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- Azzinnari, M, et al.
(author)
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Efectos del ejercicio en la señalización de NF-kB durante la restricción calórica severa
- 2017
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Conference paper (peer-reviewed)abstract
- El sobrepeso y la obesidad, en crecimiento en todo el mundo, se asocian con una alta tasa de mortalidad e morbilidad[1,2]. La causa principal que conduce a éstas condiciones patológicas es un balance energético positivo sostenido a largo plazo, debido a la inactividad física y la ingesta calórica excesiva[3]. Por lo tanto, ejercicio físico y restricción calórica podrían ser dos estratégias eficaces para prevenir y contrastar el excesivo acumulo de grasa corporal que caracteriza estas patologías. Sin embargo, durante dietas muy bajas en calorías (<800 Kcal/día) se pierde no solo masa grasa sino también masa muscular, reportando efectos negativos para la salud[4]. En dichas condiciones, el ejercicio físico permite preservar masa muscular de manera local y dosis-dependiente, mientras la ingestión de proteínas no ejerce particulares efectos protectivos sobre el tejido contráctil[5]. Los mecanismos moleculares implicados en la preservación de la masa muscular inducida por el ejercicio durante este tipo de dietas no han sido definidos claramente. NF-kB es un factor de transcripción cuya activación provoca atrofia muscular, y su bloqueo puede parcialmente limitar este fenomeno[6]. NF-kB se ha mostrado activado de manera aguda por el ejercicio y la restricción calorica, sin embargo no ha sido definida su respuesta a la restricción calórica en conjunción con el ejercicio prolongado de baja intensidad. Además, cuando los niveles basales de NF-kB son altos, el ejercicio no parece aumentar ulteriormente su señalización[7]. Por las razones presentadas, NF-kB podría desempeñar un rol en la preservación de masa magra inducida por el ejercicio durante la restricción calórica.El objetivo del estudio es establecer la respuesta de NF-kB a la restricción calórica severa en conjunción con el ejercicio prolongado de baja intensidad. Las hipótesis fueron las siguientes: 1) la restricción calórica severa activaría la via de NF-kB y 2) dicha activación será atenuada por el ejercicio de manera local y dosis-dependiente.15 sujetos con sobrepeso y obesidad fueron sometidos a tres fases experimentales: fase 1, en la que la dieta y el nivel de actividad física de los participantes fue monitorizado durante una semana (PRE); fase 2, caracterizada por cuatro días de ejercicio prolongado y de restricción calórica severa (RCE); fase 3, caracterizada por tres días de ejercicio reducido y una dieta isoenergética (DC). Durante la fase 2, los sujetos ingeriron hidratos de carbono o proteínas (0.8 g/kg peso corporal/día; 320 kcal/día) y hicieron 45 minutos de pedaleo con un solo miembro superior (15% Ppeak) seguidos de 8 horas de caminata (4.5 km/h; 35 km/día). Las biopsias musculares fueron recogidas de ambos los deltoides y del vasto lateral en la fase 1 y después de la fase 2 y 3. Mediante Western blot, se determinó la expresión de NF-κB p105, NF-κB p50, la fosforilación de la Serina 32/36 de IκBα e IκBα total. La composición corporal se midió mediante DXA. Estadística: ANOVA para medidas repetidas.Durante los 4 días de restricción calórica severa el deficit energético fue de 5500 Kcal. Después de la fase 2 los sujetos perdieron menos masa magra en los miembros inferiores y en el brazo ejercitado respecto al brazo de control: 57% (P<0.05) y 29% (P=0.05), respectivamente. Tras la fase 2 y 3, el contenido de p105 y de p50 fue menor en los miembros inferiores respecto a los superiores: efecto extremidad P=0.003 y P=0.024 para p105 y p50, respectivamente. Tras la fase 3, la fosforilación de la Serina 32/36 de IkBα aumentó únicamente en las piernas, mientras la expresión total IkBα fue mayor solo en los miembros ejercitados (P<0.05).El ejercicio físico atenuó la activación de la señalización de NF-kB durante 4 días de restricción calórica severa, limitando el incremento de la expresión de p50 y p105, que resultó más baja después de la fase 2 y la fase 3 en los miembros inferiores respecto a los miembros superiores, posiblemente debido a la mayor cantidad de ejercicio a la que fueron sometidos. Además, la expresión total de IkBα fue más alta tras la fase 3 solo en los miembros ejercitados, indicando una posible inhibición de la vía de NF-kB inducida por el ejercicio. Por lo tanto, dado la menor activación de la señalización de NF-kB en los miembros que perdieron menor masa muscular, los resultados sugieren que los efectos protectores del ejercicio físico sobre el tejido contráctil podrían ser mediados a una menor activación de la señalización de NF-kB.El ejercicio físico desempeña una función preservadora sobre la masa muscular durante la restricción calórica severa. La preservación de masa muscular es dosis-dependiente (a mayor volumen, mayor preservación) y está mediada, al menos parcialmente, por una menor activación de la señalización por NF-kB.1.Hill, J. O., H. R. Wyatt, et al. (2012). Circulation 126(1): 126-132.2.Di Angelantonio, E., N. Bhupathiraju Sh, et al. (2016). Lancet 388(10046): 776-786. 3.Chaston, T. B., J. B. Dixon, et al. (2007). Int J Obes (Lond) 31(5): 743-750. 4.Calbet, J. A., J. G. Ponce-Gonzalez, et al. (2017). Front Physiol (Accepted, In press).5.Cai, D., J. D. Frantz, et al. (2004). Cell 119(2): 285-298.6.Tantiwong, P., K. Shanmugasundaram, et al. (2010). Am J Physiol Endocrinol Metab 299(5): E794-801.7.NCD-RisC (2016). Lancet 387(10026): 1377-1396.
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| 4. |
- Cardinale, Daniele A., 1982-, et al.
(author)
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Muscle mass and inspired oxygen influence oxygen extraction at maximal exercise : role of mitochondrial oxygen affinity.
- 2019
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In: Acta Physiologica. - : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 225:1
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Journal article (peer-reviewed)abstract
- AIM:We examined the Fick components together with mitochondrial O2 affinity (p50mito ) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER).METHODS:Seven individuals performed two incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and two on a one-legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP-stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibers and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery.RESULTS:The ex vivo p50mito increased from 0.06±0.02 to 0.17±0.04 kPa with varying substrate supply and O2 flux rates from 9.84±2.91 to 16.34±4.07 pmol O2 ·s-1 ·μg-1 respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery, and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time.CONCLUSION:O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise. This article is protected by copyright. All rights reserved.
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| 5. |
- Larsen, Filip J, 1977-, et al.
(author)
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Mitochondrial oxygen affinity increases after sprint interval training and is related to the improvement in peak oxygen uptake.
- 2020
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In: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 229:3
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Journal article (peer-reviewed)abstract
- AIMS: The body responds to exercise training by profound adaptations throughout the cardiorespiratory and muscular systems, which may result in improvements in maximal oxygen consumption (VO2 peak) and mitochondrial capacity. By convenience, mitochondrial respiration is often measured at supra-physiological oxygen levels, an approach that ignores any potential regulatory role of mitochondrial affinity for oxygen (p50mito ) at physiological oxygen levels.METHODS: In this study, we examined the p50mito of mitochondria isolated from the Vastus lateralis and Triceps brachii in 12 healthy volunteers before and after a training intervention with 7 sessions of sprint interval training using both leg cycling and arm cranking. The changes in p50mito were compared to changes in whole-body VO2 peak.RESULTS: We here show that p50mito is similar in isolated mitochondria from the Vastus (40 ± 3.8 Pa) compared to Triceps (39 ± 3.3) but decreases (mitochondrial oxygen affinity increases) after 7 sessions of sprint interval training (to 26 ± 2.2 Pa in Vastus and 22 ± 2.7 Pa in Triceps, both p<0.01). The change in VO2 peak modeled from changes in p50mito was correlated to actual measured changes in VO2 peak (R2 =0.41, p=0.002).CONCLUSION: Together with mitochondrial respiratory capacity, p50mito is a critical factor when measuring mitochondrial function, it can decrease with sprint interval training and should be considered in the integrative analysis of the oxygen cascade from lung to mitochondria.
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| 6. |
- Martin-Rincon, M., et al.
(author)
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Exercise mitigates the loss of muscle mass by attenuating the activation of autophagy during severe energy deficit
- 2019
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 11:11
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Journal article (peer-reviewed)abstract
- The loss of skeletal muscle mass with energy deficit is thought to be due to protein breakdown by the autophagy-lysosome and the ubiquitin-proteasome systems. We studied the main signaling pathways through which exercise can attenuate the loss of muscle mass during severe energy deficit (5500 kcal/day). Overweight men followed four days of caloric restriction (3.2 kcal/kg body weight day) and prolonged exercise (45 min of one-arm cranking and 8 h walking/day), and three days of control diet and restricted exercise, with an intra-subject design including biopsies from muscles submitted to distinct exercise volumes. Gene expression and signaling data indicate that the main catabolic pathway activated during severe energy deficit in skeletal muscle is the autophagy-lysosome pathway, without apparent activation of the ubiquitin-proteasome pathway. Markers of autophagy induction and flux were reduced by exercise primarily in the muscle submitted to an exceptional exercise volume. Changes in signaling are associated with those in circulating cortisol, testosterone, cortisol/testosterone ratio, insulin, BCAA, and leucine. We conclude that exercise mitigates the loss of muscle mass by attenuating autophagy activation, blunting the phosphorylation of AMPK/ULK1/Beclin1, and leading to p62/SQSTM1 accumulation. This includes the possibility of inhibiting autophagy as a mechanism to counteract muscle loss in humans under severe energy deficit.
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| 7. |
- MARTIN-RINCON, M, et al.
(author)
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Upregulation of nicotinamide n-methyltransferase in skeletal muscle following prolongedexercise and caloric restriction
- 2017
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In: 22nd Annual Congress of the European College of Sport Science. - Cologne, Germany : DTP Publishing. - 9783981841404 ; , s. 186-
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Conference paper (peer-reviewed)abstract
- IntroductionExpression of Nicotinamide (NA) N-methyltransferase (NNMT), the enzyme responsible for the methylation of NA to methylnicotinamide (MNA), is reduced in obese and diabetic mice. In rodent liver, NNMT activity and plasma MNA levels are increased after 90min of swimming.NNMT knockdown in mice white adipose tissue increases energy expenditure, suggesting a protective role against diet-induced obesity and type-2 diabetes. The role that NNMT plays in human metabolism remains unknown. Thus, the aims of the study were 1) to determine in human skeletal muscle (sm) whether NNMT is upregulated by prolonged exercise and 2) to ascertain whether the expression of NNMT in sm is influenced by severe energy deficit.MethodsFifteen overweight men underwent to 4 days of caloric restriction (CR) (0.8 g/kg BW/day) in combination with prolonged exercise (PE) (8h walking + 45min single-arm cranking/day). Three sm biopsies (exercised/non exercised arm and one leg) were obtained before (PRE), after (PE+CR) and following 3 days of control diet (isoenergetic) and reduced exercise (CD) to measure the expression of key metabolic genes (e.g. PDK4, CPT2, PFKFB3, NNMT) (microarray), NNMT protein expression (WB) and circulating plasma MNA levels (LC-MS). Maximal fat oxidation (MFO) (indirect calorimetry) and body composition (DEXA) were measured. ANOVA repeated-measures was used.ResultsDuring PE+CR the energy deficit was 5000 kcal/d reducing fat mass by 2.8 (PE+CR) and 3.8 kg (CD). MFO was increased. CPT2, PDK4, PFKFB3 genes (CHO-to-fat metabolic shift) were differentially expressed (FDR<5%) in at least one sm. Compared to PRE, after CD, NNMT gene expression was upregulated in all sm (~3-5 fold). Protein NNMT increased ~13-fold (p<0.001), ~9-fold (p<0.01) and ~5-fold (p<0.001) for non-exercised and exercised arm (45min/day) and leg (8h/day), respectively. Circulating levels of MNA were augmented two-fold. The increase in NNMT expression from PRE to CD was associated with the increase in MFO (r=0.37, p=0.01,n=45).DiscussionThis findings reveal that NNMT is upregulated in human sm in response to a severe energy deficit, with a simultaneous increase of MNA plasma levels. However, this response was attenuated in the exercised sm. NNMT may have a role in facilitating fat oxidation. Caloric restriction elicits increased sirtuins expression and activity, coupled with the NAD+ breakdown into NA. Overexpression of NNMT probably prevents accumulation of NA, which would otherwise inhibit the sirtuins. Our data suggest sm as a plausible source of MNA, which may act as a myokine with a role in the adaptation to starvation.
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- Zinner, Christoph, et al.
(author)
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Sprint interval training or arms and legs elevates peak VO2 and improves arm exercise economy
- 2015
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Conference paper (peer-reviewed)abstract
- IntroductionInterval cycle sprint training (SIT) has been shown to improve anaerobic capacity, VO2max and biomarkers of muscle oxidative capacity in as little as 2 weeks in previously untrained adults. The present study was designed to characterize and compare systemic VO2 and exercise performance after SIT engaging the arms and legs. MethodsSixteen healthy, untrained men (23.9 ± 3.7 yrs; 183.8 ± 6.8 cm; 80.3 ± 14.1 kg) performed six sessions of 4-6x30 sec all-out sprints with the legs then arms (or vice versa) separated by a 1-h recovery over an 11-day period. Limb-specific VO2peak, anaerobic capacity (2x30-sec Wingate tests with 4 min of recovery), a 4-min submaximal work economy test, and a 5-min all-out time trial (TT) were conducted before and after the training program. Muscle biopsies (from the m. vastus lateralis and m. triceps brachii) were taken before and after the training period. ResultsVO2peak increased by 10.6% and 5.9% with arm and leg training, respectively (p<0.05), with the increase in the arms significantly greater than in the legs (p=0.02). Work economy was improved for the arms (-9.8%, p<0.05), but not for the legs (-0.9%). Mean power during the TT rose by 13.5% for the arms and 11.8% for the legs (p<0.05). Peak power output and mean power during the two Wingate tests were elevated in both the arms (PPO: 6.7% (p<0.01) and 13.3% (p<0.01); MPO: 6.1% (p<0.01) and 8.4% (p<0.01)) and legs (PPO: 3.1% (p=0.07) and 7.1% (p=0.02); MPO: 3.3% (p<0.01) and 5.6% (p<0.01)). The activity of 3-hydroxyacyl-CoA dehydrogenase (HAD) and levels of muscle glycogen were unchanged in both limbs. DiscussionSprint interval training with arm or leg cycling exercise increased peak pulmonary VO2 during their respective modes over an 11-day training period with a greater increase in the arms. Sprint performance rose to a similar extent in both extremities, yet work economy was improved only in the arms. These findings suggest some limb-specific responsiveness to SIT training.
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