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Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients. The loss of nicotinamide adenine dinucleotide is reported to be associated with muscle mitochondrial dysfunction in murine cancer models. Here the authors show that niacin supplementation improves mitochondrial metabolism and reduces muscle wasting in mouse models of cachexia. [ABSTRACT FROM AUTHOR]

Purpose: Physique athletes engage in rigorous competition preparation involving intense energy restriction and physical training to enhance muscle definition. This study investigates hormonal changes and their physiological and performance impacts during such preparation.Participants included female (10 competing (COMP) and 10 non-dieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP participants were tested 23 weeks before (PRE), one week before (MID), and 23 weeks after the competition (POST). Non-dieting CTRL participants were tested at similar intervals. Measurements included body composition (DXA), muscle cross-sectional area (ultrasound), energy availability (EA) derived by subtracting exercise energy expenditure (EEE) from energy intake (EI) and dividing by fat-free mass (FFM), muscle strength, and various serum hormone concentrations (ACTH, cortisol, estradiol, FSH, IGF-1, IGFBP-3, insulin, and free and total testosterone and SHBG).During the diet, EA (p < 0.001), IGF-1 (p < 0.001), IGFBP-3 (p < 0.01), and absolute muscle strength (p < 0.01–0.001) decreased significantly in both sexes in COMP. Decreases in IGF-1 were also associated with higher loss in FFM. In males, testosterone (p < 0.01) and free testosterone (p < 0.05) decreased, while SHBG (p < 0.001) and cortisol (p < 0.05) increased. Insulin decreased significantly only in males (p < 0.001). Mood disturbances, particularly increased fatigue in males (p < 0.05), highlighted the psychological strain of competition preparation. All these changes were restored by increased EA during the post-competition recovery period.Significant reductions in IGF-1 and IGFBP-3 during competition preparation may serve as biomarkers for monitoring physiological stress. This study offers valuable insights into hormonal changes, muscle strength, and mood state during energy-restricted intense training.Methods: Physique athletes engage in rigorous competition preparation involving intense energy restriction and physical training to enhance muscle definition. This study investigates hormonal changes and their physiological and performance impacts during such preparation.Participants included female (10 competing (COMP) and 10 non-dieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP participants were tested 23 weeks before (PRE), one week before (MID), and 23 weeks after the competition (POST). Non-dieting CTRL participants were tested at similar intervals. Measurements included body composition (DXA), muscle cross-sectional area (ultrasound), energy availability (EA) derived by subtracting exercise energy expenditure (EEE) from energy intake (EI) and dividing by fat-free mass (FFM), muscle strength, and various serum hormone concentrations (ACTH, cortisol, estradiol, FSH, IGF-1, IGFBP-3, insulin, and free and total testosterone and SHBG).During the diet, EA (p < 0.001), IGF-1 (p < 0.001), IGFBP-3 (p < 0.01), and absolute muscle strength (p < 0.01–0.001) decreased significantly in both sexes in COMP. Decreases in IGF-1 were also associated with higher loss in FFM. In males, testosterone (p < 0.01) and free testosterone (p < 0.05) decreased, while SHBG (p < 0.001) and cortisol (p < 0.05) increased. Insulin decreased significantly only in males (p < 0.001). Mood disturbances, particularly increased fatigue in males (p < 0.05), highlighted the psychological strain of competition preparation. All these changes were restored by increased EA during the post-competition recovery period.Significant reductions in IGF-1 and IGFBP-3 during competition preparation may serve as biomarkers for monitoring physiological stress. This study offers valuable insights into hormonal changes, muscle strength, and mood state during energy-restricted intense training.Results: Physique athletes engage in rigorous competition preparation involving intense energy restriction and physical training to enhance muscle definition. This study investigates hormonal changes and their physiological and performance impacts during such preparation.Participants included female (10 competing (COMP) and 10 non-dieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP participants were tested 23 weeks before (PRE), one week before (MID), and 23 weeks after the competition (POST). Non-dieting CTRL participants were tested at similar intervals. Measurements included body composition (DXA), muscle cross-sectional area (ultrasound), energy availability (EA) derived by subtracting exercise energy expenditure (EEE) from energy intake (EI) and dividing by fat-free mass (FFM), muscle strength, and various serum hormone concentrations (ACTH, cortisol, estradiol, FSH, IGF-1, IGFBP-3, insulin, and free and total testosterone and SHBG).During the diet, EA (p < 0.001), IGF-1 (p < 0.001), IGFBP-3 (p < 0.01), and absolute muscle strength (p < 0.01–0.001) decreased significantly in both sexes in COMP. Decreases in IGF-1 were also associated with higher loss in FFM. In males, testosterone (p < 0.01) and free testosterone (p < 0.05) decreased, while SHBG (p < 0.001) and cortisol (p < 0.05) increased. Insulin decreased significantly only in males (p < 0.001). Mood disturbances, particularly increased fatigue in males (p < 0.05), highlighted the psychological strain of competition preparation. All these changes were restored by increased EA during the post-competition recovery period.Significant reductions in IGF-1 and IGFBP-3 during competition preparation may serve as biomarkers for monitoring physiological stress. This study offers valuable insights into hormonal changes, muscle strength, and mood state during energy-restricted intense training.Conclusion: Physique athletes engage in rigorous competition preparation involving intense energy restriction and physical training to enhance muscle definition. This study investigates hormonal changes and their physiological and performance impacts during such preparation.Participants included female (10 competing (COMP) and 10 non-dieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP participants were tested 23 weeks before (PRE), one week before (MID), and 23 weeks after the competition (POST). Non-dieting CTRL participants were tested at similar intervals. Measurements included body composition (DXA), muscle cross-sectional area (ultrasound), energy availability (EA) derived by subtracting exercise energy expenditure (EEE) from energy intake (EI) and dividing by fat-free mass (FFM), muscle strength, and various serum hormone concentrations (ACTH, cortisol, estradiol, FSH, IGF-1, IGFBP-3, insulin, and free and total testosterone and SHBG).During the diet, EA (p < 0.001), IGF-1 (p < 0.001), IGFBP-3 (p < 0.01), and absolute muscle strength (p < 0.01–0.001) decreased significantly in both sexes in COMP. Decreases in IGF-1 were also associated with higher loss in FFM. In males, testosterone (p < 0.01) and free testosterone (p < 0.05) decreased, while SHBG (p < 0.001) and cortisol (p < 0.05) increased. Insulin decreased significantly only in males (p < 0.001). Mood disturbances, particularly increased fatigue in males (p < 0.05), highlighted the psychological strain of competition preparation. All these changes were restored by increased EA during the post-competition recovery period.Significant reductions in IGF-1 and IGFBP-3 during competition preparation may serve as biomarkers for monitoring physiological stress. This study offers valuable insights into hormonal changes, muscle strength, and mood state during energy-restricted intense training. [ABSTRACT FROM AUTHOR]

Physical activity recommendations for public health include typically muscle-strengthening activities for a minimum of 2 days a week. The range of inter-individual variation in responses to resistance training (RT) aiming to improve health and well-being requires to be investigated. The purpose of this study was to quantify high and low responders for RT-induced changes in muscle size and strength and to examine possible effects of age and sex on these responses. Previously collected data of untrained healthy men and women (age 19 to 78 years, n = 287 with 72 controls) were pooled for the present study. Muscle size and strength changed during RT are 4.8 ± 6.1 % (range from −11 to 30 %) and 21.1 ± 11.5 % (range from −8 to 60 %) compared to pre-RT, respectively. Age and sex did not affect to the RT responses. Fourteen percent and 12 % of the subjects were defined as high responders (>1 standard deviation (SD) from the group mean) for the RT-induced changes in muscle size and strength, respectively. When taking into account the results of non-training controls (upper 95 % CI), 29 and 7 % of the subjects were defined as low responders for the RT-induced changes in muscle size and strength, respectively. The muscle size and strength responses varied extensively between the subjects regardless of subject's age and sex. Whether these changes are associated with, e.g., functional capacity and metabolic health improvements due to RT requires further studies. [ABSTRACT FROM AUTHOR]

This study investigated, in a multi-experiment design, the acute effects of milk protein ingestion, aging [50 young (approximately 26 years) vs. 45 older (approximately 61 years) men] and training state for the blood leukocyte and platelet responses acutely after a single bout of resistance exercise (RE). Moreover, basal effects of 21 weeks of resistance training (RT) were examined. The single bout of RE rapidly increased all blood leukocytes and platelets (P < 0.05). Protein ingestion before or before and after the RE bout did not have an effect on this response. However, younger men had a larger immediate exercise-induced response in leukocytes and platelets than older men. Basal fasting levels of leukocytes and platelets remained unchanged after 21 weeks of RT and this RT period did not change the acute RE-induced leukocyte and platelet response. The long-term RT was, however, able to slightly increase blood hematocrit. Blood platelet counts were consistently higher in the younger men when compared to the older men. Blood lymphopenia occurred only after a larger volume of exercise. In conclusion, the acute increase in blood leukocytes and platelets may be smaller in the older as when compared to the younger men. However, the number of immune cells and thus probably their function may not be affected by milk protein ingestion or months of resistance training. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the reliability and validity of the "panoramic" brightness mode ultrasonography (US) method to detect training-induced changes in muscle cross-sectional area (CSA) by comparison with results obtained using magnetic resonance imaging (MRI). Out of 27 young male volunteers, 20 subjects were assigned to training group and seven to non-training control group. Muscle CSAs of vastus lateralis were analyzed by MRI and US before and after 21 weeks of either heavy resistance training or control period. Measured by both the US and MRI, the resistance training induced significant increases (~13-14%, P < 0.001) in muscle CSA, whereas no changes were observed in control group. A high repeatability was found between the two consequent US measurements (intraclass correlation coefficient, ICC of 0.997) with standard error of measurement (SEM) of 0.38 cm(2) and smallest detectable difference of 1.1 cm(2). Validity of the US method against MRI in assessing CSA of VL produced ICC of 0.905 and SEM of 0.87 cm(2) with high limits of agreement analyzed by Bland and Altman method. However, the MRI produced systematically (10 +/- 4%, P < 0.01) larger CSA values than the US method. The US showed high agreement against MRI in detecting changes in muscle CSA (ICC of 0.929, SEM of 0.94 cm(2)). The results of this study showed that the panoramic US method provides repeatable measures of a muscle CSA although MRI produced larger absolute CSA values. Moreover, this US method detects training-induced changes in muscle CSA with a comparable degree of precision to MRI. [ABSTRACT FROM AUTHOR]

We examined the acute effects of a 1-h strength training session (STS) on plasma amino acid concentration following orally ingestion of leucine, branched-chain amino acids (BCAAs) or glutamine in nine physically active men who participated in double-blinded and randomised experiments. The subjects took placebo, leucine, BCAAs, or glutamine capsules (50 mg/kg) in either rest (REST) or STS condition. Blood samples were taken before and at 30, 60, 90, and 120 min after the beginning of the treatment and they were assayed for plasma amino acids with HPLC. Following both leucine and BCAA ingestion the peak concentration of leucine was similar at rest (524 +/- 46 and 530 +/- 29 nmol/ml, respectively) and similar after STS (398 +/- 43 and 387 +/- 46 nmol/ml, respectively) but the rest and STS concentrations differed from each other (P < 0.01-0.001). The modelled polynomial data for the leucine treatment showed that the peak concentration of leucine occurred at 67 min at rest and at 90 min in STS (difference between REST and STS: P = 0.012). For the BCAA treatment the polynomial data showed that the peak concentration of leucine occurred at 72 min at rest and at 78 min in STS (P = 0.067). The peak concentration of glutamine was similar in both rest and STS condition and occurred at 60 min at rest and at 57 min in STS. In conclusion, 1-h of STS slows the increase in the peak concentration of plasma leucine similarly after oral ingestion of leucine or BCAAs but after oral ingestion of glutamine it has no slowing effect on glutamine concentration. [ABSTRACT FROM AUTHOR]

Myostatin decreases muscle mass and this is accomplished, in part, by inhibiting muscle satellite cell proliferation and differentiation by regulating the expression of cell cycle-related proteins (e.g. p21 and cdk2) and myogenic regulatory factors (e.g. myogenin and MyoD). The purpose of this investigation was to determine whether protein ingestion before and after a resistance exercise (RE) bout affects myostatin and cell cycle-related gene expression. Strength-trained middle-aged to older men were divided into a protein group (61.4 +/- 4.3 years, n = 9) or a placebo group (62.1 +/- 4.2 years, n = 9). Muscle biopsies from the vastus lateralis muscle were taken at rest and 1 and 48 h after a 5 x 10 repetition leg press RE bout. Protein (15 g whey) or non-caloric placebo was taken immediately before and after the RE bout. mRNA expression levels of myostatin and related genes (AcvrIIb, FLRG, p21, p27, cdk2, myogenin and MyoD) were determined by Taqman probe-based real-time RT-PCR and normalized to GAPDH mRNA. Myostatin mRNA decreased after a RE bout, but only in the placebo group (P < or = 0.05). Conversely, myostatin-binding protein FLRG and cell-cycle kinase cdk2 mRNA increased only in the protein group (P < or = 0.05). p21 mRNA was increased at 1 h post-RE in placebo (P < or = 0.05) and tended to be increased in the protein group (P = 0.08). Myostatin, its binding protein and cell cycle-related gene expressions are affected by single RE bout and these responses are further modified by whey protein intake. Therefore, controlling nutrition intake is important when studying gene expression responses to exercise. [ABSTRACT FROM AUTHOR]

This study investigated the effects of a heavy resistance exercise session (RES) with the oral daytime ingestion of melatonin on the physiological responses and acute performance. In a randomized and double-blind controlled study 10 healthy male subjects undertook an 80 min intensive hypertrophic RES for major muscles of the lower and upper extremities. The subjects were studied on two occasions receiving either melatonin (6 mg) or placebo (6 mg) in random order 60 min before each RES. Blood samples were taken from an antecubital vein both in fasting conditions in the morning and before RES (pre 60 min, pre 0 min), during RES (middle) and after RES (post 0 min, post 15 min, post 30 min, post 60 min). Maximal jumping ability and maximal strength in bench press and squat were measured before and immediately after RES in which there were no differences between the melatonin and placebo groups. The serum melatonin concentration increased significantly ( P<0.05–0.001) in the melatonin group following oral ingestion of melatonin and was elevated at every time point after that. The concentration reached a peak value of 1171.3±235.2 pg/ml in 60 min at pre 0. Serum melatonin increased slightly but significantly ( P<0.05) also in the placebo group just before RES, in the middle of RES and after RES (post 0, post 15). There were large differences ( P<0.01–0.001) in the serum melatonin concentration between the groups at all time points. There were no differences in the growth hormone (GH), testosterone and cortisol peak concentrations at any time points between the groups but the area under the curve of GH during RES ( P<0.01) and during the 60 min after RES ( P<0.05) was lower in the melatonin condition. In conclusion, the present findings give evidence that oral ingestion of melatonin (6 mg) during daytime with heavy resistance exercise may slightly decrease GH concentrations. On the other hand, it seems that melatonin administration during daytime does not have any acute (1–2 h) effects either on the maximal jumping ability or on the maximal strength. [ABSTRACT FROM AUTHOR]