA exposure. Lack of effect with PIO suggests that the etiology of glucose metabolism dysregulation during acute HA exposure may not result from insulin resistance in peripheral tissues.NEW & NOTEWORTHY Short-term (5 days) use of the oral insulin sensitizer pioglitazone does not alter circulating glucose or insulin responses to enhance exogenous glucose oxidation during steady-state aerobic exercise in young healthy men under simulated acute (8 h) high-altitude (460 mmHg) conditions. These results indicate that dysregulations in glucose metabolism in native lowlanders sojourning at high altitude may not be due to insulin resistance at peripheral tissue.
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Altitud , Estudios Cruzados , Ejercicio Físico , Glucosa , Hipoglucemiantes , Oxidación-Reducción , Pioglitazona , Humanos , Pioglitazona/administración & dosificación , Pioglitazona/farmacología , Masculino , Adulto Joven , Ejercicio Físico/fisiología , Adulto , Glucosa/metabolismo , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Hipoglucemiantes/farmacocinética , Tasa de Depuración Metabólica , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Insulina/sangre , Insulina/metabolismoRESUMEN
INTRODUCTION/PURPOSE: The effects of testosterone on energy and substrate metabolism during energy deficit are unknown. The objective of this study was to determine the effects of weekly testosterone enanthate (TEST; 200 mg·wk -1 ) injections on energy expenditure, energy substrate oxidation, and related gene expression during 28 d of energy deficit compared with placebo (PLA). METHODS: After a 14-d energy balance phase, healthy men were randomly assigned to TEST ( n = 24) or PLA ( n = 26) for a 28-d controlled diet- and exercise-induced energy deficit (55% below total energy needs by reducing energy intake and increasing physical activity). Whole-room indirect calorimetry and 24-h urine collections were used to measure energy expenditure and energy substrate oxidation during balance and deficit. Transcriptional regulation of energy and substrate metabolism was assessed using quantitative reverse transcription-polymerase chain reaction from rested/fasted muscle biopsy samples collected during balance and deficit. RESULTS: Per protocol design, 24-h energy expenditure increased ( P < 0.05) and energy intake decreased ( P < 0.05) in TEST and PLA during deficit compared with balance. Carbohydrate oxidation decreased ( P < 0.05), whereas protein and fat oxidation increased ( P < 0.05) in TEST and PLA during deficit compared with balance. Change (∆; deficit minus balance) in 24-h energy expenditure was associated with ∆activity factor ( r = 0.595), but not ∆fat-free mass ( r = 0.147). Energy sensing (PRKAB1 and TP53), mitochondria (TFAM and COXIV), fatty acid metabolism (CD36/FAT, FABP, CPT1b, and ACOX1) and storage (FASN), and amino acid metabolism (BCAT2 and BCKHDA) genes were increased ( P < 0.05) during deficit compared with balance, independent of treatment. CONCLUSIONS: These data demonstrate that increased physical activity and not exogenous testosterone administration is the primary determinate of whole-body and skeletal muscle metabolic adaptations during diet- and exercise-induced energy deficit.
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Metabolismo Energético , Testosterona , Masculino , Humanos , Oxidación-Reducción , Metabolismo Energético/fisiología , Ejercicio Físico/fisiología , PoliésteresRESUMEN
Posttranscriptional regulation by microRNA (miRNA) facilitates exercise and diet-induced skeletal muscle adaptations. However, the impact of diet on miRNA expression during postexercise recovery remains unclear. The objective of this study was to examine the effects of consuming carbohydrate or a nutrient-free control on skeletal muscle miRNA expression during 3 h of recovery from aerobic exercise. Using a randomized, crossover design, seven men (means ± SD, age: 21 ± 3 yr; body mass: 83 ± 13 kg; VÌo2peak: 43 ± 2 mL/kg/min) completed two-cycle ergometry glycogen depletion trials followed by 3 h of recovery while consuming either carbohydrate (CHO: 1 g/kg/h) or control (CON: nutrient free). Muscle biopsy samples were obtained under resting fasted conditions at baseline and at the end of the 3-h recovery (REC) period. miRNA expression was determined using unbiased RT-qPCR microarray analysis. Trials were separated by 7 days. Twenty-five miRNAs were different (P < 0.05) between CHO and CON at REC, with Let7i-5p and miR-195-5p being the most predictive of treatment. In vitro overexpression of Let7i-5p and miR-195-p5 in C2C12 skeletal muscle cells decreased (P < 0.05) the expression of protein breakdown (Foxo1, Trim63, Casp3, and Atf4) genes, ubiquitylation, and protease enzyme activity compared with control. Energy sensing (Prkaa1 and Prkab1) and glycolysis (Gsy1 and Gsk3b) genes were lower (P < 0.05) with Let7i-5p overexpression compared with miR-195-5p and control. Fat metabolism (Cpt1a, Scd1, and Hadha) genes were lower (P < 0.05) in miR-195-5p than in control. These data indicate that consuming CHO after aerobic exercise alters miRNA profiles compared with CON, and these differences may govern mechanisms facilitating muscle recovery.NEW & NOTEWORTHY Results provide novel insight into effects of carbohydrate intake on the expression of skeletal muscle microRNA during early recovery from aerobic exercise and reveal that Let7i-5p and miR-195-5p are important regulators of skeletal muscle protein breakdown to aid in facilitating muscle recovery.
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Glucógeno , MicroARNs , Adolescente , Adulto , Humanos , Masculino , Adulto Joven , Carbohidratos de la Dieta/farmacología , Carbohidratos de la Dieta/metabolismo , Ejercicio Físico/fisiología , Glucógeno/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Músculo Esquelético/metabolismoRESUMEN
BACKGROUND: Short-term starvation and severe food deprivation (FD) reduce dietary iron absorption and restricts iron to tissues, thereby limiting the amount of iron available for erythropoiesis. These effects may be mediated by increases in the iron regulatory hormone hepcidin; however, whether mild to moderate FD has similar effects on hepcidin and iron homeostasis is not known. OBJECTIVES: To determine the effects of varying magnitudes and durations of FD on hepcidin and indicators of iron status in male and female mice. METHODS: Male and female C57BL/6J mice (14 wk old; n = 170) were randomly assigned to consume AIN-93M diets ad libitum (AL) or varying magnitudes of FD (10%, 20%, 40%, 60%, 80%, or 100%). FD was based on the average amount of food consumed by the AL males or females, and food was split into morning and evening meals. Mice were euthanized at 48 h and 1, 2, and 3 wk, and hepcidin and indicators of iron status were measured. Data were analyzed by Pearson correlation and one-way ANOVA. RESULTS: Liver hepcidin mRNA was positively correlated with the magnitude of FD at all time points (P < 0.05). At 3 wk, liver hepcidin mRNA increased 3-fold with 10% and 20% FD compared with AL and was positively associated with serum hepcidin (R = 0.627, P < 0.0001). Serum iron was reduced by â¼65% (P ≤ 0.01), and liver nonheme iron concentrations were â¼75% greater (P ≤ 0.01) with 10% and 20% FD for 3 wk compared with AL. Liver hepcidin mRNA at 3 wk was positively correlated with liver Bmp6 (R = 0.765, P < 0.0001) and liver gluconeogenic enzymes (R = >0.667, P < 0.05) but not markers of inflammation (P > 0.05). CONCLUSIONS: FD increases hepcidin in male and female mice and results in hypoferremia and tissue iron sequestration. These findings suggest that increased hepcidin with FD may contribute to the disturbances in iron homeostasis with undernutrition.
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Hepcidinas , Inanición , Animales , Femenino , Privación de Alimentos , Hepcidinas/genética , Hormonas , Hierro , Hierro de la Dieta , Masculino , Ratones , Ratones Endogámicos C57BL , ARN MensajeroRESUMEN
MicroRNAs (miRNAs) regulate molecular processes governing muscle metabolism. Physical activity and energy balance influence both muscle anabolism and substrate metabolism, but whether circulating and skeletal muscle miRNAs mediate those effects remains unknown. This study assessed the impact of sustained physical activity with participants in energy balance (BAL) or deficit (DEF) on circulating and skeletal muscle miRNAs. Using a randomized cross-over design, 10 recreational active healthy males (mean ± SD, 22 ± 5 years, 87 ± 11 kg) completed 72 h of high aerobic exercise-induced energy expenditures in BAL (689 ± 852 kcal/day) or DEF (-2047 ± 920 kcal/day). Blood and muscle samples were collected under rested/fasted conditions before (PRE) and immediately after 120 min load carriage exercise bout at the end (POST) of the 72 h. Trials were separated by 7 days. Circulating and skeletal muscle miRNAs were measured using microarray RT-qPCR. Independent of energy status, 36 circulating miRNAs decreased (P < 0.05), while 10 miRNAs increased and three miRNAs decreased in skeletal muscle (P < 0.05) at POST compared to PRE. Of these, miR-122-5p, miR-221-3p, miR-222-3p and miR-24-3p decreased in circulation and increased in skeletal muscle. Two circulating (miR-145-5p and miR-193a-5p) and four skeletal muscle (miR-21-5p, miR-372-3p, miR-34a-5p and miR-9-5p) miRNAs had time-by-treatment effects (P < 0.05). These data suggest that changes in miRNA profiles are more sensitive to increased physical activity compared to energy status, and that changes in circulating miRNAs in response to high levels of daily aerobic exercise are not reflective of changes in skeletal muscle miRNAs. KEY POINTS: Circulating and skeletal muscle miRNA profiles are more sensitive to high levels of aerobic exercise-induced energy expenditure compared to energy status. Changes in circulating miRNA in response to high levels of daily sustained aerobic exercise are not reflective of changes in skeletal muscle miRNA.
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Ejercicio Físico , MicroARNs , Adulto , Estudios Cruzados , Metabolismo Energético , Ejercicio Físico/fisiología , Humanos , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Músculo Esquelético/metabolismo , Descanso/fisiología , Adulto JovenRESUMEN
BACKGROUND: The effects of low muscle glycogen on molecular markers of protein synthesis and myogenesis before and during aerobic exercise with carbohydrate ingestion is unclear. The purpose of this study was to determine the effects of initiating aerobic exercise with low muscle glycogen on mTORC1 signaling and markers of myogenesis. METHODS: Eleven men completed two cycle ergometry glycogen depletion trials separated by 7-d, followed by randomized isocaloric refeeding for 24-h to elicit low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate, 1.0 g/kg fat) glycogen. Participants then performed 80-min of cycle ergometry (64 ± 3% VO2peak) while ingesting 146 g carbohydrate. mTORC1 signaling (Western blotting) and gene transcription (RT-qPCR) were determined from vastus lateralis biopsies before glycogen depletion (baseline, BASE), and before (PRE) and after (POST) exercise. RESULTS: Regardless of treatment, p-mTORC1Ser2448, p-p70S6KSer424/421, and p-rpS6Ser235/236 were higher (P < 0.05) POST compared to PRE and BASE. PAX7 and MYOGENIN were lower (P < 0.05) in LOW compared to AD, regardless of time, while MYOD was lower (P < 0.05) in LOW compared to AD at PRE, but not different at POST. CONCLUSION: Initiating aerobic exercise with low muscle glycogen does not affect mTORC1 signaling, yet reductions in gene expression of myogenic regulatory factors suggest that muscle recovery from exercise may be reduced.
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Metabolismo de los Hidratos de Carbono , Ejercicio Físico/fisiología , Glucógeno/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Desarrollo de Músculos/fisiología , Músculo Esquelético/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Adulto , Biomarcadores/sangre , Metabolismo de los Hidratos de Carbono/genética , Estudios Cruzados , Ergometría/métodos , Glucógeno/deficiencia , Humanos , Masculino , Proteína MioD/metabolismo , Miogenina/metabolismo , Factor de Transcripción PAX7/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Factores de Tiempo , Transcripción Genética , Adulto JovenRESUMEN
BACKGROUND: The effects of ingesting varying essential amino acid (EAA)/protein-containing food formats on protein kinetics during energy deficit are undetermined. Therefore, recommendations for EAA/protein food formats necessary to optimize both whole-body protein balance and muscle protein synthesis (MPS) during energy deficit are unknown. We measured protein kinetics after consuming iso-nitrogenous amounts of free-form essential amino acid-enriched whey (EAA + W; 34.7 g protein, 24 g EAA sourced from whey and free-form EAA), whey (WHEY; 34.7 g protein, 18.7 g EAA), or a mixed-macronutrient meal (MEAL; 34.7 g protein, 11.4 g EAA) after exercise during short-term energy deficit. METHODS: Ten adults (mean ± SD; 21 ± 4 y; 25.7 ± 1.7 kg/m2) completed a randomized, double-blind crossover study consisting of three, 5 d energy-deficit periods (- 30 ± 3% of total energy requirements), separated by 14 d. Whole-body protein synthesis (PS), breakdown (PB), and net balance (NET) were determined at rest and in response to combination exercise consisting of load carriage treadmill walking, deadlifts, and box step-ups at the end of each energy deficit using L-[2H5]-phenylalanine and L-[2H2]-tyrosine infusions. Treatments were ingested immediately post-exercise. Mixed-muscle protein synthesis (mixed-MPS) was measured during exercise through recovery. RESULTS: Change (Δ postabsorptive + exercise to postprandial + recovery [mean treatment difference (95%CI)]) in whole-body (g/180 min) PS was 15.8 (9.8, 21.9; P = 0.001) and 19.4 (14.8, 24.0; P = 0.001) greater for EAA + W than WHEY and MEAL, respectively, with no difference between WHEY and MEAL. ΔPB was - 6.3 (- 11.5, - 1.18; P = 0.02) greater for EAA + W than WHEY and - 7.7 (- 11.9, - 3.6; P = 0.002) greater for MEAL than WHEY, with no difference between EAA + W and MEAL. ΔNET was 22.1 (20.5, 23.8; P = 0.001) and 18.0 (16.5, 19.5; P = 0.00) greater for EAA + W than WHEY and MEAL, respectively, while ΔNET was 4.2 (2.7, 5.6; P = 0.001) greater for MEAL than WHEY. Mixed-MPS did not differ between treatments. CONCLUSIONS: While mixed-MPS was similar across treatments, combining free-form EAA with whey promotes greater whole-body net protein balance during energy deficit compared to iso-nitrogenous amounts of whey or a mixed-macronutrient meal. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier no. NCT04004715 . Retrospectively registered 28 June 2019, first enrollment 6 June 2019.
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Aminoácidos Esenciales/metabolismo , Ejercicio Físico/fisiología , Nutrientes/metabolismo , Periodo Posprandial , Proteínas/metabolismo , Suero Lácteo/metabolismo , Adulto , Aminoácidos Esenciales/administración & dosificación , Aminoácidos Esenciales/sangre , Índice de Masa Corporal , Estudios Cruzados , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/metabolismo , Método Doble Ciego , Ingestión de Energía , Femenino , Alimentos Fortificados , Humanos , Insulina/sangre , Masculino , Comidas , Proteínas Musculares/biosíntesis , Nutrientes/administración & dosificación , Fenilalanina/administración & dosificación , Factores de Tiempo , Tirosina/administración & dosificación , Suero Lácteo/administración & dosificación , Suero Lácteo/química , Adulto JovenRESUMEN
Use of high-fat, ketogenic diets (KDs) to support physical performance has grown in popularity over recent years. While these diets enhance fat and reduce carbohydrate oxidation during exercise, the impact of a KD on physical performance remains controversial. The objective of this work was to assess the effect of KDs on physical performance compared with mixed macronutrient diets [control (CON)]. A systematic review of the literature was conducted using PubMed and Cochrane Library databases. Randomized and nonrandomized studies were included if participants were healthy (free of chronic disease), nonobese [BMI (kg/m2) <30], trained or untrained men or women consuming KD (<50 g carbohydrate/d or serum or whole-blood ß-hydroxybutyrate >0.5 mmol/L) compared with CON (fat, 12-38% of total energy intake) diets for ≥14 d, followed by a physical performance test. Seventeen studies (10 parallel, 7 crossover) with 29 performance (13 endurance, 16 power or strength) outcomes were identified. Of the 13 endurance-type performance outcomes, 3 (1 time trial, 2 time-to-exhaustion) reported lower and 10 (4 time trials, 6 time-to-exhaustion) reported no difference in performance between the KD compared with CON. Of the 16 power or strength performance outcomes, 3 (1 power, 2 strength) reported lower, 11 (4 power, 7 strength) no difference, and 2 (power) enhanced performance in the KD compared with the CON. Risk of bias identified some concern of bias primarily due to studies allowing participants to self-select diet intervention groups and the inability to blind participants to the study intervention. Overall, the majority of null results across studies suggest that a KD does not have a positive or negative impact on physical performance compared with a CON diet. However, discordant results between studies may be due to multiple factors, such as the duration consuming study diets, training status, performance test, and sex differences, which will be discussed in this systematic review.
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Dieta Cetogénica , Dieta Alta en Grasa , Ingestión de Energía , Ejercicio Físico , Femenino , Humanos , Estudios Longitudinales , MasculinoRESUMEN
BACKGROUND & AIMS: Consuming 0.10-0.14 g essential amino acids (EAA)/kg/dose (0.25-0.30 g protein/kg/dose) maximally stimulates muscle protein synthesis (MPS) during energy balance. Whether consuming EAA beyond that amount enhances MPS and whole-body anabolism following energy deficit is unknown. The aims of this study were to determine the effects of standard and high EAA ingestion on mixed MPS and whole-body protein turnover following energy deficit. DESIGN: Nineteen males (mean ± SD; 23 ± 5 y; 25.4 ± 2.7 kg/m2) completed a randomized, double-blind crossover study consisting of two, 5-d energy deficits (-30 ± 4% of total energy requirements), separated by 14-d. Following each energy deficit, mixed MPS and whole-body protein synthesis (PS), breakdown (PB), and net balance (NET) were determined at rest and post-resistance exercise (RE) using primed, constant L-[2H5]-phenylalanine and L-[2H2]-tyrosine infusions. Beverages providing standard (0.1 g/kg, 7.87 ± 0.87 g) or high (0.3 g/kg, 23.5 ± 2.54 g) EAA were consumed post-RE. Circulating EAA were measured. RESULTS: Postabsorptive mixed MPS (%/h) at rest was not different (P = 0.67) between treatments. Independent of EAA, postprandial mixed MPS at rest (standard EAA, 0.055 ± 0.01; high EAA, 0.061 ± 0.02) and post-RE (standard EAA, 0.055 ± 0.01; high EAA, 0.065 ± 0.02) were greater than postabsorptive mixed MPS at rest (P = 0.02 and P = 0.01, respectively). Change in (Δ postabsorptive) whole-body (g/180 min) PS and PB was greater for high than standard EAA [mean treatment difference (95% CI), 3.4 (2.3, 4.4); P = 0.001 and -15.6 (-17.8, -13.5); P = 0.001, respectively]. NET was more positive for high than standard EAA [19.0 (17.3, 20.7); P = 0.001]. EAA concentrations were greater in high than standard EAA (P = 0.001). CONCLUSIONS: These data demonstrate that high compared to standard EAA ingestion enhances whole-body protein status during underfeeding. However, the effects of consuming high and standard EAA on mixed MPS are the same during energy deficit. CLINICAL TRIAL REGISTRY: NCT03372928, https://clinicaltrials.gov.
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Aminoácidos Esenciales/administración & dosificación , Restricción Calórica , Proteínas Musculares/biosíntesis , Proteolisis , Adulto , Estudios Cruzados , Método Doble Ciego , Ingestión de Energía , Ejercicio Físico , Humanos , Masculino , Periodo Posprandial , Biosíntesis de Proteínas , Adulto JovenRESUMEN
BACKGROUND: Strenuous physical activity promotes inflammation and depletes muscle glycogen, which may increase the iron regulatory hormone hepcidin. Hepcidin reduces dietary iron absorption and may contribute to declines in iron status frequently observed following strenuous physical activity. OBJECTIVES: To determine the effects of strenuous physical activity on hepcidin and dietary iron absorption and whether energy deficit compared with energy balance modifies those effects. METHODS: This was a randomized, cross-over, controlled-feeding trial in healthy male subjects (n = 10, mean ± SD age: 22.4 ± 5.4 y, weight: 87.3 ± 10.9 kg) with sufficient iron status (serum ferritin 77.0 ± 36.7 ng/mL). Rest measurements were collected before participants began a 72-h simulated sustained military operation (SUSOPS), designed to elicit high energy expenditure, glycogen depletion, and inflammation, followed by a 7-d recovery period. Two 72-h SUSOPS trials were performed where participants were randomly assigned to consume either energy matched (±10%) to their individual estimated total daily energy expenditure (BAL) or energy at 45% of total daily energy expenditure to induce energy deficit (DEF). On the rest day and at the completion of BAL and DEF, participants consumed a beverage containing 3.8 mg of a stable iron isotope, and plasma isotope appearance was measured over 6 h. RESULTS: Muscle glycogen declined during DEF and was preserved during BAL (-188 ± 179 mmol/kg, P-adjusted < 0.01). Despite similar increases in interleukin-6, plasma hepcidin increased during DEF but not BAL, such that hepcidin was 108% greater during DEF compared with BAL (7.8 ± 12.2 ng/mL, P-adjusted < 0.0001). Peak plasma isotope appearance at 120 min was 74% lower with DEF (59 ± 38% change from 0 min) and 49% lower with BAL (117 ± 81%) compared with rest (230 ± 97%, P-adjusted < 0.01 for all comparisons). CONCLUSIONS: Strenuous physical activity decreases dietary iron absorption compared with rest. Energy deficit exacerbates both the hepcidin response to physical activity and declines in dietary iron absorption compared with energy balance. This trial was registered at clinicaltrials.gov as NCT03524690.
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Ingestión de Energía , Hepcidinas/metabolismo , Hierro de la Dieta/metabolismo , Adolescente , Adulto , Biomarcadores/sangre , Estudios Cruzados , Ejercicio Físico , Humanos , Inflamación/sangre , Inflamación/metabolismo , Isótopos de Hierro , Masculino , Músculo Esquelético/lesiones , Adulto JovenRESUMEN
BACKGROUND: Exogenous carbohydrate oxidation is lower during steady-state aerobic exercise in native lowlanders sojourning at high altitude (HA) compared to sea level (SL). However, the underlying mechanism contributing to reduction in exogenous carbohydrate oxidation during steady-state aerobic exercise performed at HA has not been explored. OBJECTIVE: To determine if alterations in glucose rate of appearance (Ra), disappearance (Rd) and metabolic clearance rate (MCR) at HA provide a mechanism for explaining the observation of lower exogenous carbohydrate oxidation compared to during metabolically-matched, steady-state exercise at SL. METHODS: Using a randomized, crossover design, native lowlanders (nâ¯=â¯8 males, mean⯱â¯SD, age: 23⯱â¯2â¯yr, body mass: 87⯱â¯10â¯kg, and VO2peak: SL 4.3⯱â¯0.2â¯L/min and HA 2.9⯱â¯0.2â¯L/min) consumed 145â¯g (1.8â¯g/min) of glucose while performing 80-min of metabolically-matched (SL: 1.66⯱â¯0.14 VÌO2 L/min 329⯱â¯28â¯kcal, HA: 1.59⯱â¯0.10 VÌO2 L/min, 320⯱â¯19â¯kcal) treadmill exercise in SL (757â¯mmHg) and HA (460â¯mmHg) conditions after a 5-h exposure. Substrate oxidation rates (g/min) and glucose turnover (mg/kg/min) during exercise were determined using indirect calorimetry and dual tracer technique (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion). RESULTS: Total carbohydrate oxidation was higher (Pâ¯<â¯0.05) at HA (2.15⯱â¯0.32) compared to SL (1.39⯱â¯0.14). Exogenous glucose oxidation rate was lower (Pâ¯<â¯0.05) at HA (0.35⯱â¯0.07) than SL (0.44⯱â¯0.05). Muscle glycogen oxidation was higher at HA (1.67⯱â¯0.26) compared to SL (0.83⯱â¯0.13). Total glucose Ra was lower (Pâ¯<â¯0.05) at HA (12.3⯱â¯1.5) compared to SL (13.8⯱â¯2.0). Exogenous glucose Ra was lower (Pâ¯<â¯0.05) at HA (8.9⯱â¯1.3) compared to SL (10.9⯱â¯2.2). Glucose Rd was lower (Pâ¯<â¯0.05) at HA (12.7⯱â¯1.7) compared to SL (14.3⯱â¯2.0). MCR was lower (Pâ¯<â¯0.05) at HA (9.0⯱â¯1.8) compared to SL (12.1⯱â¯2.3). Circulating glucose and insulin concentrations were higher in response carbohydrate intake during exercise at HA compared to SL. CONCLUSION: Novel results from this investigation suggest that reductions in exogenous carbohydrate oxidation at HA may be multifactorial; however, the apparent insensitivity of peripheral tissue to glucose uptake may be a primary determinate.
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Metabolismo de los Hidratos de Carbono , Ejercicio Físico/fisiología , Glucosa/farmacocinética , Hipoxia/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Estudios Cruzados , Prueba de Esfuerzo , Humanos , Hipoxia/patología , Masculino , Tasa de Depuración Metabólica , Oxidación-Reducción/efectos de los fármacos , Consumo de Oxígeno/fisiología , Adulto JovenRESUMEN
BACKGROUND: Initiating aerobic exercise with low muscle glycogen content promotes greater fat and less endogenous carbohydrate oxidation during exercise. However, the extent exogenous carbohydrate oxidation increases when exercise is initiated with low muscle glycogen is unclear. PURPOSE: Determine the effects of muscle glycogen content at the onset of exercise on whole-body and muscle substrate metabolism. METHODS: Using a randomized, crossover design, 12 men (mean⯱â¯SD, age: 21⯱â¯4 y; body mass: 83⯱â¯11â¯kg; VO2peak: 44⯱â¯3â¯mL/kg/min) completed 2â¯cycle ergometry glycogen depletion trials separated by 7-d, followed by a 24-h refeeding to elicit low (LOW; 1.5â¯g/kg carbohydrate, 3.0â¯g/kg fat) or adequate (AD; 6.0â¯g/kg carbohydrate, 1.0â¯g/kg fat) glycogen stores. Participants then performed 80â¯min of steady-state cycle ergometry (64⯱â¯3% VO2peak) while consuming a carbohydrate drink (95â¯g glucose +51â¯g fructose; 1.8â¯g/min). Substrate oxidation (g/min) was determined by indirect calorimetry and 13C. Muscle glycogen (mmol/kg dry weight), pyruvate dehydrogenase (PDH) activity, and gene expression were assessed in muscle. RESULTS: Initiating steady-state exercise with LOW (217⯱â¯103) or AD (396⯱â¯70; Pâ¯<â¯0.05) muscle glycogen did not alter exogenous carbohydrate oxidation (LOW: 0.84⯱â¯0.14, AD: 0.87⯱â¯0.16; Pâ¯>â¯0.05) during exercise. Endogenous carbohydrate oxidation was lower and fat oxidation was higher in LOW (0.75⯱â¯0.29 and 0.55⯱â¯0.10) than AD (1.17⯱â¯0.29 and 0.38⯱â¯0.13; all Pâ¯<â¯0.05). Before and after exercise PDH activity was lower (Pâ¯<â¯0.05) and transcriptional regulation of fat metabolism (FAT, FABP, CPT1a, HADHA) was higher (Pâ¯<â¯0.05) in LOW than AD. CONCLUSION: Initiating exercise with low muscle glycogen does not impair exogenous carbohydrate oxidative capacity, rather, to compensate for lower endogenous carbohydrate oxidation acute adaptations lead to increased whole-body and skeletal muscle fat oxidation.
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Carbohidratos/fisiología , Carbohidratos de la Dieta/metabolismo , Ejercicio Físico/fisiología , Grasas/metabolismo , Glucógeno/metabolismo , Músculo Esquelético/metabolismo , Adolescente , Adulto , Estudios Cruzados , Expresión Génica/fisiología , Humanos , Metabolismo de los Lípidos/fisiología , Masculino , Oxidación-Reducción , Transcripción Genética/fisiología , Adulto JovenRESUMEN
Ingesting protein and carbohydrate together during aerobic exercise suppresses the expression of specific skeletal muscle microRNA and promotes muscle hypertrophy. Determining whether there are independent effects of carbohydrate and protein on microRNA will allow for a clearer understanding of the mechanistic role microRNA serve in regulating skeletal muscle protein synthetic and proteolytic responses to nutrition and exercise. This study determined skeletal muscle microRNA responses to aerobic exercise with or without carbohydrate, and recovery whey protein (WP). Seventeen males were randomized to consume carbohydrate (CHO; 145 g; n = 9) or non-nutritive control (CON; n = 8) beverages during exercise. Muscle was collected before (BASE) and after 80 min of steady-state exercise (1.7 ± 0.3 VÌO2 L·min-1 ) followed by a 2-mile time trial (17.9 ± 3.5 min; POST), and 3-h into recovery after consuming WP (25 g; REC). RT-qPCR was used to determine microRNA and mRNA expression. Bioinformatics analysis was conducted using the mirPath software. Western blotting was used to assess protein signaling. The expression of six microRNA (miR-19b-3p, miR-99a-5p, miR-100-5p, miR-222-3p, miR-324-3p, and miR-486-5p) were higher (P < 0.05) in CHO compared to CON, all of which target the PI3K-AKT, ubiquitin proteasome, FOXO, and mTORC1 pathways. p-AKTThr473 and p-FOXO1Thr24 were higher (P < 0.05) in POST CHO compared to CON. The expression of PTEN was lower (P < 0.05) in REC CHO than CON, while MURF1 was lower (P < 0.05) POST CHO than CON. These findings suggest the mechanism by which microRNA facilitate skeletal muscle adaptations in response to exercise with carbohydrate and protein feeding is by inhibiting markers of proteolysis.
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Carbohidratos de la Dieta/farmacología , MicroARNs/metabolismo , Músculo Esquelético/metabolismo , Acondicionamiento Físico Humano/métodos , Proteolisis , Transducción de Señal , Carbohidratos de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/farmacología , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Humanos , Masculino , MicroARNs/genética , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Adulto JovenRESUMEN
Intramuscular factors that modulate fat-free mass (FFM) loss in lowlanders exposed to energy deficit during high-altitude (HA) sojourns remain unclear. Muscle inflammation may contribute to FFM loss at HA by inducing atrophy and inhibiting myogenesis via the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible protein 14 (Fn14). To explore whether muscle inflammation modulates FFM loss reportedly developing during HA sojourns, muscle inflammation, myogenesis, and proteolysis were assessed in 16 men at sea level (SL) and following 21 days of energy deficit (-1862 ± 525 kcal/days) at high altitude (HA, 4300 m). Total body mass (TBM), FFM, and fat mass (FM) were assessed using DEXA. Gene expression and proteolytic enzymatic activities were assessed in muscle samples collected at rest at SL and HA. Participants lost 7.2 ± 1.8 kg TBM (P < 0.05); 43 ± 30% and 57 ± 30% of the TBM lost was FFM and FM, respectively. Fn14, TWEAK, TNF alpha-receptor (TNFα-R), TNFα, MYOGENIN, and paired box protein-7 (PAX7) were upregulated (P < 0.05) at HA compared to SL. Stepwise linear regression identified that Fn14 explained the highest percentage of variance in FFM loss (r2 = 0.511, P < 0.05). Dichotomization of volunteers into HIGH and LOW Fn14 gene expression indicated HIGH lost less FFM and more FM (28 ± 28% and 72 ± 28%, respectively) as a proportion of TBM loss than LOW (58 ± 26% and 42 ± 26%; P < 0.05) at HA. MYOGENIN gene expression was also greater for HIGH versus LOW (P < 0.05). These data suggest that heightened Fn14 gene expression is not catabolic and may protect FFM during HA sojourns.
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Mal de Altura/metabolismo , Metabolismo Energético , Músculo Esquelético/metabolismo , Receptor de TWEAK/genética , Adulto , Humanos , Masculino , Miogenina/genética , Miogenina/metabolismo , Factor de Transcripción PAX7/genética , Factor de Transcripción PAX7/metabolismo , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/metabolismo , Receptor de TWEAK/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Pérdida de PesoRESUMEN
This study investigated how high-altitude (HA, 4300 m) acclimatization affected exogenous glucose oxidation during aerobic exercise. Sea-level (SL) residents (n = 14 men) performed 80-min, metabolically matched exercise ( VË O2 â¼ 1.7 L/min) at SL and at HA < 5 h after arrival (acute HA, AHA) and following 22-d of HA acclimatization (chronic HA, CHA). During HA acclimatization, participants sustained a controlled negative energy balance (-40%) to simulate the "real world" conditions that lowlanders typically experience during HA sojourns. During exercise, participants consumed carbohydrate (CHO, n = 8, 65.25 g fructose + 79.75 g glucose, 1.8 g carbohydrate/min) or placebo (PLA, n = 6). Total carbohydrate oxidation was determined by indirect calorimetry and exogenous glucose oxidation by tracer technique with 13C. Participants lost (P ≤ 0.05, mean ± SD) 7.9 ± 1.9 kg body mass during the HA acclimatization and energy deficit period. In CHO, total exogenous glucose oxidized during the final 40 min of exercise was lower (P < 0.01) at AHA (7.4 ± 3.7 g) than SL (15.3 ± 2.2 g) and CHA (12.4 ± 2.3 g), but there were no differences between SL and CHA. Blood glucose and insulin increased (P ≤ 0.05) during the first 20 min of exercise in CHO, but not PLA. In CHO, glucose declined to pre-exercise concentrations as exercise continued at SL, but remained elevated (P ≤ 0.05) throughout exercise at AHA and CHA. Insulin increased during exercise in CHO, but the increase was greater (P ≤ 0.05) at AHA than at SL and CHA, which did not differ. Thus, while acute hypoxia suppressed exogenous glucose oxidation during steady-state aerobic exercise, that hypoxic suppression is alleviated following altitude acclimatization and concomitant negative energy balance.
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BACKGROUND: Negative energy balance (EB) is common during military operations, diminishing body mass and physical performance. However, the magnitude of negative EB where performance would still be maintained is not well defined. OBJECTIVE: Our objective was to explore relationships between EB and physical performance during military operations and define an acceptable negative EB threshold where performance may be maintained. METHODS: A systematic search was performed for studies that measured EB and physical performance during military training. A total of 632 articles and technical reports were screened. Lower-body power and strength were the most common performance tests across investigations and were used as physical performance outcomes. Data were extracted from nine eligible studies containing 15 independent subgroups. Meta-regression assessed changes in performance in relation to study duration (days), average daily EB, and total EB (daily EB × duration). RESULTS: Changes in physical performance were not associated with average daily EB or training duration. Total EB was associated with changes in lower-body power (r2 = 0.764, P < 0.001) and strength (r2 = 0.836, P < 0.001) independently and combined (r2 = 0.454, P = 0.002). Predictive equations generated from the meta-regression indicated that, for a zero to small (2%) decline in performance, total EB should be limited to - 5686 to - 19,109 kcal, for an entire operation, whereas total EB of - 39,243 to - 59,377 kcal will result in moderate (7%) to large (10%) declines in performance. CONCLUSION: These data demonstrated that greater total negative EB is associated with declines in lower-body performance during military operations.
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Ingestión de Energía , Metabolismo Energético , Extremidad Inferior/fisiología , Personal Militar , Fuerza Muscular/fisiología , Equilibrio Postural/fisiología , Adolescente , Adulto , Ejercicio Físico/fisiología , Humanos , Persona de Mediana Edad , Aptitud Física/fisiología , Adulto JovenRESUMEN
Muscle loss at high altitude (HA) is attributable to energy deficit and a potential dysregulation of anabolic signaling. Exercise and protein ingestion can attenuate the effects of energy deficit on muscle at sea level (SL). Whether these effects are observed when energy deficit occurs at HA is unknown. To address this, muscle obtained from lowlanders ( n = 8 males) at SL, acute HA (3 h, 4300 m), and chronic HA (21 d, -1766 kcal/d energy balance) before [baseline (Base)] and after 80 min of aerobic exercise followed by a 2-mile time trial [postexercise (Post)] and 3 h into recovery (Rec) after ingesting whey protein (25 g) were analyzed using standard molecular techniques. At SL, Post, and REC, p-mechanistic target of rapamycin (mTOR)Ser2448, p-p70 ribosomal protein S6 kinase (p70S6K)Ser424/421, and p-ribosomal protein S6 (rpS6)Ser235/236 were similar and higher ( P < 0.05) than Base. At acute HA, Post p-mTORSer2448 and Post and REC p-p70S6KSer424/421 were not different from Base and lower than SL ( P < 0.05). At chronic HA, Post and Rec p-mTORSer2448 and p-p70S6KSer424/421 were not different from Base and lower than SL, and, independent of time, p-rpS6Ser235/236 was lower than SL ( P < 0.05). Post proteasome activity was lower ( P < 0.05) than Base and Rec, independent of phase. Our findings suggest that HA exposure induces muscle anabolic resistance that is exacerbated by energy deficit during acclimatization, with no change in proteolysis.-Margolis, L. M., Carbone, J. W., Berryman, C. E., Carrigan, C. T., Murphy, N. E., Ferrando, A. A., Young, A. J., Pasiakos, S. M. Severe energy deficit at high altitude inhibits skeletal muscle mTORC1-mediated anabolic signaling without increased ubiquitin proteasome activity.
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Karl, J. Philip, Renee E. Cole, Claire E. Berryman, Graham Finlayson, Patrick N. Radcliffe, Matthew T. Kominsky, Nancy E. Murphy, John W. Carbone, Jennifer C. Rood, Andrew J. Young, and Stefan M. Pasiakos. Appetite suppression and altered food preferences coincide with changes in appetite-mediating hormones during energy deficit at high altitude, but are not affected by protein intake. High Alt Med Biol. 19:156-169, 2018.-Anorexia and unintentional body weight loss are common during high altitude (HA) sojourn, but underlying mechanisms are not fully characterized, and the impact of dietary macronutrient composition on appetite regulation at HA is unknown. This study aimed to determine the effects of a hypocaloric higher protein diet on perceived appetite and food preferences during HA sojourn and to examine longitudinal changes in perceived appetite, appetite mediating hormones, and food preferences during acclimatization and weight loss at HA. Following a 21-day level (SL) period, 17 unacclimatized males ascended to and resided at HA (4300 m) for 22 days. At HA, participants were randomized to consume measured standard-protein (1.0 g protein/kg/d) or higher protein (2.0 g/kg/d) hypocaloric diets (45% carbohydrate, 30% energy restriction) and engaged in prescribed physical activity to induce an estimated 40% energy deficit. Appetite, food preferences, and appetite-mediating hormones were measured at SL and at the beginning and end of HA. Diet composition had no effect on any outcome. Relative to SL, appetite was lower during acute HA (days 0 and 1), but not different after acclimatization and weight loss (HA day 18), and food preferences indicated an increased preference for sweet- and low-protein foods during acute HA, but for high-fat foods after acclimatization and weight loss. Insulin, leptin, and cholecystokinin concentrations were elevated during acute HA, but not after acclimatization and weight loss, whereas acylated ghrelin concentrations were suppressed throughout HA. Findings suggest that appetite suppression and altered food preferences coincide with changes in appetite-mediating hormones during energy deficit at HA. Although dietary protein intake did not impact appetite, the possible incongruence with food preferences at HA warrants consideration when developing nutritional strategies for HA sojourn.