Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects

Background: Reactive oxygen species (ROS) regulate glucose metabolism (GM) in skeletal muscle by improving the translocation of GLUT4. Antioxidant supplementation could block this physiological effect, altering glucose signaling during exercise. However, there is limited evidence in humans on whether antioxidant intake affects GM. Therefore, we aimed to determine the effect of an antioxidant cocktail (AOC) on GM at rest and during metabolic challenges. Methods: Ten healthy male subjects received AOC supplementation (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of α-lipoic acid) or placebo (2.000 mg of talc) before two trials conducted 7 days apart. Trial 1: AOC 120 and 90 minutes before an endurance exercise (EEX) bout at 60 % of maximal oxygen uptake (VO2max); Trial 2: AOC 120 and 90 minutes before an oral glucose tolerance test (OGTT; 75 g glucose). Measurements of gas exchange and capillary blood samples were collected every 15 minutes during both trials. Results: AOC supplementation increased resting glucose levels (p<0.05). During Trial 1 (EEX), the AOC increased carbohydrate oxidation (CHOox) (p= 0.03), without effect in glucose blood levels. During Trial 2 (OGTT), the AOC supplementation had no significant effect on GM parameters. Conclusion: Acute supplementation with AOC increased resting glucose levels and CHOox during EEX in healthy subjects, with no effect on GM during the OGTT.

Antecedentes: Las especies reactivas de oxígeno (ROS) regulan el metabolismo de la glucosa (GM) en el músculo esquelético al mejorar la translocación de GLUT4. La suplementación con antioxidantes podría bloquear este efecto fisiológico, alterando la señalización de la glucosa durante el ejercicio. Sin embargo, existe evidencia limitada en humanos sobre si la ingesta de antioxidantes afecta el GM. Por lo tanto, nuestro objetivo fue determinar el efecto de un cóctel de antioxidantes (AOC) en el GM en reposo y durante desafíos metabólicos. Métodos: Sujetos sanos (sexo masculino; n= 10) recibieron suplementos de AOC (1.000 mg de vitamina C, 600 UI de vitamina E y 600 mg de ácido α-lipoico) o placebo (2.000 mg de talco) previo a dos pruebas realizadas con 7 días de diferencia. Prueba 1: AOC 120 y 90 minutos antes de una serie de ejercicio de resistencia (EEX) al 60% del consumo máximo de oxígeno (VO2max); prueba 2: AOC 120 y 90 minutos antes de una prueba de tolerancia oral a la glucosa (OGTT; 75 g de glucosa). Se obtuvieron datos de intercambio de gaseoso y muestras de sangre capilar cada 15 minutos durante ambas pruebas. Resultados: la suplementación con AOC aumentó los niveles de glucosa en reposo (p<0,05). Durante la prueba 1 (EEX), el AOC aumentó la oxidación de carbohidratos (CHOox) (p= 0,03), sin efecto en los niveles de glucosa en sangre. Durante la prueba 2 (OGTT), la suplementación con AOC no tuvo un efecto significativo en los parámetros de GM. Conclusión: Una suplementación aguda con AOC aumentó los niveles de glucosa en reposo y la CHOox durante EEX en sujetos sanos, sin efecto sobre el GM durante la OGTT.

Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux

Background Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. Methods We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. Results UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. Conclusions Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.

Cholic and deoxycholic acids induce mitochondrial dysfunction, impaired biogenesis and autophagic flux in skeletal muscle cells

Background Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia. Methods We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. Results DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. Conclusion Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.

Association of maximal voluntary isometric handgrip strength with age, gender and handedness in older people / Fuerza de agarre isométrica máxima en relación a la edad, sexo y dominancia de mano

ABSTRACT Background: Maximal voluntary isometric handgrip strength (MVIHS) is influenced by age, sex, and handedness. Aim: To assess the association of MVIHS with age, sex, and handedness in older adults. Material and Methods: MVIHS was measured using a digital dynamometer in 60 men and 60 women aged 73 ± 6 years. Weight, height and handedness were also recorded. For analysis purposes, participants were divided into two age groups (65 to 70.9 years of age and ≥ 71 years). Results: A negative correlation was observed between age and MVIHS in the non-dominant (r = −0.65 and −0.59 in men and women, respectively) and dominant hands (r = −0.71 and −0.64 in men and women, respectively). When age and MVIHS were correlated in the group aged 65-70 years, a significant correlation was observed in the non-dominant (r = −045 and −0.61 in men and women, respectively) and dominant hands (r = −0.47 and −0.64 in men and women, respectively). In the group aged ≥ 71 years, a stronger correlation with age was also observed in the non-dominant (r = −0.92 and −0.90 in men and women, respectively) and dominant hands (r = −0.95 and −0.90 in men and women, respectively). MVIHS was 2.8 to 8.9% lower in the non-dominant than in the dominant hand in all age groups. MVIHS was lower in women than in men in both age groups. Conclusions: MVIHS declines with age (especially after 71 years of age), is higher in men than women, and higher in the dominant than the non-dominant hand.

Antecedentes: La fuerza de agarre isométrica voluntaria máxima (FAIVM) puede verse influenciada por la edad, el sexo y la dominancia. Objetivo: Describir la FAIVM y su relación con la edad, el sexo y la dominancia en adultos mayores. Material y Métodos: La FAIVM, la masa corporal, la talla, y la dominancia fueron medidas mediante protocolos estandarizados en 60 hombres e igual número de mujeres que fueron divididos en dos grupos acorde a su edad (65 a 70,9 años, y ≥ 71 años, respectivamente). Resultados: Se observó una correlación entre la edad y la FAIVM de mano no-dominante (hombres: r = −0,65; mujeres: r = −0,59) y dominante (hombres: r = −0,71; mujeres: r = −0,64). Al correlacionar la FAIVM y la edad en el grupo de 65-70 años, una correlación significativa fue observada en la mano no-dominante (hombres, r = −0,45; mujeres, r = −0,61) y mano dominante (hombres, r = −0,47; mujeres, r = −0,64). En el grupo ≥ 71 años, la edad tuvo una mayor correlación con la FAIVM de la mano no-dominante (hombres, r = −0,92; mujeres, r = −0,90) y mano dominante (hombres, r = −0,95; mujeres, r = −0,90). Comparada con la mano dominante, la mano no-dominante presentó menores valores de FAIVM en todos los grupos, variando entre −2,8 a −8,9%. Comparadas con los hombres, las mujeres presentaron menor FAIVM en mano dominante y no-dominante, en ambos grupos de edad. Conclusión: La FAIVM disminuye con la edad, especialmente desde los 71 años; es mayor en hombres comparados con mujeres y es mayor en mano dominante comparada con mano no-dominante.

Diferencias de composición corporal y condición fisica en educadoras de párvulo con normopeso, sobrepeso y obesidad: estudio transversal / Diffences of body max index, body composition, and fitness in normo weight, overweight and obese kindergarten teachers: cross-sectional study

Objective: To describe body mass index (BMI), body composition, basal metabolic rate, physical condition and the relation-ship between them in Chilean kindergarten teachers. Subjects and Methods: 46 teachers (age 39,5 ± 8,6) from the Bio Bio province(Chile) were weighed and heighted and BMI was measured. In addition, fat mass, lean and bone percentages, basal metabolic rate, muscular strength and cardiorespiratory fitness were measured. Results: The teachers had an average BMI of overweight (26,7 ± 3,5) and a high fat percentage (35,1 ± 5,9) according to national reference values. 58,7%were overweight and moderately obese. When teachers were compared according BMI, teachers with obesity had on average a higher percentage of fat mass (P =,000), less lean mass (P = ,000), took more time to complete the UKK test (P = ,035 ) and had a lower vo2max (P = ,001) than normal weight teachers. BMI had a negative association in relation to scores of the physical performance test. Conclusions: The overweight/obese teachers had more fat mass, reduced muscle mass and had worse results on fitness tests. Condition worrying thinking about the important role in modeling healthy habits to preschoolers.

Objetivo: Describir el índice de masa corporal (IMC), composición corporal, la tasa metabólica basal, condición física y su relación en educadoras de párvulos chilenas. Sujetos y Métodos: 46 educadoras (edad 39,5±8,6) de la provincia de Bio-Bio (Chile) se pesaron, midieron y se obtuvo su IMC. Se midió el porcentaje de masa grasa, magra, ósea, tasa metabólica basal, fuerza explosiva y capacidad cardiorrespiratoria. Resultados: Las educadoras tuvieron un IMC promedio de sobrepeso (26,7±3,5) y un elevado porcentaje de grasa (35,1±5,9) de acuerdo a referencias nacionales. El 58,7% de ellas presentó sobrepeso y obesidad moderada. Cuando se comparó por IMC, las educadoras con obesidad presentaron en promedio un mayor porcentaje de masa grasa (P =,000), menor de masa magra (P =,000), demoraron más tiempo en terminar el UKK test (P =,035) y tuvieron un menor vo2max (P =,001) en comparación a las educadoras con normopeso. El IMC se asoció negativamente a los test de rendimiento físico. Conclusión: Las maestras con sobrepeso/obesidad presentaron más masa grasa, menos masa muscular y peores resultados en las pruebas de condición física. Condición preocupante pensando en su importante rol modelando hábitos de vida saludables en los prescolares.

¿Pueden ocho semanas de ejercicio físico combinado normalizar marcadores metabólicos de sujetos hiperglicémicos y dislipidémicos? / Eight weeks of combined high intensity intermittent exercise normalized altered metabolic parameters in women

Background: Short term physical training programs may improve insulin resistance and hyperglycemia. Aim: To assess the effects of eight weeks of combined exercise program on serum lipids and glycemic level in women with hyperglycemia and hypercholesterolemia. Patients and Methods: Ten healthy women, nine women with hyperglycemia, ten with hypercholesterolemia and nine with hyperglycemia/hypercholesterolemia were studied. Participants were subjected to eight weeks into a program of combined physical exercise (high intensity interval + resistance training). Results: Fasting glycemia decreased by 12 and 14% in hyperglycemic and hyperglycemic/hypercholesterolemic participants, respectively. Serum insulin decreased in all groups in a range from 27 to 37%. HOMA IR for insulin resistance decreased similarly. A significant decrease in TC and TG was observed only in those altered baseline subjects. Conclusions: Eight weeks of combined physical exercise had a favorable effect on insulin resistance in this group of women.